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Meta-analysis: Dual therapy yields less bleeding than triple therapy in AF, CAD
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Dual antithrombotic therapy conferred less bleeding but similar rates of mortality, stroke, nonfatal MI and stent thrombosis compared with triple antithrombotic therapy in patients with atrial fibrillation and concomitant CAD, according to a meta-analysis published in The American Journal of Cardiology.
In the meta-analysis, dual therapy with an anticoagulant and a P2Y12 inhibitor was associated with less bleeding risk compared with triple therapy with an anticoagulant, a P2Y12 inhibitor and aspirin (RR = 0.64; 95% CI, 0.54-0.76), but there were no significant differences in mortality, nonfatal MI, stent thrombosis and stroke.
The estimate for heterogeneity was 0% for all outcomes except all-cause mortality.
However, in a subgroup analysis consisting only of trials that used direct oral anticoagulants, researchers observed a borderline significant higher rate of stent thrombosis in the dual therapy group (RR = 1.66; 95% CI, 1.01-2.73), although when patients in the AUGUSTUS trial were removed, the difference in stent thrombosis dissipated (RR = 1.65; 95% CI, 0.82-3.31).
Healio previously reported on the findings of the AUGUSTUS trial from the American College of Cardiology Scientific Session.
“In comparison to triple antithrombotic therapy, dual antithrombotic therapy showed no difference in the outcomes of mortality, nonfatal myocardial infarction and stroke,” Venkatesh Ravi, MD, internist in the division of cardiology at Rush University Medical Center, and colleagues wrote. “Dual antithrombotic therapy also demonstrated a lower incidence of major bleeding.”
The researchers analyzed nine studies in which 6,104 patients received dual therapy and 7,333 patients received triple therapy for the treatment of AF and concomitant CAD (mean age, 73 years; 53.5% with ACS; follow-up varied from 6 to 12 months). Five of the included studies were randomized controlled trials and four were observational studies. Among the randomized controlled trials, three involved direct oral anticoagulants, whereas the other two used a vitamin K antagonist only. Clopidogrel was the most commonly used P2Y12 inhibitor.
“Existing study data demonstrates the safety of dual antithrombotic therapy in terms of reduction in bleeding outcomes with no significant difference in efficacy outcomes, making dual antithrombotic therapy the preferred strategy in patients with AF and concomitant CAD,” the researchers wrote. “However, the potential increase in stent thrombosis is a serious concern when choosing dual antithrombotic therapy for patients at a higher risk of ischemic events.” – by Scott Buzby
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Jay Giri, MD, MPH, FAHA
The meta-analysis aggregates data from trials that have each individually demonstrated higher risks of bleeding with triple therapy than dual therapy. There is no question that long-term use of triple therapy in this patient population is associated with significantly increased risk for bleeding.
The trade-off, of course, is whether patients pay a price in terms of ischemic outcomes (MI and stent thrombosis) with the use of dual therapy. The individual trials comprising the meta-analysis were each underpowered to detect a signal for harm in this regard. However, the current meta-analysis does raise concerns about elevated stent thrombosis rates in patients treated with dual therapy.
The findings are not surprising. It is generally accepted that there is a trade-off between ischemic events and bleeding with more intensive antithrombotic therapy.
Moving forward, the key thing will be to look for factors that influence the risk of ischemic events, especially stent thrombosis, in patients treated with dual therapy. These may be clinical comorbidities, presentation status or anatomic factors associated with the stenting procedure. We then can see whether there is a limited subset of patients in whom short-term triple therapy is justified.
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