BARCELONA, SPAIN — Patients with atrial fibrillation (AF) are at lower subsequent risk of bleeding after PCI when treated with dabigatran (Pradaxa, Boehringer Ingelheim) and a P2Y12 inhibitor but not aspirin, according to the results of the RE-DUAL PCI study.
The absolute reduction in major or clinically relevant nonmajor bleeding according to ISTH criteria was 11.5% with 110-mg dabigatran twice daily plus clopidogrel or ticagrelor (Brilinta/Brilique, AstraZeneca) compared with triple therapy with warfarin, clopidogrel or ticagrelor, and aspirin (15.4% vs 26.9%; P<0.001 for noninferiority and superiority).
The absolute risk reduction (ARR) in the primary end point was 5.5% with dabigatran at the 150-mg twice-daily dose vs triple therapy (20.2% vs 25.7%; P<0.001 for noninferiority).
Notably, aspirin therapy was withdrawn after just 1 to 3 months in the study but did not appear to lead to an increase in thrombotic events. After combining the two dual-therapy arms, dabigatran was noninferior to triple therapy for the composite of death, thromboembolic event, or unplanned revascularization (13.7% vs 13.4%).
"Most of the effects, I think, are from taking away aspirin, and it can be safely done, but then some of it is attributable to dabigatran," study author Dr Christopher Cannon (Baim Institute for Clinical Research, Boston, MA) said at the European Society of Cardiology 2017 Congress. The findings were also published online August 27, 2017 in the New England Journal of Medicine.
During a discussion of the results at the ESC, Cannon noted that the ongoing AUGUSTUS trial using apixaban vs warfarin and aspirin vs no aspirin will better tease out the relative contributions of omitting aspirin and the novel oral anticoagulant.
Panelist Prof Georg Nickenig (University Hospital Bonn, Germany) pointed out that in RE-DUAL PCI there was a "huge difference" in the Kaplan Meier curves within the first 3 months but then continuous divergence of the curves, which "argues also for the case of dabigatran that there is less bleeding over time even after aspirin has been stopped in all groups."
Cannon said cardiologists face a clinical conundrum everyday with these patients because AF requires anticoagulation and PCI requires dual antiplatelet therapy (DAPT), but triple therapy is associated with excess bleeding.
Supportive evidence for dropping aspirin has been reported from the 573-patient WOEST study and the more recent PIONEER AF-PCI study utilizing lower doses of rivaroxaban (Xarelto, Bayer/Janssen). But the present study, conducted in 2725 patients from 41 countries, is unique in its statistical power and evaluation of both approved dabigatran doses, noted Cannon.
"These dabigatran dual therapy regimens, using doses of the anticoagulant approved worldwide for stroke prevention, offer all of us clinicians two additional options, with evidence now for managing patients with afib who've undergone PCI," he said.
Clinical guidelines and consensus statements have recommended triple therapy in these patients but have evolved in recent years and now suggest dual antithrombotic therapy is an option, with a class IIb recommendation.
In RE-DUAL PCI, 2725 patients (mean age 70.8 years) with nonvavular AF undergoing PCI received aspirin and other standard therapies for the procedure and were randomized within 5 days (average 1.1 days) into one of the three long-term antithrombotic strategies based on age and location. Because patients aged 80 years or older outside the US and aged 70 years or older in Japan are not eligible for the 150-mg dabigatran dose, 427 elderly patients were assigned to dabigatran 110-mg dual therapy or warfarin triple therapy.
Overall, about 75% of patients were men, a third had diabetes, half had ACS as the indication for PCI, and most received clopidogrel, with only 12% of patients receiving ticagrelor.
In the triple-therapy group, aspirin was given for 1 month after implantation with a bare-metal stent and for 3 months with a drug-eluting stent. The mean time in the target INR range was 64%.
Over a mean follow-up of 14 months, rates of TIMI major bleeding were lower with dual than with triple therapy, as was the rare outcome of intracranial hemorrhage.
There were nonsignificant increases in individual thromboembolic end points in the lower-dose dabigatran arm, but the study was not powered to examine these differences, and the results should be interpreted with caution, the authors write.
Specifically, audience members questioned the higher event rates seen in the dabigatran 110-mg dual therapy arm vs triple therapy for all-cause death (55 vs 48 events) and MI (44 vs 29 events).
"With the withdrawal of aspirin, this is exactly what we would worry about; would there be an increase in thrombotic events?" Cannon responded. "With the lower dose of anticoagulation, there's not a significant increase and there are very small numbers, but it is something to consider when you're looking at a given patient. If someone's very high thrombotic risk, the dabigatran 150 had equal event rates on the efficacy side in the dual-therapy approach and still less major bleeding, so the approach looks good."
Audience members also raised the issue of age when considering which dual therapy regimen to prescribe.
"There was a lot of bleeding, and I think age is a factor that relates to bleeding with dabigatran, although the 110-[mg dose] looked terrific, so I would stay on label," Cannon said.
Nickenig observed that only eight elderly patients in the US were assigned dabigatran 150 mg but said based on the overall results, "I would make a point that it's not a 'you can ' but a 'you should not ' give 150 [mg] to patients above 80, but below 80 it seems to me that's the choice of treatment."
The study was funded by Boehringer Ingelheim. Cannon reports grants and personal fees from Boehringer Ingelheim, Arisaph Pharmaceuticals, Takeda, Bristol-Myers Squibb, Amgen, and Merck; grant support from Janssen and Daichi-Sankyo; and personal fees from Lipimedix, Pfizer, Sanofi, Regeneron, Kowa, Alnylam, Amarin, GlaxoSmithKline, AstraZeneca, and Eisai. Disclosures for the coauthors are listed on the journal website.
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Medscape Medical News © 2017
Cite this: Data Bolster Dual Antithrombotic Therapy in AF PCI Patients - Medscape - Sep 20, 2017.