抗血小板薬2剤併用療法継続期間に関する論議 (Presentation # 3159)
OPTIDUALトライアルの結果、冠動脈内ステント留置後抗血小板薬2剤併用療法（DAPT）の推奨期間とされている12か月を超えて延長することにより、主要な心有害イベントおよび脳血管イベント（MACCE）は減少しないことが示された。抗血小板薬2剤併用療法の延長により過度の出血がなく虚血性イベントが減少するかもしれない、との兆候が見られていたと研究者らは2015年ESC Congressホットラインセッションで述べた。スタディには、経皮的冠動脈形成術が施行され、安定冠動脈疾患または急性冠症候群のいずれかに対し少なくとも1個の薬剤溶出ステントが留置された1,385人の患者が含まれた。全ての患者が1年間のDAPTを施行され、その後36か月間これを継続する群またはアスピリン単剤に変更し継続する群にランダムに割り付けられた。その結果、主要MACCEエンドポイントに関して有意な群間差は認められなかった（DAPT延長群5.8%対アスピリン単剤群7.5%、p=0.17）。死亡率はDAPT延長群で2.3%であり、アスピリン群では3.5%であった（p=0.18）。しかし、DAPTを延長することにより、ボーダーラインではあるが統計学的に有意でない虚血性イベント（死亡、心筋梗塞、または脳卒中の合計からなるpost-hoc解析）の減少が認められ（DAPT延長群4.2%対アスピリン群6.4% [p=0.006]）、出血が増加したり全死亡率が上昇することはなかった。
An investigator-initiated study showed that extending dual antiplatelet therapy (DAPT, a combination of aspirin and the P2Y12-receptor blocker clopidogrel) beyond the recommended 12 months after coronary stenting does not decrease the rate of major adverse cardiovascular and cerebrovascular events (MACCE). There was, nevertheless, a hint that it might reduce ischemic outcomes without excess bleeding. Results of the trial were presented at a Hot Line session at ESC congress 2015.
"Given the lack of harm and the signal for benefit of prolonged DAPT in the OPTIDUAL trial, and the results from prior randomized trials testing long durations of DAPT, prolongation of DAPT beyond 12 months should be considered in patients without high-risk bleeding, who have received a drug-eluting coronary stent and are event-free at 12 months," said principal investigator Gérard Helft, M.D., Ph.D. from the Institut de Cardiologie, Hôpital Pitié-Salpétrière, in Paris, France.
The OPTIDUAL trial included 1,385 patients from 58 French sites who had undergone percutaneous coronary intervention (PCI) with placement of at least one drug-eluting stent (DES) for either stable coronary artery disease or acute coronary syndrome.
All patients had been on DAPT for one year and were randomly assigned to continue or to remain on aspirin alone for an additional 36 months. The study found no statistical difference between the groups for the primary MACCE endpoint, a composite of all-cause death, myocardial infarction, stroke, and major bleeding (5.8% in the extended-DAPT group and 7.5% in the aspirin only group, p=0.17).
Rates of death were 2.3% in the extended-DAPT group and 3.5% in the aspirin group (p=0.18).
However, there was a borderline but non-statistically significant reduction in ischemic outcomes (a post-hoc outcome composite rate of death, myocardial infarction, or stroke) with extended DAPT (4.2% in the extended-DAPT group and 6.4% in the aspirin group (hazard ratio [HR] 0.64, 95% CI 0.40–1.02, p=0.06) without increased bleeding (2.0% in both groups, p=0.95) or increased all-cause mortality.
The OPTIDUAL trial was designed as a superiority trial, and while it failed to show superiority for extended DAPT, "the results are consistent with the recent findings on ischemic outcomes from the DAPT trial regarding the value of prolonging DAPT after DES placement," said Professor Helft.
"There was no apparent harm, and the post hoc efficacy signal on MACE is consistent with the benefit seen in the DAPT trial. Thus, OPTIDUAL adds to the evidence suggesting benefit to extended DAPT after DES in patients who are event free at 12 months."
Professor Helft commented that the optimal duration of dual antiplatelet therapy after PCI with drug-eluting stent (DES) "is one of the hottest topics in interventional cardiology. The use of DAPT is critically important for the prevention of coronary stent thrombosis, but the optimal duration remains highly debated. This is a major clinical issue, given the large number of patients treated with DES, the costs and risks of antiplatelet therapy, the potentially life-threatening consequences of stent thrombosis and the potential benefits of antiplatelet therapy in preventing ischemic outcomes beyond stent thrombosis."
The study was funded by Assistance Publique - Hôpitaux de Paris and the Fédération Française de Cardiologie, with unrestricted grants from Cordis, Boston, Medtronic, Terumo and Biotronik. Professor Helft reports grants from the French Ministry of Health, the Fédération Française de Cardiologie, Cordis, grants from Boston Scientific, Medtronic, Terumo, and Biotronik. During the conduct of the study he received personal fees from Astra Zeneca, Abbott, Pfizer, Boehringer-Ingelheim, and Bayer, outside of the submitted work.
