The RECALCAR registry1 has demonstrated a high prevalence of classic cardiovascular risk factors in Spain, which is disproportionate with the low incidence of cardiovascular diseases compared with other European countries. A possible explanation for this contrast is that the negative impact on health of some of these risk factors, such as the increasing rates of obesity and diabetes as well as smoking in women, still has not had sufficient time to increase the incidence of cardiovascular diseases.

In the EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) IV study,32 most patients did not meet the established therapeutic objectives for their risk factors, even though a high percentage of patients with CAD received proper treatment. According to a recent meta-analysis, approximately 9% of cardiovascular events in Europe could be attributed to a low degree of adherence to treatment with statins and antihypertensive medications as there is an inverse association between the degree of adherence and the risk of events.33

The latest data from clinical drug trials have focused on antidiabetic and hypolipidemic agents. Two dipeptidyl peptidase-4 inhibitors, saxagliptin and alogliptin, were tested in the SAVOR-TIMI 5334,35 and EXAMINE36 studies, respectively. Both inhibitors were not inferior to placebo for the appearance of adverse cardiovascular events. Saxagliptin, however, was associated with an increase in hospitalizations due to heart failure (HR = 1.27; 95%CI, 1.07-1.51), especially in patients with elevated levels of natriuretic peptides, a history of heart failure, or chronic kidney failure. Therefore, its use is not recommended in patients with cardiovascular disease.35

Although low high-density lipoprotein cholesterol levels are a powerful independent predictor for cardiovascular risk, recent data suggest that this may not be applicable to high-risk patients treated with statins. When low high-density lipoprotein cholesterol levels were evaluated in patients treated with different statin doses low high-density lipoprotein cholesterol levels were only related to increased cardiovascular risk in those not taking statins or only taking low statin doses, but not in those taking high doses.37 In a recent meta-analysis, high-density lipoprotein cholesterol-targeted drug treatments with niacin, fibrates, and cholesteryl ester transfer protein inhibitors (combined with statins) did not reduce the number of cardiovascular events.38

An important innovation is the publication of the results obtained with PCSK9 inhibitors. These drugs had already been shown to be effective at significantly reducing low-density lipoprotein cholesterol in phase II studies. The reduction was maintained with a 1-year treatment, showing good tolerance to the drug, in the recent OSLER study.39 The results of the LAPLACE-2 study40 have also shown that the combination of evolucumab and a statin significantly reduced low-density lipoprotein cholesterol when compared with a statin plus ezetimibe or a statin alone.

The GAUSS-241 and MENDEL-242 studies evaluated the efficacy of evolucumab in hypercholesterolemic patients with intolerance to statins. In both studies, significant reductions were obtained in low-density lipoprotein cholesterol compared to ezetimibe and placebo, with no increase in adverse effects. Despite promising results, PCSK9 inhibitors will have to demonstrate their superiority over statins in the prevention of cardiovascular events. Lastly, we should not forget that the greatest efforts for prevention should target lifestyle changes.

The field of biomarkers continues to be dominated by troponins, as seen in the TRAPID-AMI study,43 which was presented at the most recent congress of the European Society of Cardiology. It involved a prospective validation of an algorithm that predicted the determination of ultrasensitive troponin T both at admission and 1 h afterward in a cohort of 1282 individuals who were treated for chest pain in the emergency department. The algorithm was able to rule out ACS in 63.4% of the patients, with a negative predictive value for infarction of 99.1%. The mortality rate in this group of patients was 0.1%, which confirms that this algorithm is safe and effective when used in conjunction with the patient medical history, physical examination, and electrocardiogram.

We have also seen the presentation of new and interesting diagnostic/prognostic point scales that combine clinical variables and biomarkers, such as the BIO-VILCAD44 in chronic CAD and INTERHEART-cholesterol,45 which analyzed a Spanish cohort with chest pain.

Data about the value of membrane microvesicles (particles that are generally derived from platelets) in infarction46 or microRNA in several contexts have expanded the scope of both diagnostic and prognostic studies.47–49 New data have also been published about B-type natriuretic peptide24,26 and copeptin.27 The current state of nontroponin biomarkers is summarized in the Figure and is discussed in extensive detail by Millard and Tranter50 in their excellent review.

Figure.

Hospital mortality (A) and 6-month mortality (B) stratified by type of acute coronary syndrome in the DIOCLES and MASCARA registries; ACS, acute coronary syndrome; DIOCLES: Descripción de la Cardiopatía Isquémica en el Territorio Español; MASCARA: Manejo del Síndrome Coronario Agudo. Registro Actualizado; NSTEACS, non—ST-segment elevation myocardial infarction.

(0.14MB).

As for physiological or imaging techniques, it is important to highlight the publication of consensus documents: one about the definitions of ischemia with various diagnostic methods,51 and another about the criteria for the appropriate use of the different multimodal diagnostic techniques in chronic CAD.52

A prospective study of 3656 patients evaluated the usefulness of additional diagnostic tests after diagnostic ergometry. The diagnostic performance of ergometry was lower in patients with a negative test and those who showed rapid recovery of electrical changes. Meanwhile, it was higher in those who had a clinically positive test (typical angina), even in the absence of electrocardiographic changes, or in patients with positive clinical and electric ergometry.53 Using speckle tracking on stress echocardiography, Peteiro et al54 observed that basal rotation at peak exercise is deteriorated in patients with an ischemic response to exercise. In contrast, apical rotation and torsion are similar to those of patients with normal tests.

In noninvasive angiography by multidetector computed tomography (CT), a new analysis of the ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) study showed that, in patients with chest pain and initially normal electrocardiogram and troponins, the detection of high-risk plaque on multidetector CT was an independent prognostic factor of significant coronary disease, and it was shown to be useful for clinical staging.55 Furthermore, several articles have validated the long-term prognostic value of multidetector CT in patients with suspected CAD.55–57

In nuclear medicine, the combination of single-photon emission CT/CT to determine fractional flow reserve also improved the detection of coronary disease.58 In addition, the SPARC study59 analyzed the 2-year treatment costs in 1703 patients with suspected coronary disease, which were less for single-photon emission CT compared with multidetector CT and positron emission tomography, with no differences in mortality rate. Researchers of the BASKET LATE IMAGING study60 showed the prognostic value of single-photon emission CT for detecting ischemia 5 years after percutaneous revascularization. They indicated that abnormal findings are frequent, regardless of symptoms, and are usually located in regions that had not been treated.

Inducible ischemia, detected with stress cardiac magnetic resonance, was the most powerful predictor for major events in 391 patients with ventricular dysfunction.61 Last of all, the CE-MARC study62 showed higher sensitivity of cardiovascular magnetic resonance compared with single-photon emission CT in 235 women and 393 men with suspected angina; no differences were detected between sexes.

The results of the SIGNIFY63 clinical trial were presented at the most recent congress of the European Society of Cardiology. The study randomly assigned 19 102 patients with stable CAD, without heart failure, and with a heart rate of ≥ 70 beats per minute to receive either ivabradine or a placebo with optimal medical treatment. The primary outcome was a composite of cardiovascular mortality and nonfatal myocardial infarction. The incidence of bradycardia was significantly greater in the ivabradine group (18.0% vs 2.3%; P < .001), and was the main reason for suspending the drug. After a follow-up of 27.8 months, no significant differences were observed in the primary objective between the ivabradine and placebo groups (6.8% vs 6.4%, respectively; HR = 1.08; 95%CI, 0.96-1.20; P = .20). Likewise, no significant differences were found between the ivabradine and placebo groups for the secondary endpoints of cardiovascular death and nonfatal myocardial infarction. In the patients with angina, ivabradine significantly reduced the number of angina episodes (P = .01). However, in patients with Canadian Cardiovascular Society functional class ≥ II, ivabradine significantly increased the incidence of the primary objective (7.6% vs 6.5%; P = .02) while the absolute risk for cardiovascular death and nonfatal myocardial infarction increased by 1.1%. Given these results, it is expected that the indications for ivabradine in stable CAD will be revised.

At the same congress, the 2-year follow-up results were presented from the FAME 2 study.64 In 1220 patients with stable CAD, the fractional flow reserve (FFR) was measured of the stenoses that were visible on angiography. The 888 patients with at least 1 stenosis with an FFR ≤ 0.80 were randomized to either FFR-guided PCI and treatment with medication or medication alone. The primary outcome was a combination of all-cause death, nonfatal myocardial infarction and urgent revascularization. The incidence of the primary endpoint was significantly lower in the PCI group (8.1% vs 19.5%; HR = 0.39; 95%CI, 0.26-0.57; P < .001), basically due to less urgent revascularization in the PCI group, and no significant differences were observed in mortality or nonfatal myocardial infarction. Therefore, in patients with stable CAD, FFR-guided PCI improves results compared with medication alone. Furthermore, in this study, patients with angiographic stenosis and FFR > 0.80 showed good results with drug therapy alone.

Results have been published from an interesting subanalysis of the PLATO study centered around 5366 patients (48.4% of all NSTEACS) managed without revascularization for the first 10 days after randomization.65 Researchers observed a reduction in the risk for ischemic events that was similar to the PCI treatment groups, with no increased risk of hemorrhages.

As for the optimal duration of treatment with dual antiplatelet therapy after ACS, data continue to appear that corroborate the importance of following the recommendation of clinical guidelines and maintaining dual antiplatelet therapy for at least 12 months. The data of a prospective cohort of 56 440 patients with ACS out of the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry66 clearly show an increase in risk of death, stroke and reinfarction (HR = 0.84; 95%CI, 0.75-0.95) in patients who stop dual antiplatelet therapy within 3 months after ACS, compared with those who continued this therapy for more than 3 months. Although the risk for major hemorrhages was higher in patients with longer dual antiplatelet therapy (HR = 1.56; 95%CI, 1.18-2.07), the number of bleeding events in absolute terms was small.

The FAMOUS-NSTEMI study67 randomly assigned 350 patients with NSTEACS to either an FFR-guided revascularization strategy or angiography-guided standard care. The 12-month revascularization rate was higher in the group without FFR, but no differences were seen in quality of life or other events. Fractional flow reserve measurement was associated with a change in treatment for 21.6% of the patients.

With regards to pharmacological innovation, this year there has been a report of the failure of Lp-PLA2 inhibitors (lipoprotein-associated phospholipase A2) to prevent ischemic events after ACS. The VISTA-16 study68 randomized 5145 patients to receive either varespladib (500mg/day) or placebo; treatment was initiated within the first 96h following an ACS and lasted for a duration of 16 weeks. This study was prematurely interrupted due to the lack of effectiveness in the main outcome of cardiovascular death, infarction, stroke or unstable angina, and due to a greater risk of infarction in patients treated with varespladib (3.4%) compared with placebo (2.2%) (HR = 1.66; 95%CI, 1.16-2.39). Results have also been published from the SOLID-TIMI 52 study,69 which compared darapladib (160mg/day) with placebo in 13 026 patients after ACS. Treatment with darapladib did not reduce the incidence of recurrent coronary events (death, infarction, or urgent need for revascularization) compared with placebo: 16.3% and 15.6% at 3 years, respectively (HR = 1.00; 95%CI, 0.91-1.09).

Among the new studies presented within the last year, 2 clinical trials merit comment as they reexamine an old argument: should all the arteries be revascularized during primary PCI or only the culprit artery? The PRAMI study70 attempted to answer this question by randomly assigning 465 patients in 5 hospitals in the United Kingdom to either a complete, preventive revascularization strategy or to revascularization of only the culprit artery. The complete revascularization strategy significantly reduced the primary outcome of death from cardiac causes, nonfatal myocardial infarction, or refractory angina at 2 years, with no differences observed in cardiac death. This strategy was most recently evaluated in another British randomized trial, the CvLPRIT study,71 with only 296 patients. The results were similar in the significant reduction of the primary endpoint (which in this instance also included hospitalizations due to heart failure) with revascularization of all the lesions, although mortality was similar and the benefits obtained were in the reduction of repeat PCI or rehospitalizations.

The new guidelines on myocardial revascularization72 maintain the recommendation of revascularizing only the culprit artery during primary PCI and opting for revascularization that is as complete as possible in patients with shock or persistent ischemia after opening the hypothetical culprit artery (class II indication, level of evidence A). A “staged” revascularization strategy that takes place over several days or weeks continues to be the recommendation for the revascularization of nonculprit lesions in patients with symptoms or inducible ischemia (class II indication, level of evidence A).

Another aspect that is still being analyzed is thrombus aspiration during primary PCI. The 1-year follow-up has been published from the TASTE (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) study,73 which randomly assigned 7244 patients to routine thrombus aspiration or conventional PCI. Routine aspiration did not reduce mortality, the combined primary endpoint, or thrombosis of the stent the first year. The new guidelines for coronary revascularization reduce the indication of thrombus aspiration during primary PCI, which is currently class II, level of evidence B (may be considered in selected patients).72

The ATLANTIC study74 is a double-blind trial that studied the effectiveness and safety of prehospital treatment with ticagrelor in conjunction with acetylsalicylic acid compared with in-hospital administration. It analyzed coronary flow restoration in the blocked artery, resolution of the ST segment, as well as pretreatment safety. The objective of effectiveness, however, was not met. The pretreatment strategy was safe, with a hemorrhage rate that was low and identical to that in the patients with in-hospital ticagrelor treatment. There was a significant reduction in stent thrombosis in the prehospital strategy group. Furthermore, there was a benefit of pretreatment in the patient subgroup not receiving morphine. The most important limitation of this study is undoubtedly the short time interval between drug administration and reperfusion (48min between randomization and angiography; 31min between the 2 loading doses).

This year, 2 Spanish groups have published their results in the field of reperfusion injury. The METOCARD study75 showed a reduction in infarct size with metoprolol treatment before primary PCI in patients with Killip class I or II infarction. A large-scale clinical trial will analyze the impact of this strategy in terms of the reduction of clinical events. Furthermore, the Ischemic Postconditioning on Microvascular Obstruction in Reperfused Myocardial Infarction clinical assay76 studied the role of postconditioning with balloon inflations after the opening of the artery in patients treated with primary PCI. There was no significant difference between the treatment groups in microvascular obstruction or other parameters for myocardial injury measured by cardiovascular magnetic resonance on the fourth day. Interest in this strategy seems to be waning due to the lack of consistent results and objective benefits.

Firstly, we highly recommend the excellent series of review articles about different topics related to critical care that has been published since August 2013 in the New England Journal of Medicine.84

None declared.