Efficacy And Safety Of De-escalation Of Anti-platelet Therapy After Percutaneous Coronary Intervention In Patients With Acute Coronary Syndrome:A Meta-analysis Of Randomized Clinical Trials

Background and objective:Strategy of de-escalation,which means switching from potent P2Y₁₂inhibitors to clopidogrel,is recommended as class IIb by European Society of Cardiology.However,there is no definite conclusion on the safety and efficacy of the management.Therefore,we hypothesize this strategy can reduce the incidence of bleeding events while not increasing the incidence of clinical events in patients with acute coronary syndrome（ACS）undergoing percutaneous coronary intervention（PCI）.Methods:We conducted a systematic review and meta-analysis of patients with ACS undergoing PCI,and compared the safety and efficacy of de-escalation or non-de-escalation anti-platelet therapies.The trials were included by searching Cochrane Library,Pub Med,Web of Science,Wanfang,CNKI,and Weipu databases.The inclusion criterion of the study met the following requirements:（1）patients with ACS without age limit;（2）patients received de-escalation therapy from prasugrel or ticagrelor to clopidogrel or continued original P2Y₁₂inhibitions;（3）trials reported the clinical endpoints of ischemic/bleeding events;（4）randomized controlled trials.The exclusion criterion of the study included:（1）duplicate reports;（2）meta-analyses,reviews,or comments;（3）reducing the dose of prasugrel and ticagrelor to de-escalate;（4）trials with incomplete data of outcomes.Net adverse clinical events were identified as the composite endpoint,which was defined as a composite of myocardial infarction,cardiovascular death,revascularization,stroke and bleeding at 12 months after acute coronary syndromes.The efficacy endpoints were myocardial infarction,cardiovascular death,all-cause death,revascularization,stroke and stent thrombosis.Bleeding was designed as the safety endpoint.The fixed effects model was used for risk ratio（RR）and 95%confidence interval（CI）of endpoint events.Results:Six randomized controlled trials with 7627 patients met inclusion criteria.There were significant differences in the risk of net adverse clinical events（RR 0.67,CI 0.58–0.78,P<0.00001）,and bleeding endpoint（0.61,0.52–0.71,P<0.00001）between the two groups.However,there were no significant differences in the risk of cardiovascular death（0.69,0.36–1.32,P=0.26）,myocardial infarction（0.82,0.54–1.24,P=0.34）,revascularization（1.16,0.90–1.51,P=0.25）,stroke（0.59,0.30–1.13,P=0.11）,all-cause death（1,0.56–1.80,P=1.00）and stent thrombosis（1,0.40–2.51,P=1.00）.Conclusions:The strategy of de-escalation from prasugrel or ticagrelor to clopidogrel can reduce the incidence of net adverse clinical events and bleeding events in patients with ACS undergoing PCI（Registered by PROSPERO,CRD42021265782）.