The number of patients requiring surgery is increasing, and is now estimated at more than 300 million per year.1 Because of longer life expectancy, patients who undergo an invasive procedure are often under chronic antithrombotic therapy before the intervention.2 In Spain, around 1 million individuals take chronic anticoagulants, mainly for atrial fibrillation (AF), and the number is rising because of population aging and an increase in risk factors.3 In addition, there has been an upsurge in antiplatelet therapy for secondary prevention of atherothrombotic disease, in keeping with the increase in percutaneous coronary interventions (PCIs) and studies recommending prolonged use of these agents.4–7 To avoid periprocedural adverse events, it is important to determine whether and exactly when it is appropriate to interrupt antithrombotic therapy. The decision to withdraw or maintain these drugs is determined by the interaction between the patient's thrombotic risk and the bleeding risk associated with the intervention.8–10

In an attempt to simplify clinical decision-making, various guidelines and position papers have been published on perioperative management of antithrombotic drugs in several clinical scenarios.11–18 These include a consensus document on perioperative/periprocedural management of these drugs coordinated by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology and certified by more than 20 Spanish scientific societies.19 Despite the existence of recommendations, little is known about their real-world impact on patients receiving anticoagulant or antiplatelet drugs and requiring an intervention. The aim of this study was to analyze antithrombotic therapy management in patients undergoing surgery or another invasive procedure, and evaluate the effect of interrupting or maintaining this therapy on the incidence of adverse cardiovascular and bleeding events.

The REQXAA registry (Spanish registry on perioperative/periprocedural management of anticoagulant and antiplatelet drugs) is a prospective, observational, multicenter, multispecialty study with clinical follow-up of patients receiving antithrombotic therapy (antiplatelet agents or anticoagulants) and requiring surgery or another invasive procedure.

The results of the Spanish REQXAA registry, which provide an analysis of patients on chronic anticoagulant or antiplatelet therapy requiring surgery or another invasive procedure, indicate that real-world adherence to the current consensus recommendations for perioperative management of these drugs is low. Of particular note, patients whose periprocedural antithrombotic therapy management was deemed inappropriate had a more than 2-fold higher risk of experiencing an adverse ischemic or bleeding event after the intervention (figure 4).

Figure 4.

Central illustration. Results of the REQXAA study: prospective observational registry of real-world perioperative and periprocedural antithrombotic therapy management.

(0.66MB).

The increase in patients on chronic therapy with anticoagulant and antiplatelet agents who may require an invasive procedure during their lifetime has led several scientific societies to publish consensus and position papers on the management of these drugs.11–18 However, many of the recommendations in these documents are limited by a lack of scientific evidence; hence, their application in clinical practice may be heterogeneous. It is important to determine not only the degree of adherence to these recommendation, but also whether proper adherence is associated with a lower incidence of adverse events following the procedure.

The literature contains very few registries analyzing local implementation of protocols for perioperative antithrombotic therapy. Rossini et al.13,22 evaluated the impact of an Italian consensus document for periprocedural management of antiplatelet therapy. Adherence to the Italian recommendations was as high as 85%, although the study was not designed to determine whether their application was associated with fewer cardiovascular events. This result contrasts with the findings of our registry, in which management was in accordance with the recommendations of the Spanish consensus document in only 57.3% of the patients. The percentage differed depending on the patients’ antithrombotic therapy: adherence was lower in patients receiving anticoagulants (49.1%) than in those using antiplatelet agents (62.1%). The finding that antithrombotic drug management was inappropriate according to the recommendations in almost half the patients is even more striking considering that the cohort's overall risk was low. Among the total, 12.7% of patients had a high thrombotic risk and 14.1% a high bleeding risk, and in general, the published recommendations for these patients are more controversial, as they require individualizing the antithrombotic therapy. There are several reasons for the differences observed. Dose adjustment is more difficult with anticoagulant drugs (eg, previous INR values with acenocoumarol or warfarin, renal function with DOACs) than with antiplatelet agents. In the latter case, especially in patients receiving aspirin monotherapy at a dose <150mg/d (most patients included in our registry) and with a previous PCI, most recommendations agree that this therapy should be maintained during the perioperative period.23,24

One of the main causes of inappropriate perioperative and periprocedural antithrombotic drug management is overuse of bridging therapy, which has been associated with a higher incidence of adverse events, in particular bleeding.25 Ferrandis et al.26 performed a study in patients receiving chronic DOAC therapy and requiring major surgery. Bridging therapy, administered to 35% of the patients, was associated with a higher incidence of bleeding events, with no difference in thrombotic events. These findings are supported by the results of a study by Douketis et al., 27 including more than 3000 DOAC-treated patients with nonvalvular AF who underwent surgery or another procedure. A strategy without bridging therapy used in that study yielded lower rates of thromboembolic and bleeding events. Evidence that bridging therapy may lack effectiveness has been reported in relation to some procedures, such as pulmonary vein ablation in AF patients and in certain situations outside the perioperative period (eg, following a stroke and before starting DOACs).28,29 These findings could add to the controversy around periprocedural antithrombotic management. In our registry, 18.8% of patients overall were administered perioperative bridging therapy, a value that rose to 35.3% in patients receiving anticoagulants.

In the present study, most patients had a low thrombotic and bleeding risk, but the 30-day incidence of the main outcome measure was 7.6%, which is not as low as might be expected. It is important to draw attention to this finding, in light of the large number of patients on antithrombotic therapy who require surgery at some point in their lives. In the statistical analysis, inappropriate perioperative antithrombotic management and high thrombotic risk were the 2 independent risk factors for some type of adverse event to occur within the first 30 days after the intervention. This finding underscores the importance of proper adherence to the recommendations, and not only in high-risk patients, to reduce the incidence of adverse events.

The results of the REQXAA registry have brought to light the limited real-world implementation of the consensus recommendations of various scientific societies for the management of perioperative antithrombotic therapy. Furthermore, inappropriate management in this context was found to be associated with an increased incidence of adverse ischemic and bleeding events. It is essential to insist on proper management of antiplatelet and anticoagulant therapy by adhering to local protocols to reduce perioperative complications.

No funding received.

D. Vivas and M. Anguita-Gámez contributed equally to the manuscript. All authors met the following requirements: 1) they contributed substantially to the conception and design of the study, and acquisition, analysis or interpretation of the data, 2) they participated in writing the article or critically reviewing its intellectual content, 3) they approved the final version to be published, and 4) they agreed to take responsibility for all aspects of the article and to investigate and resolve any issues related to the accuracy and veracity of the contents.

D. Vivas: presentation fees from Daiichi Sankyo, AstraZeneca, Bayer, Pfizer, Abbott, Boehringer Ingelheim, Bristol-Myers-Squibb and Ferrer. R. Ferrandis: presentation fees from LFB, CSL Behring and Octapharma. M. Anguita: presentation fees from Eli Lilly & Co, Daiichi Sankyo, AstraZeneca, Bayer, Pfizer, Boehringer Ingelheim, Bristol-Myers-Squibb and Novartis; consultancy work for Eli Lilly & Co, Daiichi Sankyo, AstraZeneca, Bayer, Pfizer, Boehringer Ingelheim, Bristol-Myers-Squibb and Novartis. I. Egocheaga: presentation fees from Boehringer Ingelheim, AstraZeneca; consultancy work for AstraZeneca; support for conference attendance from Novartis. A. Abad-Motos: support for conference attendance from Vifor, Edwards. E. Figuero: presentation fees from Oral-B, Colgate, Johnson & Johnson, Spanish Society of Periodontology (SEPA), Irish Society of Periodontology, Ukrainian Association of Periodontology, French Dental Association of Periodontology; research grants from Dentaid, Lacer, Universidad de Bristol; support for attending conferences from SEPA, European Federation of Periodontology, Irish Society of Periodontology and French Dental Association of Periodontology. N. Bouzó-Molina: support for conference attendance from MSD. J. Torres: presentation fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly & Co, Novartis, Pfizer and Rovi. M.J. Descalzo: presentation fees from GlaxoSmithKline; support for conference attendance from Daiichi Sankyo. E. Martín-Rioboo: presentation fees from Servier, Ferrer, Boehringer Ingelheim. F. Marín: presentation fees from AstraZeneca and Boehringer Ingelheim; consultancy work for Boehringer Ingelheim; research grants from AstraZeneca, Ferrer and BMS; support for attending conferences from Esteve and Novo Nordisk; participation in advisory committees or monitoring of AFNET security data. All other authors declare they have no conflicts of interest.

The Coordinating Committee of the REQXAA Registry would like to thank all the researchers (supplementary data) who participated in enrolling patients in the study.