p.37 抽出テキスト

6.3.1 Shortening dual antiplatelet therapy

Several RCTs and meta-analyses have compared standard 12-month DAPT with ≤6 months DAPT followed by aspirin monotherapy in ACS patients.264–267 In some of these trials, the reduction in bleeding events associated with abbreviated DAPT regimens came at the cost of an increase in the rates of ischaemic complications. In a large-scale network meta-analysis, 3-month DAPT but not 6-month DAPT was associated with higher rates of MI or stent thrombosis in ACS patients.264 A number of large RCTs have investigated DAPT duration further shortened to 1–3 months followed by P2Y12 receptor inhibitor monotherapy in patients with and without ACS.268–271 In general, low to intermediate ischaemic risk patients were included, and early monotherapy with clopidogrel or ticagrelor was used. Some trials included a comparison with more prolonged DAPT than usual in the control arm. Patients with STEMI tended to be excluded or under-represented. The TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial examined the effect of ticagrelor monotherapy vs. ticagrelor plus aspirin for 1 year after 3 months of DAPT (ticagrelor and aspirin) on clinically relevant bleeding. This study enrolled ‘high-risk’ patients as per the trial inclusion criteria, which meant that the enrolled patients had at least one clinical feature and one angiographic feature associated with a high risk of ischaemic or bleeding events. However, in order to be randomized the patients were also required to have not experienced a major bleeding or ischaemic event in the 3 months following hospital discharge.271 STEMI patients were excluded from this study. Bleeding events (BARC type 2, 3, or 5 bleeding) were significantly reduced by omitting aspirin after 3 months, without a signal of increased ischaemic risk. A dedicated subgroup analysis suggested these findings were consistent in 4614 patients with NSTEMI/UA.272 In the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome) trial, ticagrelor monotherapy vs. ticagrelor plus aspirin for up to 1 year after 3 months of DAPT (ticagrelor and aspirin) was tested in 3056 ACS patients (36% STEMI).273 Net adverse clinical events and major bleeding events were significantly reduced with ticagrelor monotherapy, and major adverse cardiac and cerebrovascular events were not significantly different. Limitations of this study included the selected population assessed and the lower than expected event rates. A study-level meta-analysis of outcomes in a population of patients (with both ACS and CCS) fitted with a DES also reported a beneficial effect of shortened DAPT for 1–3 months on major bleeding events, as well as a neutral effect on death, MI, and stroke.274 The STOPDAPT-2-ACS (ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-2 Study for the Patients With ACS) trial investigated a short DAPT strategy in ACS patients.275 At 1–2 months, patients were randomized to either clopidogrel monotherapy or continued DAPT for 12 months. Non-inferiority of the investigational strategy for the composite endpoint of cardiovascular (CV) or bleeding events was not proven, suggesting that systematic very short duration DAPT (i.e. <3 months) followed by clopidogrel monotherapy is not a useful strategy in ACS patients. The MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial examined a strategy of abbreviated DAPT (1 month) followed by either aspirin or P2Y12 inhibitor monotherapy vs. DAPT ≥3 months (standard therapy) in a cohort of 4579 HBR patients (49% ACS, 12% STEMI) undergoing PCI with a bioabsorbable polymer-coated stent.276 Net adverse clinical events and major adverse cardiac or cerebral events were comparable between the groups, whereas major or clinically relevant non-major bleeding events were significantly reduced in the abbreviated therapy group.

6.3.2 De-escalation from potent P2Y12 inhibitor to

clopidogrel The need to switch between oral P2Y12 receptor inhibitors is not uncommon as a consequence of bleeding complications (or concern regarding bleeding), non-bleeding side effects (e.g. dyspnoea on ticagrelor, allergic reactions), and socioeconomic factors.277,278 As such, switching between oral P2Y12 receptor inhibitors may be considered in selected cases. P2Y12 receptor inhibitor de-escalation (i.e. switching from prasugrel/ ticagrelor to clopidogrel) in ACS patients may be considered as an alternative strategy to the default treatment regimen in order to reduce the risk of bleeding events. However, it is important to note that there is a potential risk of increased ischaemic events with de-escalation and this strategy is not recommended in the first 30 days after the index ACS event. In the TROPICAL-ACS (Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment For Acute Coronary Syndromes) trial (44% NSTE-ACS, 56% STEMI), an approach of DAPT de-escalation from prasugrel to clopidogrel (at 2 weeks after ACS) was guided by platelet function testing and was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit.279 In the Cost-effectiveness of CYP2C19 Genotype Guided Treatment With Antiplatelet Drugs in Patients With ST-segment-elevation Myocardial Infarction Undergoing Immediate PCI With Stent Implantation: Optimization of Treatment (POPular Genetics) trial, DAPT de-escalation from ticagrelor/prasugrel to clopidogrel guided by CYP2C19 genotyping in ACS patients undergoing PPCI within the previous 48 h was non-inferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding.280 The single-centre TOPIC (Timing of Platelet Inhibition After Acute Coronary Syndrome) trial used an unguided de-escalation approach in 645 ACS patients (60% NSTE-ACS, 40% STEMI) from ticagrelor/prasugrel to clopidogrel after 1 month of DAPT with ticagrelor/prasugrel and aspirin. Net adverse clinical events and bleeding events were reduced, whereas the rate of ischaemic endpoints was unchanged.281 The TALOS-AMI (TicAgrelor versus CLOpidogrel in Stabilised Patients with Acute Myocardial Infarction) trial investigated unguided de-escalation in 2697 ACS patients (46% NSTEMI/UA, 54% STEMI) from ticagrelor to clopidogrel after 1 month of DAPT with ticagrelor and aspirin.282 This uniform unguided de-escalation strategy led to significant 12-month reductions in net adverse clinical events and bleeding events. The HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases Trial—Comparison of REDUCTION of PrasugrEl Dose & POLYmer TECHnology in ACS Patients) trial tested a different method of de-escalation—a reduction in prasugrel dose rather than switching to clopidogrel. In this trial, 2338 low-risk ACS patients <75 years of age (14% STEMI, 25% NSTEMI, and 61% UA) were randomized to low-dose prasugrel (5 mg daily) or standard-dose prasugrel (10 mg daily) after 1 month of DAPT with standard-dose prasugrel.283 Prasugrel dose de-escalation was associated with fewer net adverse clinical events and bleeding events, mainly by reducing bleeding events without an increase in ischaemic events. It should be noted that the TALOS-AMI and HOST-REDUCE-POLYTECH-ACS trials only included East Asian populations. Downloaded from academic.oup.com/eurheartj/article/44/38/3720/7243210 by guest on 07 October 2026