Dual antithrombotic therapy an option for AF patients undergoing PCI
In patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), dual antithrombotic therapy with dabigatran and a P2Y12 inhibitor significantly reduces bleeding vs triple therapy with warfarin, a P2Y12 inhibitor and aspirin, with comparable rates of thromboembolic events, results of the RE-DUAL PCI trial have shown.
“Based on these results, dual antithrombotic therapy regimens using doses of dabigatran approved for stroke prevention offer clinicians additional options for managing patients with AF after PCI,” said lead investigator Professor Christopher Paul Cannon of Harvard Medical School, Boston, Massachusetts, US, who presented the study’s results at the European Society of Cardiology Congress 2017 held in Barcelona, Spain. [N Engl J Med 2017, doi: 10.1056/NEJMoa1708454]
In the multicenter study, 2,725 patients with AF were randomized within 120 hours of PCI to receive dual antithrombotic therapy with dabigatran 150 mg BID or 110 mg BID plus a P2Y12 inhibitor (clopidogrel or ticagrelor), or triple therapy with warfarin, a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1–3 months). Elderly patients ≥80 years of age outside the US and those ≥70 years of age in Japan were randomized to receive dabigatran 110 mg BID plus a P2Y12 inhibitor or triple therapy.
After a mean follow-up of 14 months, the primary endpoint of first major or clinically relevant nonmajor bleeding event, as defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria, was reduced by 48 percent with dabigatran 100 mg dual therapy vs warfarin triple therapy (15.4 vs 26.9 percent; p<0.001 for noninferiority and superiority). With dabigatran 150 mg dual therapy, the risk of first ISTH major or clinically relevant nonmajor bleeding event was reduced by 28 percent vs triple therapy (20.2 vs 25.7 percent; p<0.001 for noninferiority).
“The differences between dual therapy and triple therapy emerged early, and widened throughout the duration of the trial,” Cannon reported. “Subgroup analyses showed consistent reductions in ISTH major or clinically relevant nonmajor bleeding with dual therapy in elderly vs nonelderly patients, patients who received clopidogrel or ticagrelor as P2Y12 inhibitor therapy, patients with acute coronary syndrome or stable coronary artery disease, and patients who underwent PCI with drug-eluting or bare metal stents.”
The risk of ISTH major bleeding was reduced by 48 percent and 36 percent in patients who received dual therapy with dabigatran 110 mg [p=0.0003] and 150 mg [p=0.022], respectively, compared with triple therapy.
“Intracranial haemorrhage was reduced by 70 percent in the dabigatran 110 mg arm [0.3 percent vs 1 percent vs triple therapy; p=0.064], and by 88 percent in the dabigatran 150 mg arm [0.1 vs 1 percent; p=0.047],” said Cannon.
The efficacy endpoint – a composite of thromboembolic events (MI, stroke or systemic embolism), death or unplanned revascularization – occurred in 13.7 percent of patients who received dual therapy vs 13.4 percent of patients who received triple therapy (hazard ratio [HR], 1.04; p=0.0047 for noninferiority).
“Dual therapy with dabigatran and a P2Y12 inhibitor was noninferior to warfarin triple therapy in terms of the risk of overall thromboembolic events,” said Cannon.