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RE-DUAL PCI: Dual therapy beneficial in all subgroups in PCI with AF
ANAHEIM, Calif. — Patients with atrial fibrillation who underwent PCI and were treated with dual therapy — dabigatran plus a P2Y12 inhibitor — had consistent benefits across subgroups compared with those treated with triple therapy — warfarin plus a P2Y12 inhibitor plus aspirin.
Subgroups included patients who received either drug-eluting or bare-metal stents, those with and without ACS as an index event, and those with clopidogrel or ticagrelor (Brilinta, AstraZeneca) as their P2Y12 inhibitor.
Jonas Oldgren, head of Uppsala Clinical Research Center and associate professor at the department of medical sciences at Uppsala University in Sweden, and colleagues analyzed data from 2,725 patients with AF who underwent PCI with a bare-metal stent (n = 404) or drug-eluting stent (n = 2,251). Patients were randomized to therapy less than 120 hours after PCI.
Treatments included 150 mg of dabigatran (Pradaxa, Boehringer Ingelheim) twice per day and a P2Y12 inhibitor twice per day; 110 mg of dabigatran twice per day with a P2Y12 inhibitor; or warfarin, a P2Y12 inhibitor and aspirin. Patients were followed up periodically for a mean of 14 months.
As Cardiology Today’s Intervention has previously reported, primary results from the RE-DUAL PCI trial found a 48% reduction in time to first major or clinically relevant non-major bleeding event in patients assigned dual therapy with 110 mg of dabigatran and 28% reduction in patients assigned dual therapy with 150 mg of dabigatran compared with those assigned triple therapy with warfarin.
Researchers compared patients with (n = 1,375; mean age, 71 years; 74% men) and without ACS (n = 1,349; mean age, 71 years; 79% men) in one subgroup analysis.
“They were quite well-balanced despite being a nonrandomized comparison,” Oldgren said.
Events of interest included International Society on Thrombosis and Haemostasis major or clinically relevant non-major bleeding events, TIMI major bleeding and International Society on Thrombosis and Haemostasis major bleeding.
There were no significant interactions, and results in both subgroups were consistent with the main trial results, according to the presentation. Substantial bleeding reductions were seen in patients with and without ACS who were assigned either regimen of dual therapy compared with those assigned triple therapy, Oldgren said.
For the composite of death and thromboembolic events, there were no significant interactions between the two groups. There was a weak trend for a higher risk for MI in patients with ACS who were treated with dual therapy with 110 mg of dabigatran (P = .2) compared with those assigned triple therapy. There was no difference in all-cause death in patients with and without ACS who were treated with any regimen.
“The small number of patients in the BMS group makes major bleeding impossible to compare because with no events in the dabigatran 110 [mg] dual therapy and very small groups for TIMI major bleeding, but consistent with overall results of the study for both dosages,” Oldgren said.
No significant interactions were seen for thromboembolic events or unplanned revascularization for patients with either stent type assigned either dual therapy regimen compared with triple therapy.
Researchers also compared patients who were treated with ticagrelor (n = 327) with those treated with clopidogrel (n = 2,398); the decision about which P2Y12 inhibitor to use was left to the treating physician, Oldgren said. Ticagrelor was used in approximately 12% of patients in the trial.
Results for ticagrelor and clopidogrel were consistent with the main trial results: Though the bleeding risk was lower for patients treated with clopidogrel vs. those with ticagrelor, there were no significant interactions by P2Y12 inhibitor choice, Oldgren said.
There was also no interaction by P2Y12 inhibitor choice for death or thromboembolic events, he said.
“The benefit of the dabigatran dual therapy vs. warfarin triple therapy in patients with atrial fibrillation who underwent PCI was consistent with the main results in patients with ACS and non-ACS at index event, those receiving DES or BMS and patients treated with the P2Y12 inhibitors ticagrelor or clopidogrel,” Oldgren said.
“I do think that subgroups are worth examining, but don’t overinterpret the findings,” Mark A. Hlatky, MD, professor of health research and policy and of cardiovascular medicine at Stanford University, said in a discussant presentation. “Don’t pay attention to the P values in individual subgroups. Instead, pay attention to the P value for interaction to see if the treatment effectiveness varies among subgroups. The interaction P values weren’t significant in RE-DUAL PCI, suggesting the effects of dual therapy were generally consistent.” – by Darlene Dobkowski
Reference:
Oldgren J, et al. LBS.05. New Insights into the Risks, Benefits and Costs of Antithrombotic Therapy. Presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, California.
Disclosures: Oldgren reports he receives consultant and lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer and Sanofi. Hlatky reports no relevant financial disclosures.
Perspective
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The importance of the takeaways from the subgroup analysis is that it’s more like a real-world experience. The conclusions were essentially the same, as the dual therapy and either dose of the dabigatran with the antiplatelet P2Y12 inhibitor — either clopidogrel or ticagrelor — were better for both avoidance of thromboembolic events as well as bleeding events and stent thrombosis than the triple therapy.
Important is that this was also the case in people who had ACS, and in people who had DES or BMS. That didn’t make a difference.
The choice of P2Y12 inhibitor, ticagrelor or clopidogrel, didn’t make a difference either, although some think one may cause more bleeding than another. That wasn’t the case with the subgroup analysis in this study.
These results look very strong. At least three major trials have now shown that dual therapy of an anticoagulant plus an antiplatelet agent without aspirin is superior to triple therapy. This analysis makes that conclusion even stronger, because it shows consistency across subgroups, more like the real-world experience.
This really solidifies that dual therapy is the way to go with patients with AF and PCI that require an anticoagulant, either warfarin or one of the novel oral anticoagulants. In this case, the novel oral anticoagulant was dabigatran. The results suggest that we should not be using triple therapy anymore for anybody, except in select cases.