The efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy compared with conventional antiplatelet therapy in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials.
CYP2C19 基因型指导的抗血小板治疗与常规抗血小板治疗在急性冠脉综合征或接受经皮冠状动脉介入治疗患者中的疗效和安全性比较: 随机对照试验的荟萃分析。
- 作者列表："Lyu SQ","Yang YM","Zhu J","Wang J","Wu S","Zhang H","Shao XH","Ren JM
:Cytochrome P450 (CYP) 2C19 genotype is closely associated with the metabolism and efficacy of clopidogrel, thereby having an important impact on clinical outcomes of patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate the efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy in patients with ACS or undergoing PCI. PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify randomized controlled trials (RCTs) comparing CYP2C19 genotype-guided antiplatelet therapy with conventional therapy in patients with ACS or undergoing PCI. Eight RCTs involving 6708 patients were included in this meta-analysis. CYP2C19 genotype-guided antiplatelet therapy was slightly superior to the conventional antiplatelet therapy in reducing the risk of MACE [RR(95%CI): 0.71(0.51-0.98), p = .04]. Meanwhile, the genotype-guided therapy group had significantly lower incidence of myocardial infarction [RR(95%CI): 0.56(0.40-0.78), p < .01], but similar risk of all-cause mortality, cardiovascular mortality, stent thrombosis, urgent revascularization and stroke compared to the conventional therapy group. Incidences of major/minor bleeding and major bleeding were comparable between the two groups. In patients with ACS or undergoing PCI, CYP2C19 genotype-guided antiplatelet therapy displayed benefit over conventional antiplatelet therapy in reducing the risk of MACE and myocardial infarction, without increasing bleeding risk. Further RCTs are needed to provide more evidences for CYP2C19 genotype-guided antiplatelet therapy.
: 细胞色素 P450 (CYP) 2C19 基因型与氯吡格雷的代谢和疗效密切相关，从而对急性冠脉综合征 (ACS) 患者的临床结局产生重要影响或接受经皮冠状动脉介入治疗 (PCI)。本研究旨在评估 CYP2C19 基因型指导的抗血小板治疗在 ACS 或接受 PCI 患者中的有效性和安全性。检索 PubMed 、 EMBASE 、 the Cochrane Library 和 clinicaltrials.gov，确定比较 CYP2C19 基因型指导的 ACS 或 PCI 患者抗血小板治疗与常规治疗的随机对照试验 (rct)。本荟萃分析纳入 8 个 rct，共 6708 例患者。CYP2C19 基因型指导的抗血小板治疗在降低 MACE 风险方面略优于常规抗血小板治疗 [RR(95% CI): 0.71(0.51-0.98)，p =。04]。同时，基因型指导治疗组心肌梗死发生率明显降低 [RR(95% CI): 0.56(0.40-0.78)，p <.01]，但与常规治疗组相比，全因死亡率、心血管死亡率、支架内血栓形成、紧急血运重建和卒中的风险相似。两组主要/次要出血和主要出血的发生率相当。在 ACS 或接受 PCI 的患者中，CYP2C19 基因型指导的抗血小板治疗在降低 MACE 和心肌梗死风险方面显示出优于常规抗血小板治疗，而不增加出血风险。需要进一步的 rct 为 CYP2C19 基因型指导抗血小板治疗提供更多的证据。
METHODS:BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. METHODS: 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. RESULTS: Compared with no GPI (n = 930), routine GPI (n = 525) or bailout GPI (n = 175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p = 0.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32-6.64; p = 0.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88-3.61; p = 0.92). CONCLUSION: Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation.
METHODS:OBJECTIVES:There are limited data on bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) with positive biomarkers of myocardial necrosis (troponin and/or creatine kinase-myocardial band isoenzyme). We sought to evaluate the safety and efficacy of bivalirudin monotherapy in patients with positive biomarkers from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. PATIENTS AND METHODS:We compared the net adverse clinical events [composite ischemia - (death, myocardial infarction, or unplanned ischemic revascularization) - or noncoronary artery bypass graft surgery (CABG)-related major bleeding] among patients with biomarker-positive NSTE-ACS in the ACUITY trial overall and by antithrombotic strategy. RESULTS:Among 13 819 patients with NSTE-ACS enrolled in ACUITY, 4728 patients presented with positive biomarkers and underwent an early invasive strategy. Of those, 1547 were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), 1555 to bivalirudin plus GPI, and 1626 to bivalirudin monotherapy. Compared with biomarker-negative patients, biomarker-positive patients had higher 30-day rates of net adverse clinical events (14.0 vs. 12.4%; P = 0.04), all-cause death (1.3 vs. 0.5%; P = 0.001), cardiac death (1.1 vs. 0.5%; P = 0.005), and non-CABG-related major bleeding (6.5 vs. 5.2%, P = 0.03). At 30 days, bivalirudin monotherapy was associated with significantly less non-CABG-related major bleeding (bivalirudin monotherapy 4.1% vs. bivalirudin plus GPI 8.4% vs. heparin plus GPI 7.1%) with comparable rates of composite ischemia (bivalirudin monotherapy 9.2% vs. bivalirudin plus GPI 9.9% vs. heparin plus GPI 8.4%). In a multivariable model, bivalirudin monotherapy was associated with a significant reduction in non-CABG-related major bleeding but was not associated with an increased risk of death, myocardial infarction, unplanned revascularization or stent thrombosis. CONCLUSION:Compared with heparin plus GPI or bivalirudin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding at 30 days among patients with NSTE-ACS and positive biomarkers.
METHODS:Atrial fibrillation (AF) and concomitant coronary artery disease (CAD) create a therapeutic dilemma as the risk of bleeding with triple antithrombotic therapy (TATT) must be balanced against the risk of ischemic events with double antithrombotic therapy (DATT). The aim of this meta-analysis is to compare the efficacy and safety of DATT versus TATT in AF and CAD. MEDLINE, Cochrane, and ClinicalTrials.gov databases were searched for relevant articles published from inception to May 1, 2019. Studies comparing the safety and efficacy of DATT versus TATT in patients with AF and CAD were included. Among 9 studies, where 6,104 patients received DATT and 7,333 patients received TATT, there was no statistically significant difference in the outcomes of mortality, nonfatal myocardial infarction, stent thrombosis, and stroke. There was a lower rate of major bleeding in DATT (risk ratio [RR] 0.64 [95% confidence interval [CI] 0.54 to 0.75]; p <0.001). There was no significant difference in stent thrombosis (RR 1.52 [95% CI 0.97 to 2.38]; p = 0.07). However, subgroup analysis of trials with direct oral anticoagulant use demonstrated a borderline higher rate of stent thrombosis in DATT (RR 1.66 [95% CI 1.01 to 2.73]; p = 0.05). In conclusion, DATT showed no difference in the outcomes of mortality, stroke, nonfatal myocardial infarction, and stent thrombosis compared with TATT. DATT demonstrated a lower rate of major bleeding. DATT demonstrated a borderline higher rate of stent thrombosis in the subgroup analysis of trials with direct oral anticoagulant which needs to be evaluated in further studies.