ダビガトランを含む2剤併用療法はサブグループ間で一貫して有益である(2017 AHA, Session LBS.05)

RE-DUAL PCI：ダビガトランとP2Y12阻害薬による2剤併用療法は、サブグループ間で一貫してワルファリンよりも出血リスクを減少させる
RE-DUAL PCI: Dual therapy with dabigatran and a P2Y12 inhibitor reduces bleeding risk better than warfarin across subgroups
RE-DUAL PCI試験のサブグループ解析の結果、経皮的冠動脈インターベンション（PCI）を施行される広範な心房細動患者において、ダビガトランとP2Y12阻害薬による2剤併用抗血栓療法は、ワルファリンを含む3剤併用療法に比べ出血リスクが低いことが示された。ダビガトラン2剤併用療法の有益性は、指標となるイベントとしての急性冠症候群の有無に関係なく、薬剤溶出性ステントまたはベアメタルステントを留置され、P2Y12阻害薬、クロピドグレルまたはチカグレロルを投与された患者における主研究の結果と一貫していた。この結果は2017 American Heart Association Scientific Sessions で発表された。
Full Text

A subgroup analysis from the RE-DUAL PCI study found that dual antithrombotic therapy with dabigatran and a P2Y12 inhibitor reduces the risk of bleeding better than triple therapy with warfarin in a range of patients with atrial fibrillation (AF) undergoing PCI.

The benefit of dabigatran dual therapy was consistent with the results from the main study in patients with and without acute coronary syndrome (ACS) as the index event, those receiving drug-eluting stents (DES) or bare-metal stents (BMS), and patients treated with either P2Y12 inhibitor, clopidogrel or ticagrelor.

The RE-DUAL PCI clinical trial, evaluated the safety and efficacy of a dual antithrombotic therapy regimen using dabigatran and a P2Y12 platelet antagonist vs. a triple therapy with warfarin, aspirin and a P2Y12 platelet antagonist. It was a phase IIIb, prospective, randomized trial that enrolled 2725 patients at approximately 550 sites in 41 countries.

The main results were presented at the European Society of Cardiology Congress 2017.  This subgroup analysis presented at the 2017 American Heart Association Scientific Sessions reports outcomes in the major prespecified subgroups including DES versus BMS, acute coronary syndrome (ACS) versus non-ACS, diabetic versus non-diabetic patients, and groups that were age related.

The primary endpoint was time to the first major or clinically relevant non-major bleeding event.  Secondary endpoints were composite of death or thrombotic events and unplanned revascularization; thrombotic events or death; individual outcome events; the composite of death and myocardial infarction or stroke; and unplanned revascularization.

In the RE-DUAL PCI trial

  • The index indication for PCI was an ACS in 50% of the patients
  • DES alone were used in 83% of the patients, similarly in patients with ACS and non-ACS
  • The majority of patients received clopidogrel; 12% of the patients received ticagrelor either as part of dabigatran dual therapy or warfarin triple therapy
  • Patients who received ticagrelor more often had ACS as the index event, were oral anticoagulation naïve, and had DAPT clinical complexity factors; and ticagrelor was associated with higher bleeding risk than clopidogrel
  • There were no significant interactions in any of the presented outcomes for any of the presented subgroups

The main RE-DUAL PCI study showed absolute risk reductions in major or clinically relevant nonmajor bleeding of 11.5% and 5.5% with twice-daily 110-mg and 150-mg dabigatran dual therapy, respectively, compared with triple therapy with warfarin, clopidogrel or ticagrelor, and aspirin.  Dabigatran dual therapy also met the noninferiority threshold for the composite efficacy outcome of death, thromboembolic events, or unplanned revascularization.

The substudy was consistent with the main results for all patient groups.  For example, the new analysis, rates of major or clinically relevant nonmajor bleeding were lower in ACS patients treated with 110-mg (14.7% vs. 27.8%) and 150-mg (20.5% vs 27.1%) dabigatran dual therapy than in those treated with triple therapy.  Similar reductions in these events were observed among non-ACS patients in the 110-mg (16.1% vs. 26.1%) and 150-mg (19.9% vs. 24.4%) dabigatran groups vs. triple therapy.

Similar reductions were seen in patients receiving drug eluting stents, bare metal stents, and patients treated with either P2Y12 inhibitor, clopidogrel or ticagrelor.

"I think it's reassuring that for the majority of patients we can use the higher dose of dabigatran in a dual therapy setting, which is better compared with warfarin triple therapy, which is standard guidelines care," study author Dr. Jonas Oldgren from Uppsala University in Sweden. "For higher-risk, frail patients, we can use the lower dose."

The study was funded by Boehringer Ingelheim.