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Vol. 66. Issue 1.
Pages 55.e1-55.e11 (January 2013)
Special article
DOI: 10.1016/j.rec.2012.12.001
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Summary of the Clinical Studies Reported in the Annual Scientific Sessions of the American Heart Association (Los Angeles, CA, USA, november 3-7, 2012)
Resumen de los ensayos clínicos presentados en las Sesiones Científicas Anuales de la American Heart Association (Los Ángeles, California, Estados Unidos, 3-7 de noviembre de 2012)
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Corresponding author: Revista Española de Cardiología, Sociedad Española de Cardiología, Ntra. Sra. de Guadalupe 5-7, 28028 Madrid, España.
, Antoni Bayes-Genisa, Leopoldo Pérez de Islaa, Juan Sanchisa, Magda Herasb
a Associate Editor, Revista Española de Cardiología
b Editor in Chief, Revista Española de Cardiología
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Following its policy of disseminating scientific information to the cardiology community, 1–8Revista Española de Cardiología offers a selection of the most relevant studies presented at the Scientific Sessions of the American Heart Association (Los Angeles, California, United States, November 3-7, 2012), specifically the Late-Breaking Clinical Trials.

A summary of each selected study is presented, briefly outlining the objectives, methods, and results based on what was presented orally or simultaneously published in scientific journals in electronic format. Given that most of these studies have not yet been published in their final version, the information offered should be interpreted as preliminary.

Summary by TopicPractice Implications for Coronary Artery Disease and Venous Thromboembolism

Aspirin for the Prevention of Recurrent Venous Thromboembolism After a First Unprovoked Event: Results of the ASPIRE Randomized Controlled Trial.

A Randomized Trial of Bedside Platelet-Function Monitoring to Adjust Antiplatelet Therapy versus Standard of Care in Patients Undergoing Drug-Eluting Stent Implantation: The ARCTIC Study.

First Large-scale Platelet-Function Evaluation in an Acute Coronary Syndromes Trial: The TRILOGY ACS Platelet-function Substudy.

Results of the Trial to Assess Chelation Therapy.

Main Results of the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) Trial.

Health Economics and Quality of Life in Contemporary Trials

Prospective Evaluation of Outcomes With Stress Perfusion Imaging versus Stress Wall Motion Imaging During Dobutamine or Exercise Echocardiography.

Economic Outcomes of Percutaneous Coronary Intervention Performed at Sites With and Without On-site Cardiac Surgery.

Quality-of-Life Outcomes in the Trial to Assess Chelation Therapy (TACT).

Cost-Effectiveness of percutaneous coronary intervention with Drug- Eluting Stents versus Bypass Surgery for Patients with Diabetes and Multivessel Coronary Artery Disease: Results from the FREEDOM Trial.

Treatments for Prevention of Cardiovascular Events: a Population Perspective

Omega-3 Fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation: Results of a double-blind randomized clinical trial (FORWARD).

Fish Oil for the Prevention of Post-operative Atrial Fibrillation: The Omega-3. Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Trial.

A Randomize d Trial of a Multivitamin in the Prevention of Cardiovascular Disease in Men: The Physicians’ Health Study II.

Use of a Multidrug Pill in Re ducing Cardiovascular Events (UMPIRE).

Novel Treatments for Managing Lipids Disorders

Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD): Interim Results from a Phase 2, Randomized, Double-blind, Placebo-Controlled Trial.

Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects (GAUSS): Interim Results from a Randomized, Double-blind, Placebo-Controlled Study.

Effects of 12 Weeks of Treatment with RN316 (PF-04950615), a Humanize d IgG2Δa Monoclonal Antibody Binding Proprotein Convertase Subtilisin Kexin Type 9, in Hypercholesterolemic Subjects on High- and Maximal Dose Statins.

Effects of the Cholesteryl Ester Transfer Protein Inhibitor Dalcetrapib in Patients with Recent Acute Coronary Syndrome.

Cell-based Therapies for Myocardial Regeneration

Results of the Swiss Multicenter Intracoronary Stem Cells Study in Acute Myocardial Infarction (Swiss AMI) Trial.

The Effect of Timing of Stem-cell Delivery Following Acute Myocardial Infarction: The NHLBI and CCTRN TIME Trial.

Randomize d Comparison of Allogeneic versus Autologous Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy.

Ef f ect of Car diac St em Cells in P atients With Isc hemic Cardiomyopathy: Interim Results of the SCIPIO Trial Up to 2 Years After Therapy.

Management of Left Ventricle Dysfunction: Devices and Drugs

MADIT Randomize d Trial to Re duce Inappropriate Therapy (MADIT-RIT).

Biventricular versus Right Ventricular Pacing in Patients With Left Ventricular Dysfunction and Atrioventricular Block (BLOCK HF Study).

Pilot Trial of Two Levels of Hypothermia in Comatose Survivors of Out-of-hospital Cardiac Arrest.

The Relaxin in Acute Heart Failure (RELAX-AHF) Trial.

Cardiorenal Rescue Study in Acute Decompensated Heart Failure: Results of CARRESS-HF, for the Heart Failure Clinical Research Network.

Practice implications for Coronary Artery Disease and Venous ThromboembolismAspirin for the Prevention of Recurrent Venous Thromboembolism After a First Unprovoked Event: Results of the ASPIRE Randomized Controlled Trial9Presenter: Tim Brighton, Sydney, Australia.

Background. Patients who have had a first episode of unprovoked venous thromboembolism have a high risk of recurrence after anticoagulants are discontinue d. Aspirin may b e effective in preventing a recurrence of venous thromboembolism.

Methods. We randomly assigned 822 patients who had completed initial anticoagulant therapy after a first episode of unprovoked venous thromboembolism to receive aspirin, at a dose of 100mg daily, or placebo for up to 4 years. The primary outcome was a recurrence of venous thromboembolism.

Results. During a median follow-up of 37.2 months, venous thromboembolism recurred in 73 of 411 patients assigned to placebo and in 57 of 411 assigned to aspirin (a rate of 6.5% per year vs 4.8% per year; hazard ratio [HR] with aspirin, 0.74; 95% confidence interval [CI], 0.52 to 1.05; P=.09). Aspirin re duce d the rate of the two prespecified secondary composite outcomes: the rate of venous thr omboembolism, my ocar dial inf ar ction (MI), stroke, or cardiovascular death was reduced by 34% (a rate of 8% per year with placebo vs 5.2% per year with aspirin; HR with aspirin, 0.66; 95% CI, 0.48 to 0.92; P=.01), and the rate of venous thromboembolism, MI, stroke, major bleeding, or death from any cause was reduced by 33% (HR=0.67; 95% CI, 0.49 to 0.91; P=.01). There was no significant between-group difference in the rates of major or clinically relevant nonmajor bleeding episodes (rate of 0.6% per year with placebo vs 1.1% per year with aspirin, P=.22) or serious adverse events.

Conclusions. In this study, aspirin, as compared with placebo, did no t signif icantl y r e duce the rate of r ecurr ence of v enous thromboembolism but resulted in a significant reduction in the rate of major vascular events, with improved net clinical benefit. These results substantiate earlier evidence of a therapeutic benefit of aspirin when it is given to patients after initial anticoagulant therapy for a first episode of unprovoked venous thromboembolism.

A Randomized Trial of Bedside Platelet Function Monitoring to Adjust Antiplatelet Therapy versus Standard of Care in Patients Undergoing Drug Eluting Stent Implantation: The ARCTIC Study10Presenter: Gilles Montalescot, Paris, France.

Background. Patients’ responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronar y stenting by individualizing therapy.

Methods. We randomly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring, with drug adjustment in patients who had a poor response to antiplatelet therapy, or to a conventional strategy without monitoring and drug adjustment. The primary end point was the composite of death, MI, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later.

Results. In the monitoring group, high platelet reactivity in patients taking clopidogrel (34.5% of patients) or aspirin (7.6%) led to the administration of an additional bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure. The primary end point occurred in 34.6% of the patients in the monitoring group, as compared with 31.1% of those in the conventional-treatment group (HR=1.13; 95% CI, 0.98 to 1.29; P=.10). The main secondary end point, stent thrombosis or any urgent revascularization, occurred in 4.9% of the patients in the monitoring group and 4.6% of those in the conventional-treatment group (HR=1.06; 95% CI, 0.74 to 1.52; P=.77). The rate of major bleeding events did not differ significantly between groups.

Conclusions. This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring.

First Large-scale Platelet-function Evaluation in an Acute Coronary Syndromes Trial: The TRILOGY ACS Platelet-function Sub-study11Presenter: Paul A. Gurbel, Baltimore, Maryland, United States.

Background. The relationship of platelet function testing measurements with outcomes in patients with acute coronary syndromes (ACS) initially managed medically without revascularization is unknown. The objective of the study was to characterize the differences and evaluate clinical outcomes associated with platelet reactivity among patients with ACS treated with clopidogrel or prasugrel.

Methods. Patients with medically managed unstable angina or non–ST-segment elevation MI were enrolled in the TRILOGY ACS trial (20 08 to 2011) comparing clopidogrel versus prasugrel. Of 9326 participants, 27.5% were included in a platelet function substudy: 1286 treated with prasugrel and 1278 treated with clopidogrel. Aspirin with either prasugrel (10 or 5mg/d) or clopidogrel (75mg/d) was given. Patients aged 75 or older, or those younger than 75 but who weighed less than 60kg, received a maintenance dose of prasugrel (5mg). The main outcome was platelet reactivity, measured in P2Y12 reaction units (PRUs) at baseline, at 2hours, and at 1, 3, 6, 12, 18, 24, and 30 months after randomization. The primary efficacy end point was a composite of cardiovascular death, MI, or stroke through 30 months.

Results. Among participants younger than 75 years and weighing 60kg or more, the median PRU values at 30 days were 64 (interquartile range [IQR], 33-128) in the prasugrel group versus 200 (IQR, 141-260) in the clopidogrel group (P<.001), a difference that persisted through all subsequent time points. For participants younger than 75 years and weighing less than 60kg, the median 30-day PRU values were 139 (IQR, 86-203) for the prasugrel group versus 209 (IQR, 148-283) for the clopidogrel group (P<.001), and for participants 75 years or older, the median PRU values were 164 (IQR, 105-216) for the prasugrel group versus 222 (IQR, 148-268) for the clopidogrel group (P<.001). At 30 months the rate of the primary efficacy end point was 17.2% (160 events) in the prasugrel group versus 18.9% (180 events) in the clopidogrel group (P=.29). There were no significant differences in the continuous distributions of 30-day PRU values for participants with a primary efficacy end point event after 30 days (n=214) compared with participants without an event (n=1794; P=.07) and no significant relationship between the occurence of the primary efficacy end point and continuous PRU values (adjusted HR [HR] for increase of 60 PRUs, 1.03; 95% CI, 0.96-1.11; P=.44). Similar findings were observed with 30-day PRU cut points used to define high on-treatment platelet reactivity—PRU more than 208 (adjusted HR, 1.16; 95% CI, 0.89-1.52, P=.28) and PRU more than 230 (adjusted HR, 1.20; 95% CI, 0.90-1.61; P=.21).

Conclusions. Among patients with ACS, without ST-segment ele vation, and initially manage d without re vascularization, prasugrel was associate d with lower platelet reactivity than clopidogrel, irrespective of age, weight, and dose. Among those in the platelet substudy, no significant differences existed between prasugrel versus clopidogrel in the occurrence of the primary efficacy end point through 30 months and no significant association existed between platelet reactivity and occurrence of ischemic outcomes.

Results of the Trial to Assess Chelation Therapy12Presenter: Gervasio A. Lamas, Miami, Florida, United States.

Background. According to reports from the CDC, the use of chelation therapy with disodium ethylene diamine tetra acetic acid (EDTA) therapy to treat atherosclerosis is increasing in the United States. Whether or not it is safe or effective cannot be determined based on current clinical data. The purpose of the study was to evaluate the safety and effectiveness of an EDTA chelation solution versus placebo in post-MI patients.

Methods. This randomized study included 1708 post-MI patients (≥6 weeks post-MI) who also received standard care, aged ≥50 years with an average follow-up of 4 years. The intervention consisted of 40 infusions of an EDTA-chelation solution and of an oral, high-dose, multivitamin and mineral supplement versus placebo. The primary composite end point was mortality (all-cause), MI, stroke, coronary revascularization, or angina hospitalization. Secondary end points were composite CV death, nonfatal MI, nonfatal stroke

Results. Composite endpoints: 18% re duction EDTA versus placebo (P=.035); Analysis by subgroups: Diabetes: 39% reduction in composite endpoints versus placebo (P=.002); Nondiabetics: 0.04% reduction versus placebo (P=.725); Anterior MI: 37% reduction versus placebo.

Conclusions. Post-MI patients who received chelation therapy had fewer clinical events compared to placebo. Two groups benefited most: diabetics and those who had experienced an anterior MI. Additional research is needed to confirm these findings and to understand the mechanisms of action for the benefits seen in this trial.

Main Results of the Future Revascularization Evaluation in Patients With Diabetes mellitus: Optimal Management of Multivessel Disease (FREEDOM) Trial13Presenter: Valentin Fuster, New York, United States.

Bac kgr ound. In some r andomize d trials com paring revascularization strategies for patients with diabetes, coronary-artery bypass graf ting (CABG) has had a b etter outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease (CAD).

Methods. In this randomized trial, we assigned patients with diabetes and multivessel CAD to undergo either PCI with drug- eluting stents or CABG. The patients were followed for a minimum of 2 years (median among survivors, 3.8 years). All patients were prescrib e d currently recommende d me dical therapies for the control of low-density lipoprotein cholesterol, systolic blood pressure (BP), and glycated hemoglobin. The primary outcome measure was a composite of death from any cause, nonfatal MI, or nonfatal stroke.

Results. From 2005 through 2010, we enrolled 1900 patients at 140 international centers. The patients’ mean age was 63.1±9.1 years, 29% were women, and 83% had 3-vessel disease. The primary outcome occurred more frequently in the PCI group (P=.005), with 5-year rates of 26.6% in the PCI group and 18.7% in the CABG group. The benefit of CABG was driven by differences in rates of both MI (P<.001) and death from any cause (P=.049). Stroke was more frequent in the CABG group, with 5-year rates of 2.4% in the PCI group and 5.2% in the CABG group (P=.03).

Conclusions. For patients with diabetes and advanced CAD, CABG was superior to PCI in that it significantly reduced rates of death and MI, with a higher rate of stroke.

Health Economics and Quality of Life in Contemporary TrialsProspective Evaluation of Outcomes With Stress Perfusion Imaging Versus Stress Wall Motion Imaging During Dobutamine or Exercise Echocardiography14Presenter: Thomas R. Porter, Omaha, Nebraska, United States.

Bac kgr ound. Re tr ospectiv e s tudies ex amining r eal-time myocardial contrast echocardiography (RTMCE) during an intravenous (iv) microbubble infusion have improved the detection of CAD during exercise or pharmacologic stress echocardiography (SE). These studies were performed with experienced reviewers in selected patients. The purpose of this study was to prospectively compare the predictive value of RTMCE with conventional stress echo (CSE), where contrast is used only for the Food and Drug Administration indication of left ventricular opacification.

Methods. A total of 2063 patients with intermediate pre-test probability undergoing either dobutamine or exercise SE were prospectively randomized to either RTMCE or CSE as their imaging modality during SE. A continuous infusion of Definity (Lantheus Me dical) was use d for all RTMCE studies to examine for both myocardial perfusion and wall motion, while Definity was used for CSE only when endocardial border delineation was inadequate (46% of all studies). RTMCE was performed with real-time pulse sequence schemes (mechanical index <0.25; frame rate 20-25Hz). Studies were interpreted immediately by either an experienced reviewer (R1; n=1257) in perfusion imaging, or 4 Level III reviewers with basic training in perfusion imaging (R2; n=806).

Results. Follow-up was available in 2014 patients (median follow up 2.5 years). Mean age was 59±13 years (53% women). Patients randomized to RTMCE had slightly lower ejection fraction and higher frequency of prior revascularization (both P<.005). Abnormal RTMCE studies were more frequent than abnormal CSE (P<.001), and more frequently abnormal in a multivessel territory (P<.005). Overall event-free survival (EFS) in those with positive or negative studies was not different between CSE and RTMCE. The predictive value of a positive study for both CSE and RTMCE was significant for R1 but not for R2 reviewers.

Conclusions. Abnormal studies are more frequently detected with RTMCE. Although the predictive value of SE with contrast is improved with experienced contrast users, the overall positive or negative predictive value of a dobutamine or exercise SE, when performed with RTMCE versus CSE in general practice, is not different.

Economic Outcomes of Percutaneous Coronary Intervention Performed at Sites With and Without On-site Cardiac Surgery15Presenter: Eric L. Eisenstein, Durham, North Carolina, United States.

Background. The aim was to compare costs of PCI between centers without and with on-site cardiac surgery.

Methods. The study groups consisted of 14 149 (no on-site surgery centers) and 4718 patients (on-site surgery centers). Cost data were collected from inpatient bills and estimated the costs for outpatient cardiac procedures, inpatient stays, emergency-department visits, physician visits, and ambulance transportation costs.

Results. Patients undergoing PCI at centers with cardiac surgery on-site had slightly lower average costs over 9 months than similar patients treated at centers without surgery, but the difference in cost was statistically nonsignificant. The costs of the procedures at the centers without surgery were statistically sensitive to variations in annual PCI volume, with higher-volume centers generally incurring lower per-procedure costs. Most important, the study requirement that PCI patients at the nonsurgery centers be treated in the intensive-care unit after their procedure had a “dramatic” effect on the costs, even though patients treated at the nonsurgery cent ers had a short er length of hospitalization on average. Periprocedural costs were greater in the low-volume centers than at high-volume centers, especially among the centers with no on-site cardiac surgery. These differences were related not to differences in implant costs but to the total costs in the cath lab. No patients at centers with on-site surgery were required to receive postprocedural care in an ICU or CCU.

Conclusions. Although PCI costs slightly less in centers with cardiac-surgery capabilities than in centers without them, the difference appears to be related to center volume rather than the direct benefits of on-site emergency surgical backup.

Quality-of-life Outcomes in the Trial to Assess Chelation Therapy (TACT)16Presenter: Daniel B. Mark, Durham, North Carolina, United States.

Background. This study examined quality of life outcomes in the Trial to Assess Chelation Therapy (TACT).

Methods. This is a NIH-funde d, randomize d, double-blind, placebo-controlled, 2 × 2 factorial trial comparing 40 infusions of an ethylene diamine tetra-acetic (EDTA)-chelation solution with placebo in patients with CAD. In a random sample of the 50% of patients in TACT (n=911 of a total 1708 patients), quality of life was assessed at baseline and at 6, 12, and 24 months. The quality-of-life tests included the Medical Outcomes Study Short Form-36 (SF-36), including its Mental Health Inventory-5 (MHI-5) component that assessed anxiety and depression. The MHI-5 along with the Duke Activity Status Index (DASI), a measure of cardiac functional status, were “co-principal end points” for the analysis. Also included were the Seattle Angina Questionnaire (SAQ) Anginal Frequency and Quality of Life subscales.

Results. Chelation therapy had almost no effect on standard measurements of quality of life, compared to placebo. The exception was slight improvement in self-reported anginal symptoms with chelation therapy at 1 year (P=.016). However, according to the SAQ, about 80% of the patients had no anginal symptoms at baseline, so it was a small minority of the total population.

Conclusions. Obtained improvements in quality of life were very small and not associated with chelation. The quality-of-life results do not support clinical results.

Cost-effectiveness of Percutaneous Coronary Intervention With Drug-eluting Stents versus Bypass Surgery for Patients With Diabetes and Multivessel Coronary Artery Disease: Results From the FREEDOM Trial17Presenter: Elizabeth A. Magnuson, Kansas City, Missouri, United States.

Background. Although earlier studies have suggested that PCI could be more cost-effective than CABG, there has not been a study that compares the cost-effectiveness of PCI with drug-eluting stents (DES-PCI) t o C ABG in diab e tic patients having multi v essel revascularization. The purpose of the study was to evaluate cost- effectiveness of CABG versus DES-PCI for diabetic patients having multivessel revascularization. These results will compliment the clinical results of the FREEDOM trial.

Methods. Diabetic patients (n=1900) with multivessel CAD were randomized to either DES-PCI or CABG. Follow-up: 5 years. The primary endpoint was incremental cost-effectiveness ratio (ICER), or cost per quality-adjusted life year gained (QALY).

Results. Initial costs: CABG cost $8622/patient more than DES-PCI (P<.001). Five-year costs: CABG cost $3641/patient and yielded 0.031

QALY improvement and a ICER gain of $116 699/QALY. Lifetime cost- effectiveness ratio: 0.66 gain in QALY, CABG costs of $5392/patient (ICER gain of $8132/QALY for CABG).

Conclusions. For diabetic patients with multivessel disease, initial costs were higher for CABG than for PCI because of hospital stay and early complications. Total 5-year costs for CABG were also higher, but the follow-up costs for PCI were greater. However, based on lifetime projections, CABG was found to be more cost-effective compared to DES-PCI.

Treatments for Prevention of Cardiovascular Events: A Population PerspectiveOmega-3 fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation: Results of a Double-blind Randomized Clinical Trial (FORWARD)18Presenter: Alejandro Macchia, Santa Maria Imbaro, Italy.

Background. Atrial fibrillation (AF) is associated with increased risk of death, thromboembolic complications, and decreased quality of life. Despite this burden, pharmacologic agents for prevention of AF in patients who achieved normal sinus rhythm are of limited utility, mostly because of serious and frequent side effects. Thus, the availability of safer and more effective drugs may reduce the burden of disease. The aim of the s tudy was to t e s t the ef f icacy of pharmacologic supplementation with 1g daily of n-3 fatty acids (PUFA) for the maintenance of normal sinus rhythm in patients with previous AF.

Methods. FORWARD randomize d patients with at least 2 symptomatic episodes of documented AF in the past 6 months or successful electrical or pharmacological cardioversion for persistent AF performed in the previous 3 to 90 days to 1g daily of fish oil (n=289) or placebo (n=297). Patients were recruited from January 2008 to March 2011 and followed for 12 months or time to death or recurrent AF. The primary end point was the time to first recurrence of symptomatic or asymptomatic AF documented by 12-lead ECG.

Results. At 12 months, 18.9% of patients on placebo had a recurrence of AF compared with 24.0% of those who took fish oil (HR=1.28, P=.17). There was no difference between treatment with fish oil and placebo for any other prespecified end points.

Conclusions. Pharmacologic supplementation with 1g of PUFA does not reduce AF recurrence in patients with previous AF who have recovered normal sinus rhythm.

Fish Oil for the Prevention of Post-Operative Atrial Fibrillation: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Trial19Presenter: Roberto Marchioli, Santa Maria Imbaro, Italy.

Background. Postoperative AF or flutter is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-PUFA reduce postoperative AF, with mixed results. The aim was to determine whether perioperative n-3-PUFA supplementation reduces postoperative AF.

Methods. The Omega-3 Fatty Acids for Prevention of Post- operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment. Patients were randomized to receive fish oil (1-g capsules containing ≥840mg n-3-PUFA as ethyl esters) or placebo, with preoperative loading of 10g over 3 to 5 days (or 8g over 2 days) followed postoperatively by 2g/d until hospital discharge or postoperative day 10, whichever came first. The main outcome measure was the occurrence of postoperative AF lasting longer than 30seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in sym ptoms, or treate d with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse CV events, 30-day mortality, bleeding, and other adverse events.

Results. At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, [OR]=0.96; 95% CI, 0.77-1.20; P=.74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%]; P=.70) or number of postoperative AF episodes per patient (1 episode, 156 [20.6%] vs 157 [20.7%]; 2 episodes, 59 [7.8%] vs 49 [6.5%]; ≥3 episodes, 18 [2.4%] vs 21 [2.8%]); (P=.73). Supplementation with n-3-PUFA was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events.

Conclusion. In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFA, compare d with placebo, did not re duce the risk of postoperative AF.

A Randomized Trial of a Multivitamin in the Prevention of Cardiovascular Disease in Men: The Physicians’ Health Study II20Presenter: Howard D. Sesso, Boston, Massachusetts, United States.

Background. Although multivitamins are used to prevent vitamin and mineral deficiency, there is a perception that multivitamins may prevent cardiovascular disease (CVD). Observational studies have shown inconsistent associations between regular multivitamin use and CVD, with no long-term clinical trials of multivitamin use. The objective was to determine whether long-term multivitamin supplementation decreases the risk of major cardiovascular events among men.

Methods. The Physicians’ Health Study II, a randomized, double- blind, placebo-controlled trial of a common daily multivitamin, began in 1997 with continued treatment and follow-up through June 1, 2011. A total of 14 641 male US physicians initially aged 50 years or older (mean, 64.3 [SD, 9.2] years), including 754 men with a history of CVD at randomization, were enrolled. Patients were randomized to daily multivitamin or placebo. The main outcome measures were the composite end point of major cardiovascular events, including nonfatal MI, nonfatal stroke, and CVD mortality. Secondary outcomes included MI and stroke individually.

Results. During a median follow-up of 11.2 [interquartile range, 10.7-13.3] years, there were 1732 confirmed major cardiovascular events. Compared with placebo, there was no significant effect of a daily multivitamin on major cardiovascular events (11 and 10.8 events per 1000 person-years for multivitamin vs placebo, respectively; HR=1.01; 95%CI, 0.91-1.10; P=.91). Further, a daily multivitamin had no effect on total MI (3.9 and 4.2 events per 1000 person-years; HR=0.93; 95% CI, 0.80-1.09; P=.39), total stroke (4.1 and 3.9 events per 1000 person-years; HR= 1.06; 95% CI, 0.91-1.23; P=.48), or CVD mortality (5.0 and 5.1 events per 1000 person-years; HR=0.95; 95% CI, 0.83-1.09; P=.47). A daily multivitamin was also not significantly associated with total mortality (HR=0.94; 95% CI, 0.88-1.02; P=.13). The effect of a daily multivitamin on major cardiovascular events did not differ between men with or without a baseline history of CVD (P=.62 for interaction).

Conclusions. Among this population of US male physicians, taking a daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up.

Use of a Multidrug Pill In Reducing Cardiovascular Events (UMPIRE)21Presenter: Simon A. Thom, London, United Kingdom.

Background. Preventive therapies that address multiple CV risk factors are limited. Novel approaches are needed. A CVD preventive strategy consisting of a combination of aspirin, a statin, and 2 BP-lowering agents is one option that may reduce CV events. The objective of the study was to test the polypill compared to usual medications in patients with established CVD and those who are at high risk to increase adherence to guideline-indicated therapy and improve BP and LDL-cholesterol (LDL-C) in people at high risk.

Methods. This study randomized 2004 subjects from India and Europe to a polypill strategy, fixed-dose combination (FDC) or usual care (UC). Two versions were applied: a) aspirin 75mg, simvastatin 40mg, lisinopril 10mg and atenolol 50mg, or b) hydrochlorothiazide 12.5mg instead of atenolol. The primary outcome was adherence to indicated medications, based on self-report.

Results. Adherence was 86% on FDC, 65% on UC with 1.22 treatment effect (95% CI, 1.24-1.41).

Conclusions. Improvement in adherence occurs with FDC, including antiplatelet, statin and BP-lowering drugs. Both BP and cholesterol also improved in patients with CVD and a 33% increase in adherence in 15 months was reported.

Novel Treatments for Managing Lipids DisordersReduction of Low-density Lipoprotein Cholesterol With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD): Interim Results From a Phase 2, Randomized, Double-blind, Placebo-controlled Trial22Presenter: Frederick Raal, Johannesburg, South Africa.

Background. Despite statin treatment, many patients with heterozygous familial hypercholesterolemia do not reach desired low- density lipoprotein cholesterol (LDL-C) targets. AMG145, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease, demonstrated significant reductions in LDL-C in phase 1 studies. This phase 2, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluated the ef f icacy and saf e ty of AMG145 in he t e r ozy g ous f amilial hypercholesterolemia patients.

Methods. Patients with heterozygous familial hypercholesterolemia diagnose d by Simon Broome criteria with LDL-C ≥2.6 mmol/L (100mg/dL) despite statin therapy with or without ezetimibe were randomized 1:1:1 to AMG145 350mg, AMG145 420mg, or placebo- administered subcutaneously every 4 weeks. The primary end point was percentage change from baseline in LDL-C at week 12.

Results. Of 168 patients randomized, 167 received investigational product and were included in the full analysis set, with mean [SD] age, 50 [13] years; 47% female; 89% white; mean [SD] baseline LDL-C, 4.0 [1.1] mmol/L (156 [42] mg/dL). At week 12, LDL-C reduction measured by preparative ultracentrifugation (least squares mean [standard error (SE)]) was 43 (3)% and 55 (3)% with AMG145 350mg and 420mg, respectively, compared with 1 (3)% increase with placebo (P<.001 for both dose groups). Serious adverse events (not considered treatment-related) occurred in 2 patients on AMG145.

Conclusions. AMG145 administered every 4 weeks yielded rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use, with or without ezetimibe, with minimal adverse events and g ood tolerability.

Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects (GAUSS): Interim Results From a Randomized, Double-blind, Placebo-controlled Study23Presenter: Evan Stein, Cincinnati, Ohio, United States.

Background. An estimated 10% to 20% of patients cannot tolerate statins or adequate doses to achieve treatment goals. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low- density lipoprotein (LDL) receptors, promoting their degradation and increasing LDL cholesterol levels. In phase 1 studies, a human monoclonal antibody to PCSK9, AMG145, was well tolerated and reduced LDL cholesterol levels. The objective of the study was to assess the efficacy and tolerability of AMG145 in patients with statin intolerance due to muscle-related side effects.

Methods. This is a 12-week, randomized, double-blind, placebo- and ezetimibe-controlled, dose-ranging study conducted between July 2011 and May 2012 in statin-intolerant adult patients at 33 international sites. Patients were randomized equally to 1 of 5 groups: AMG145 alone at doses of 280mg, 350mg, or 420mg; AMG145 at 420mg plus 10mg of ezetimibe; or 10mg of ezetimibe plus placebo. AMG145 or placebo was administered subcutaneously every 4 weeks. The primary end point was percentage change from baseline to week 12 in ultracentrifugation-measured LDL cholesterol. Other end points included measures of safety and tolerability of different doses of AMG145 and AMG145 plus ezetimibe.

Results. Of 236 patients screened, 160 were randomized (mean age, 62 years; 64% female; mean baseline LDL cholesterol, 193mg/dL); all patients had intolerance to 1 or more statins because of muscle- related events. At week 12, mean changes in LDL cholesterol levels were −67mg/dL (−41%; 95% CI, −49% to −33%) for the AMG145, 280-mg, group; −70mg/dL (−43%; 95% CI, −51% to −35%) for the 350-mg group; −91mg/dL (−51%; 95% CI, −59% to −43%) for the 420-mg group; and −110mg/dL (−63%; 95% CI, −71% to −55%) for the 420-mg/ezetimibe group compared with −14mg/dL (−15%; 95% CI, −23% to −7.0%) for the placebo/ezetimibe group (P<.001). Four serious adverse events were reported with AMG145 (CAD, acute pancreatitis, hip fracture, syncope). Myalgia was the most common treatment- emergent adverse event during the study, occurring in 5 patients (15.6%) in the 280-mg group (n=32); 1 patient (3.2%) in the 350-mg group (n=31), 1 patient (3.1%) in the 420-mg group (n=32), 6 patients (20%) receiving 420-mg AMG145/ezetimibe, and 1 patient (3.1%) receiving placebo/ezetimibe.

Conclusions. In this phase 2 study in statin-intolerant patients, subcutaneous administration of a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels and was associated with short-term tolerability.

Effects of 12 Weeks of Treatment With RN316 (PF-04950615), a Humanized IgG2Δa Monoclonal Antibody Binding Proprotein Convertase Subtilisin Kexin Type 9, in Hypercholesterolemic Subjects on High and Maximal Dose Statins24Presenter: Barry Gumbiner, San Diego, California, United States.

Background. Proprotein convertase subtilisin kexin type 9 (PCSK9) binds to LDL-C receptors preventing LDL-C clearance, therefore increasing LDL-C levels in the blood. RN316, a humanized monoclonal antibody, binds to PCK9 preventing down-regulation of the LDL-C receptors, which has been shown to improve LDL-C clearance, and therefore reducing LDL-C levels. The objective of the study was to evaluate effects of RN316 on LDL-C levels in patients on high-to- maximal doses of atorvastatin, rosuvastatin, or simvastatin.

Methods. In this Phase 2, double-blind, randomized, placebo- controlled study, 135 patients already undergoing statin treatment were randomized to 1 of 5 treatment arms: placebo, 0.25mg/kg, 1.0mg/kg, 3.0mg/kg, or 6.0mg/kg of RN316 administered every 4 weeks for 12 weeks with an 8-week follow-up period.

Results. LDL-C levels were significantly decreased with 3mg/kg and 6mg/kg dose of RN316 in addition to high- or maximal-dosage statin treatment. Total cholesterol was also reduced and levels of HDL-C increased. No significant changes were observed in triglycerides across any of the 5 treatment arms. Very few drug-related adverse events were observed. Those that did occur were mild and resolved with no intervention. The effect on LDL-C persisted for 4 weeks posttreatment.

Conclusions. RN316 significantly lowered LDL-C in addition to high or maximal statin dosage and was generally safe and well tolerated.

Effects of the Cholesteryl Ester Transfer Protein Inhibitor Dalcetrapib in Patients With Recent Acute Coronary Syndrome25Presenter: Gregory G. Schwartz, Denver, Colorado, United States.

Background. In observational analyses, higher levels of high- density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces CV risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve CV outcomes.

Methods. We randomly assigned 15 871 patients who had a recent ACS to receive the CETP inhibitor dalcetrapib at a dose of 600mg daily or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal MI, ischemic stroke, unstable angina, or cardiac arrest with resuscitation.

Results. At the time of randomization, the mean HDL cholesterol level was 42mg per deciliter (1.1 mmol per liter), and the mean low- density lipoprotein (LDL) cholesterol level was 76mg per deciliter (2 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4% to 11% in the placebo group and by 31% to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; HR with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2mg/L higher and the mean systolic BP was 0.6mm Hg higher with dalcetrapib, compared with placebo (P<.001 for both comparisons).

Conclusions. In patients with a recent ACS, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent CV events.

Cell-based Therapies for Myocardial Regeneration26Results of the Swiss Multicenter Intracoronary Stem Cells Study in Acute Myocardial Infarction (Swiss AMI) TrialPresenter: Daniel Sürder, Lugano, Switzerland.

Bac kgr ound. R ecent s tudies r eport that intr acor onar y administration of autologous bone marrow mononucleated cells (BM-MNCs) may improve remodeling of the left ventricle after acute myocardial infarction (AMI). Subgroup analysis suggests that early treatment between days 4 and 7 after AMI is probably most effective; however, the optimal time point of intracoronary cell administration has never been addressed in clinical trials. Furthermore, reliable clinical predictors are lacking for the identification of patients who are thought to benefit most from cellular therapy.

Methods. In a multicenter trial, 200 patients with AMI successfully treated by PCI of the infarct-related artery were randomized in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group was treated with state-of-the-art medical management. The treatment groups received intracoronary administration of autologous BM-MNC at 5 to 7 days or 3 to 4 week s after the initial event, respectively. Left ventricular function as well as scar size, transmural extension, and regional wall motion score were assessed by cardiac magnetic resonance (CMR) studies at baseline and after 4 and 12 months. The primary end point was the change in global left ventricular (LV) ejection fraction by CMR at 4 months as compared to baseline. Secondary end points included change in LV volumes, infarct size (DE CMR) and regional myocardial thickening. MACE (death, MI, coronary revascularization, stroke) and predictors for efficacy (time to reperfusion, transmurality, microvascular obstruction) were assessed.

Results. Intracoronary infusion of BM-MNC, either 5-7 d or 3-4 weeks after primary PCI for STEMI, did not improve LV function as assessed by CMR at 4 months compared with control. Subgroup analysis indicates potential benefit of intracoronary BM-MNC in patients with early reperfusion (within 4.5h from the onset of pain)

Conclusions. Intracoronary infusion of BM-MNC did not improve left ventricular function as assessed by MRI compared with controls either at 1 week or 4 weeks after primary PCI for ST-elevation MI. However, subgroup analysis suggests this approach may offer some benefit in patients reperfused within 4.5hours of the onset of chest pain.

The Effect of Timing of Stem Cell Delivery Following Acute Myocardial Infarction: The NHLBI and CCTRN TIME Trial27Presenter: Jay H. Traverse, Minneapolis, Minnesota, United States.

Background. While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed. The objective of the study was to determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect.

Methods. A randomized, 2 × 2 factorial, double-blinded, placebo- controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤45%) after successful primary PCI of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute. The intervention consisted of intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI. The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 versus day 7. The secondary end points included major adverse CV events as well as changes in left ventricular volumes and infarct size.

Results. The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants we re male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) versus the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P=.96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no signif icant dif ferences in change in global left ventricular function for patients treated at day 3 (−0.9% [95% CI,−6.6% to 4.9%], P=.76) or day 7 (1.1% [95%CI, −4.7% to 6.9%], P=.70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups.

Conclusions. Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo.

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy28Presenter: Joshua M. Hare, Miami, Florida, United States.

Background. Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. The objective was to test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.

Methods. A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. Main outcome measures were 30-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments include d 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index.

Results. Within 30 days, 1 patient in each group (treatment- emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n=5) in the allogeneic group and 53.3% (n=8) in the autologous group (P=.46). At 1 year, no ventricular arrhythmia SAEs were observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P=.10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P<.001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate signif icant donor-specific alloimmune reactions.

Conclusions. In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment- emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling.

Effect of Cardiac Stem Cells In Patients With Ischemic Cardiomyopathy: Interim Results of the SCIPIO Trial Up to 2 Years After Therapy29Presenter: Roberto Bolli, Louisville, Kentucky, United States.

Background. The aim was to evaluate the usefulness of cardiac stem-cell (CSC), instead of cells derived from bone marrow, in heart- failure patients.

Methods. This is a phase 1, randomized, open-label trial of c-KIT- positive CSCs in patients with left ventricular dysfunction (LVEF <40%) following an MI. In the trial, the cells were harvested from the patient's right atrial appendage, isolated and expanded, and then infused to repair an infarction during coronary bypass surgery.

Results. Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 29.0% before infusion to 36.0% (P<.001) 4 months after the procedure. During that period, LVEF improved only from 29.2% to 29.4% in 13 control patients. The benefits seen in the treated group grew relative to the control group at 1-year and 2-year follow-up. The average LVEF grew insignificantly from 30.3% at baseline to 31.7% at 1 year post-procedure in the 12 control patients followed that long. In 17 patients in the CSC-treatment group at 1-year follow-up, LVEF increased to 37.8% from a baseline average of 29.7%. At 2 years, 5 control patients still showed no significant change in LVEF, while average LVEF rose to 41.7% in the 12 CSC-treated patients who had reached the 2-year follow-up. Global wall-motion scores declined slightly in the control group over 24 months but improved from –2.50 to –3.92 (P=.006) in the treatment group. Cardiac MRI showed that the CSC-treated patients had statistically significant improvements in mass of nonviable myocardial tissue and the percentages of viable tissue within the infarcted region. Minnesota Heart Failure Scores improved significantly in the CSC-treated patients while remaining almost flat in the control group. No adverse effects attributable to CSCs have been reported in the trial out to 2 years.

Conclusions. CSC is a useful treatment in patients with left ventricular dysfunction. Further studies are required to evaluate its potential.

Management of Left Ventricle Dysfunction: Devices and DrugsMADIT Randomized Trial to Reduce Inappropriate Therapy (MADIT-RIT)30Presenter: Arthur J. Moss, Rochester, New York, United States.

Background. The implantable cardioverter–defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential adverse effects.

Methods. We randomly assigned 1500 patients with a primary- prevention indication to receive an ICD with 1 of 3 programming configurations. The primary objective was to determine whether programmed high-rate therapy (with a 2.5-second delay before the initiation of therapy at a heart rate of ≥20 0 beats per minute) or delayed therapy (with a 60-second delay at 170 to 199 beats per minute, a 12-second delay at 20 0 to 249 beats per minute, and a 2.5-second delay at ≥250 beats per minute) was associated with a decrease in the numb er of patients with a first occurrence of inappropriate antitachycardia pacing or shocks, as compared with conventional programming (with a 2.5-second delay at 170 to 199 beats per minute and a 1.0-second delay at ≥200 beats per minute).

Results. During an average follow-up of 1.4 years, high-rate therapy and delayed ICD therapy, as compared with conventional device programming, were associated with reductions in a first occurrence of inappropriate therapy (HR with high-rate therapy vs conventional therapy, 0.21; 95% CI, 0.13 to 0.34; P<.0 01; HR with delayed therapy vs conventional therapy, 0.24; 95% CI, 0.15 to 0.40; P<.0 01) and reductions in all-cause mortality (HR with high-rate therapy vs conventional therapy, 0.45; 95% CI, 0.24 to 0.85; P=.01; HR with delayed therapy vs conventional therapy, 0.56; 95% CI, 0.30 to 1.02; P=.06). There were no significant differences in procedure- related adverse events among the 3 treatment groups.

Conclusions. Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher, as compared with conventional programming, was associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up.

Biventricular Versus Right Ventricular Pacing in Patients With Left Ventricular Dysfunction and Atrioventricular Block (BLOCK HF Study)31Presenter: Anne B. Curtis, Buffalo, New York, United States.

Background. The objective of the study was to evaluate if biventricular (BiV) pacing can prevent progression of heart failure and its clinical and economic consequences in patients with AV block.

Methods. Eligibility criteria were a) AV block necessitating pacing; b) LVEF <50%; c) NYHA class I, II or III; d) absence of a class I indication for CRT; and e) no previous pacemaker or ICD. Echocardiography was performed at randomization, 6, 12, 18 and 24 months. The primary end point was the composite of all-cause mortality, heart failure- related urgent care or increase in LV end-systolic volume.

Results. A total of 691 patients were randomized; 349 were allocated to BiV pacing and 342 to RV pacing. Average follow-up was more than 36 months in both groups. The primary endpoint was reached more frequently in the RV pacing group (HR=0.74; 95%CI, 0.6-0.8).

Conclusions. In patients with AV block and LV systolic dysfunction, BiV pacing compared to RV pacing leads to a significant 26% reduction in the combined end point of mortality, heart failure related urgent care and increase in LV end systolic volume.

Pilot Trial of Two Levels of Hypothermia in Comatose Survivors From Out-of-hospital Cardiac Arrest32Presenter: Esteban Lopez-de-Sa, Madrid, Spain.

Background. It is recommended that comatose survivors of out- of-hospital cardiac arrest should be cooled to 32° to 34°C for 12 to 24hours. However, the optimal level of cooling is unknown. The aim of this pilot study was to obtain initial data on the effect of different levels of hypothermia. We hypothesized that deeper temperatures will be associated with better survival and neurological outcome.

Methods. Patients were eligible if they had a witnessed out-of- hospital cardiac arrest from March 20 08 to August 2011. Target temperature was randomly assigned to 32°C or 34°C. Enrollment was stratified on the basis of the initial rhythm as shockable or asystole. The target temperature was maintained during 24hours followed by 12 to 24hours of controlled rewarming. The primary outcome was survival free from severe dependence (Barthel Index score ≥60 points) at 6 months.

Results. Thirty-six patients were enrolled in the trial (26 shockable rhythm, 10 asystole), with 18 assigned to 34°C and 18 to 32°C. Eight of 18 patients in the 32°C group (44.4%) met the primary end point compared with 2 of 18 in the 34°C group (11.1%) (log-rank P=.12). All patients whose initial rhythm was asystole died before 6 months in both groups. Eight of 13 patients with initial shockable rhythm assigned to 32°C (61.5%) were alive free from severe dependence at 6 months compared with 2 of 13 (15.4%) assigned to 34°C (log-rank P=.029). The incidence of complications was similar in both groups except for the incidence of clinical seizures, which was lower (1 versus 11; P=.0002) in patients assigned to 32°C compared with 34°C. On the contrary, there was a trend toward a higher incidence of bradycardia (7 versus 2; P=.054) in patients assigned to 32°C. Although potassium levels decreased to a greater extent in patients assigned to 32°C, the incidence of hypokalemia was similar in both groups.

Conclusions. The findings of this pilot trial suggest that a lower cooling level may be associated with a better outcome in patients surviving out-of-hospital cardiac arrest secondary to a shockable rhythm. The benefits observed here merit further investigation in a larger trial in out-of-hospital cardiac arrest patients with different presenting rhythms.

The Relaxin in Acute Heart Failure (RELAX-AHF-1) Trial33Presenter: John R. Teerlink, San Francisco, California, United States.

Background. Serelaxin, recombinant human relaxin-2, is a vasoactive peptide hormone with many biological and haemodynamic effects. In a pilot study, serelaxin was safe and well tolerated with positive clinical outcome signals in patients with acute heart failure. The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo.

Methods. RELAX-AHF was an international, double-blind, placebo- controlled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned (1:1) via a central randomisation scheme blocked by study centre to standard care plus 48-h intravenous infusions of placebo or serelaxin (30μg/kg per day) within 16h from presentation. All patients had dyspnoea, congestion on chest radiograph, increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic BP greater than 125mm Hg. Patients, personnel administering study drug, and those undertaking study-related assessments were masked to treatment assignment. The primary endpoints evaluating dyspnoea improvement were change from baseline in the visual analogue scale area under the curve (VAS AUC) to day 5 and the pr oportion of patients with moderat e or mar k e d dy spnoea improvement measured by Likert scale during the first 24h, both analysed by intention to treat.

Results. 1161 patients were randomly assigned to serelaxin (n=581) or placebo (n=580). Serelaxin improved the VAS AUC primary dyspnoea endpoint (448mm × h, 95% CI 120—775; P=.007) compared with placebo, but had no significant effect on the other primary endpoint (Likert scale; placebo, 150 patients [26%]; serelaxin, 156 [27%]; P=.70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo, 75 events [60-day Kaplan-Meier estimate, 13.0%]; serelaxin, 76 events [13.2%]; Hazard ratio [HR]=1.02 [95% CI, 0.74-1.41], P=.89] or days alive out of the hospital up to day 60 (placebo, 47.7 [12.1] days; serelaxin, 48.3 [11.6]; P=0.37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42; HR=0.63; 95% CI, 0.42-0.93; P=.019).

Conclusions. Treatment of acute heart failure with serelaxin was associated with dyspnoea relief and improvement in other clinical outcomes, but had no effect on readmission to hospital. Serelaxin treatment was well tolerated and safe, supported by the reduced 180- day mortality.

Cardiorenal Rescue Study in Acute Decompensated Heart Failure: Results of CARRESS-HF, for the Heart Failure Clinical Research Network34Presenter: Bradley A. Bart, Minneapolis, Minnesota, United States.

Background. Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the ef f icacy and safety of ultrafiltration in patients with acute decompensated heart failure complicated by persistent congestion and worsened renal function.

Methods. We randomly assigned a total of 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion to a strategy of stepped pharmacologic therapy (94 patients) or ultrafiltration (94 patients). The primary end point was the bivariate change from baseline in the serum creatinine level and body weight, as assessed 96hours after random assignment. Patients were followed for 60 days.

Results. Ultrafiltration was inferior to pharmacologic therapy with respect to the bivariate end point of the change in the serum creatinine level and body weight 96hours after enrollment (P=.003), owing primarily to an increase in the creatinine level in the ultrafiltration group. At 96hours, the mean change in the creatinine level was−0.04±0.53mg/dL (−3.5±46.9μmol/L) in the pharmacologic-therapy group, as compared with +0.23±0.70mg/dL (20.3±61.9μmol/L) in the ultrafiltration group (P=.003). There was no significant difference in weight loss 96hours after enrollment between patients in the pharmacologic-therapy group and those in the ultrafiltration group (a loss of 5.5±5.1kg [12.1±11.3 lb] and 5.7±3.9kg [12.6±8.5 lb], respective ly; P =.58). A higher percentage of patients in the ultrafiltration group than in the pharmacologic-therapy group had a serious adverse event (72% vs 57%, P=.03).

Conclusions. In a randomized trial involving patients hospitalized for acute decompensated heart failure, worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultraf iltration for the preservation of renal function at 96hours, with a similar amount of weight loss with the 2 approaches. Ultrafiltration was associated with a higher rate of adverse events.

References
[1]
L. Pérez de Isla, A. Bayes-Genis, J. Sanchis, M. Heras.
Resumen de los ensayos clínicos presentados en las Sesiones Científicas Anuales del American College of Cardiology (Atlanta Estados Unidos, 14-16 de marzo de 2010).
Rev Esp Cardiol, 63 (2010), pp. 695-707
[2]
A. Bayes-Genis, P. Avanzas, L. Pérez de Isla, J. Sanchis, M. Heras.
Resumen de estudios clínicos presentados en el Congreso de 2010 de la European Society of Cardiology (28 de agosto-1 de septiembre de 2010, Estocolmo Suecia).
Rev Esp Cardiol, 63 (2010), pp. 1292-1303
[3]
P. Avanzas, A. Bayes-Genis, L. Pérez de Isla, J. Sanchis, M. Heras.
Resumen de los ensayos clínicos presentados en las Sesiones Científicas Anuales de la American Heart Association (Chicago Estados Unidos, 13-17 de noviembre de 2010).
Rev Esp Cardiol, 64 (2011), pp. e1-e8
[4]
P. Avanzas, L. Pérez de Isla, A. Bayes-Genis, J. Sanchis, M. Heras.
Resumen de los ensayos clínicos presentados en las Sesiones Científicas Anuales del American College of Cardiology (Nueva Orleans, Luisiana Estados Unidos, 2-5 de abril de 2011).
Rev Esp Cardiol, 64 (2011), pp. e1-e8
[5]
P. Avanzas, A. Bayes-Genis, L. Pérez de Isla, J. Sanchis, M. Heras.
Resumen de estudios clínicos presentados en el Congreso de 2011 de la European Society of Cardiology (27-30 de agosto de 2011, París Francia).
Rev Esp Cardiol, 64 (2011), pp. e1-e8
[6]
P. Avanzas, A. Bayes-Genis, L. Pérez de Isla, J. Sanchis, M. Heras.
Resumen de los ensayos clínicos presentados en las Sesiones Científicas Anuales de la American Heart Association (Orlando Estados Unidos, 12-16 de noviembre de 2011).
Rev Esp Cardiol, 65 (2012), pp. e1-e9
[7]
P. Avanzas, A. Bayes-Genis, L. Pérez de Isla, J. Sanchis, M. Heras.
Resumen de los ensayos clínicos presentados en las Sesiones Científicas Anuales del American College of Cardiology (Chicago, Illinois Estados Unidos, 24-27 de marzo de 2012).
Rev Esp Cardiol, 65 (2012), pp. e1-e8
[8]
P. Avanzas, A. Bayes-Genis, L. Pérez de Isla, J. Sanchis, M. Heras.
Resumen de estudios clínicos presentados en el Congreso de 2012 de la Sociedad Europea de Cardiología (25-29 de agosto de 2012, Múnich Alemania).
Rev Esp Cardiol, 65 (2012), pp. e1-e8
[9]
Brighton, T.A., Eikelboom, J.W., Mann, K., Mister, R., Gallus, A., Ockelford, P., et, al., Low-dose aspirin for preventing recurrent venous, thromboembolism., New Engl, J., Med., 2012, Nov 4. DOI: 10.1056/NEJMoa1210384 [Accessed 17 Nov 2012]. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1210384?query=featured_home.
[10]
Collet JP, Cuisset T, Rangé G, Cayla G, Elhadad S, Pouillot C, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. New Engl J Med. 2012, Nov 4. DOI: 10.1056/NEJMoa1209979 [Accessed 17 Nov 2012]. Available at: http://www. nejm.org/doi/full/10.1056/NEJMoa1209979?query=featured_home.
[11]
Gurbel PA, Erlinge D, Ohman EM, Neely B, Neely M, Goodman SG, et al. Platelet function during extended prasugrel and clopidogrel therapy for patients with ACS treated without revascularization. The TRILOGY ACS Platelet Function Substudy. JAMA. 2012; Nov 7 [Accessed 17 Nov 2012]. Available at: http://jama.jamanetwork. com/article.aspx?articleid=1389509.
[12]
Results of the Trial to Assess Chelation Therapy [Accessed 17 Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/Scientif icSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_Article.jsp.
[13]
Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, et al. Strategies for multivessel revascularization in patients with diabetes. New Engl J Med. 2012, Nov 4. DOI: 10.1056/NEJMoa1211585 [Accessed 17 Nov 2012]. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1211585?query=featured_home.
[14]
Health economics and quality of life in contemporary trials. Prospective evaluation of outcomes with stress perfusion imaging versus stress wall motion imaging during dobutamine or exercise echocardiography [Accessed 17 Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/Scientif icSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_Article.jsp.
[15]
Economic outcomes of percutaneous coronary intervention performed at sites with and without on-site cardiac surgery [Accessed 17 Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/ScientificSessions/ScienceNews/SS11- Late-Breaking-Clinical-Trials_UCM_432888_Article.jsp.
[16]
Quality of Life Outcomes in the Trial to Assess Chelation Therapy (TACT) [Accessed. Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/ScientificSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_ Article.jsp.
[17]
Cost-effectiveness of PCI with drug eluting stents versus bypass surgery for patients with diabetes and multi-vessel coronary artery disease: Results from the FREEDOM trial [Accesse d 17 Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/ScientificSessions/ScienceNews/SS11-Late-Breaking-Clinical- Trials_UCM_432888_Article.jsp.
[18]
Treatments for prevention of cardiovascular events: a population perspective. Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: Results of a double-blind randomized clinical trial (FORWARD) [Accessed 17 Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/ScientificSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_ Article.jsp.
[19]
Mozaffarian, Marchioli R, Macchia A, Silletta MG, Ferrazzi P, Gardner TJ, et al. Fish oil and postoperative atrial fibrillation. The Omega-3 Fatty Acids for Prevention of P o s t-oper ati v e A trial F ibrillation (OPERA) r andomize d trial. JAMA. 2012;208:2001-11. doi:10.1001/jama.2012.28733 [Accessed 17 Nov 2012]. Available at: http://jama.jamanetwork.com/article.aspx?articleid=1389226.
[20]
Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, et al. Multivitamins in the prevention of cardiovascular disease in men. The Physicians’ Health Study II randomized controlled trial. JAMA. 2012;308:1751-60. doi:10.1001/jama.2012.14805 [Accessed 17 Nov 2012]. Available at: http://jama.jamanetwork. com/article.aspx?articleid=1389615.
[21]
Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE) [Accessed 17 Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/ScientificSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_ Article.jsp.
[22]
Raal F, Scott R, Somaratne R, Bridges I, Li G, Wasserman SM, et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: The Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012, Nov 5. doi: 10.1161/?CIRCULATIONAHA.112.144 055 [Accessed 17 Nov 2012]. Available at: http://circ.ahajournals.org/content/early/2012/11/02/CIRCULATIONAHA.112.144055.full.pdf+html.
[23]
Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V, et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients. The GAUSS randomized trial. JAMA. 2012 Nov 5;308:1-10. DOI: 10.1001/jama.2012.25790 [Accessed 17 Nov 2012]. Available at: http://jama.jamanetwork. com/article.aspx?articleid=1389227.
[24]
Effects of 12 weeks of treatment with RN316 (PF-04950615), a humanized IgG2Δa monoclonal antibody binding proprotein convertase subtilisin kexin type 9, in hypercholesterolemic subjects on high and maximal dose statins [Accessed 17 Nov 2012]. Available at: http://my.americanheart.or g/prof essional/Sessions/ScientificSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_ Article.jsp.
[25]
Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. New Engl J Med. 2012, Nov 5. DOI: 10.1056/NEJMoa1206797 [Accessed 17 Nov 2012]. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1206797?query=featured_home.
[26]
Cell-based therapies for myocardial regeneration [Accessed 17 Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/ScientificSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_Article.jsp.
[27]
Traverse JH, Henry TD, Pepine CJ, Willerson JT, Zhao DXM, Ellis SG, et al. Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction. The TIME randomized trial. JAMA. 2012 Nov 6;308:1-10. doi:10.1001/jama.2012.28726 [Accessed 17 Nov 2012]. Available at: http://jama.jamanetwork.com/article.aspx?articleid=1388971.
[28]
Hare JH, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, et al. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy. The POSEIDON Randomized Trial. JAMA. 2012 Nov 6;308:1-11. doi:10.1001/jama.2012.25321 [Accessed 17 Nov 2012]. Available at: http://jama. jamanetwork.com/article.aspx?articleid=1388970.
[29]
Effect of cardiac stem cells in patients with ischemic cardiomyopathy: interim results of the SCIPIO trial up to 2 years after therapy [Accessed 17 Nov 2012]. Available at: http://my.americanheart.org/professional/Sessions/ScientificSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_Article.jsp.
[30]
Moss AJ, Schuger C, Beck CA, Brown MW, Cannom DS, Daubert JP, et al. Reduction in inappropriate therapy and mortality through ICD programming. New Engl J Med. 2012 Nov 6. DOI: 10.1056/NEJMoa1211107 [Accessed 17 Nov 2012]. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1211107.
[31]
Biventricular versus Right Ventricular Pacing in Patients with Left Ventricular Dysfunction and Atrioventricular Block (BLOCK HF Study) [Accessed 17 Nov 2012]. A v ailable at: http://m y .americanheart.or g/pr of essional/Sessions/ScientificSessions/ScienceNews/SS11-Late-Breaking-Clinical-Trials_UCM_432888_ Article.jsp.
[32]
Lopez-de-Sa E, Rey JR, Armada E, Salinas P, Viana-Tejedor A, Espinosa-Garcia S, et al. Hypothermia in comatose survivors from out-of-hospital cardiac arrest. Pilot trial comparing 2 levels of target temperature. Circulation. 2012 Nov 6. DOI: 10.1161/?CI RCULATIONAHA.112.136408 [Accessed 17 Nov 2012]. Available at: http://circ. ahajournals.org/content/early/2012/11/06/CIRCULATIONAHA.112.136408.abstract? sid=1dbab713-10c9-4064-9502-afdba4033448.
[33]
Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet. 2012 Nov 7. DOI:10.1016/S0140-6736(12)61855-8 [Accessed 17 Nov 2012]. Available at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61855-8/fulltext# article_upsell.
[34]
Bart BA, Goldsmith SR, Lee KL, Givertz MM, O’Connor CM, Bull DA, et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. New Engl J Med. 2012, Nov 6. DOI: 10.1056/NEJMoa1210357 [Accessed 17 Nov 2012]. Av ailable at: http://www.nejm.or g/doi/full/10.1056/NEJMoa12103 57? query=featured_home.
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