Using just two anticlotting medicines for patients who have atrial fibrillation and have had a stent placed in a heart artery is safer than using the current standard treatment of three medications, according to a study presented by Brigham and Women's Hospital cardiologist Dr Dr Christopher Cannon, at the European Society of Cardiology Congress 2017.
The RE-DUAL PCI trial, sponsored by Boehringer Ingelheim, found that using the anticoagulant dabigatran along with a second anticlotting drug (clopidogrel or ticagrelor) could reduce risk of major or clinically relevant non-major bleeding compared to using warfarin with aspirin and clopidogrel or ticagrelor. The research team tested two dosages of dabigatran. The risk of bleeding was cut by half for patients who received the 110-mg dose and by one-quarter for those who received the 150-mg dose of dabigatran, compared to warfarin. No increase in cardiac events related to clotting were seen.
"When we treat patients who have atrial fibrillation and need a stent, we need to strike a difficult balance between risk of clotting and risk of bleeding," said Cannon. "Our study finds that patients who received two anticlotting medications – including one of a newer class of drug – had fewer bleeding events without being more at risk for a stroke or other cardiac events."
Each year, approximately 900,000 percutaneous coronary interventions (PCIs) are performed in which a stent is placed in an artery of the heart. About 10% of patients who receive this procedure have atrial fibrillation, a quivering or irregular heartbeat that can lead to blood clots and stroke. Until recently, most guidelines recommended treating these patients with a "triple therapy" that included warfarin and aspirin along with another antithrombotic drug to reduce the risk of stroke. But this has led to high rates of bleeding events.
The RE-DUAL PCI trial set out to test whether a dual antithrombotic therapy – in which aspirin was omitted and dabigatran took the place of warfarin – could safely reduce bleeding events without increasing risk of stroke. The trial was designed and led by an executive steering committee and the sponsor, Boehringer Ingeheim, the manufacturer of dabigatran, in collaboration with an international steering committee.
The trial included 2,725 patients with atrial fibrillation who had undergone stenting. Patients were randomized to receive either the triple therapy with warfarin or the dabigatran double therapy, with two regimens tested using either 110 or 150 mg of dabigatran taken twice daily.
Overall, about 26.9% of patients on the warfarin triple-therapy experienced bleeding, compared to 15.4% of patients on double therapy with the 110-mg dose of dabigatran. About 20.2% of patients on double therapy with the 150-mg dabigatran dose experienced bleeding compared to 25.7% of the corresponding warfarin triple therapy cohort. Stroke and other serious adverse advents didn't differ by group.
Other recent studies have also suggested that dropping aspirin from triple therapy may help to decrease bleeding events. RE-DUAL PCI offers more statistical power than these previous studies.
"These data are very reassuring," said Cannon. "We now have new information to help select the right treatment for individual patients – which has been hard to date, and this study can help."
Dabigatran is part of a new class of anti-coagulants known as NOACs (novel oral anticoagulants). Recent cost comparison analyses of NOACs versus warfarin for treating atrial fibrillation have suggested that while NOACs cost more than warfarin, the use of NOACs can be cost-effective, in part because warfarin requires monthly blood tests and clinician staff time to make adjustments to determine if the drug dosage is appropriate.
Background: Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding.
Methods: In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (≥80 years of age; ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization.
Results: The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups.
Conclusions: Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y12 inhibitor than among those who received triple therapy with warfarin, a P2Y12 inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events.
Christopher P Cannon, Deepak L Bhatt, Jonas Oldgren, Gregory YH Lip, Stephen G Ellis, Takeshi Kimura, Michael Maeng, Bela Merkely, Uwe Zeymer, Savion Gropper, Matias Nordaby, Eva Kleine, Ruth Harper, Jenny Manassie, James L Januzzi, Jurrien M ten Berg, P Gabriel Steg, Stefan H Hohnloser
[link url="https://www.sciencedaily.com/releases/2017/08/170827101743.htm"]Brigham and Women’s Hospital material[/link]
[link url="http://www.nejm.org/doi/full/10.1056/NEJMoa1708454#t=abstract"]New England Journal of Medicine abstract[/link]