The Trend Is Your Friend: Direct Oral Antagonists as Standard Anticoagulants for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Interventions

In the era of direct oral antagonists (DOACs), both patients and managing physicians have learned to enjoy the benefits this treatment option offers in many clinical scenarios today. Maybe most important for clinical practice, several randomized controlled trials compared safety and efficacy of the various DOACs versus the vitamin-K antagonist (VKA) warfarin in atrial fibrillation (AF) for primary prevention of AF-related stroke, overall showing comparable efficacy in the prevention of stroke, but often higher safety specifically regarding bleeding, while at the same time therapy was easier to handle. However, these first trials generally investigated DOAC anticoagulation monotherapy, which is only one—even though important—aspect for the clinician. Because AF is commonly related with cardiovascular comorbidities and particularly atherosclerosis and coronary artery disease, many patients present with an indication for antiplatelet therapy. At the same time, anticoagulation therapy has been shown essential for AF patients postvascular interventions to prevent stroke or embolic events on top of antiplatelet medication.1 Vice versa, application of both antiplatelet and anticoagulation therapies is linked with increased risk of bleeding.2 Achieving the optimal efficacy on preventing ischemic events and stroke while at the same time avoiding as many bleeding events as possible remains a major clinical challenge in the daily clinical practice. Strikingly, starting with the RE-LY trial reporting numerically higher—even though not statistically significant—rates of myocardial infarction in patients treated with dabigatran compared with VKA, several publications have speculated on possible negative effects of DOAC and/or more specifically dabigatran therapy in the context of acute coronary syndrome, at least in part stating severe concerns.3,4 Meanwhile, despite this alarming trend, large trials also provided convincing evidence that dabigatran therapy most probably reduces all-cause mortality compared with VKA, leaving the physician puzzled when speculating on potential causes and interrelations.5 For an up-to-date summary assessment of this topic complex, we should not forget the lessons learned from COMMANDER heart failure (HF) and COMPASS trials on treating coronary artery disease patients with rivaroxaban.6–8 Here again, the trial results suggest complex interrelations of benefits and risks with the latter trial overall successful when weighing net effects, but the former actually not. Good news first, even in the COMMANDER HF trial, the incidence of nonfatal stroke in the rivaroxaban group was obviously reduced compared with the placebo group [2.0% vs. 3.0%; hazard ratio, 0.66; 95% confidence interval, 0.47–0.95], but this benefit was offset by the increased risk of major bleeding in patients assigned to rivaroxaban compared with the placebo group (3.3% vs. 2.0%; hazard ratio, 1.68; 95% confidence interval, 1.18–2.39). In the COMMANDER HF trial, 34.8% of the enrolled patients received dual antiplatelet therapy at baseline, whereas prior dual antiplatelet therapy was an exclusion criteria of the COMPASS trial. It may thus be speculated that DOACs on top of dual antiplatelet therapy may increase the risk of bleeding in a way the risks may outweigh the benefits. However, weighting ischemic and bleeding risks carefully, the results and conclusions drawn obviously may not be valid for other patient collectives. Recently, the first trials have focused specifically on DOAC therapy in the context of percutaneous coronary interventions (PCI). These patients generally combine a specifically high risk of both thrombosis/ischemia and bleeding and therefore are not well represented in many of the prior DOAC trials. In this issue of the Journal of Cardiovascular Pharmacology, Cordero and colleagues now condense current evidence on the use of DOACs versus VKA in AF patients undergoing PCI, presenting a meta-analysis of these recent trials overall including 11,023 cases. The results suggest overall similar efficacy on preventing cardiac ischemic events and stroke, but a reduction of the incidence of major bleedings by 34% when using DOACs in combination with antiplatelet therapy as compared to VKA.9 While again, the conclusions drawn definitely may not be representative for each patient undergoing PCI, this is an important further step to confirm validity of the general trend to increasingly use DOACs as standard therapy in this scenario, also already condensed in the most recent guidelines. With a still growing range of options for anticoagulation and antiplatelet therapy for mono and combination therapy, designation of the final treatment regime in each patient, however, will still require a meticulous case-based evaluation and careful weighing of the individual benefits and risks by the treating physician.