LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial.
使用 evolocumab 降低 LDL-胆固醇，以及 FOURIER 试验中患者的年龄和性别结局。
- 作者列表："Sever P","Gouni-Berthold I","Keech A","Giugliano R","Pedersen TR","Im K","Wang H","Knusel B","Sabatine MS","O'Donoghue ML
AIMS:Some trials have reported diminished efficacy for statins in the elderly, and in women compared with men. We examined the efficacy and safety of evolocumab by patient age and sex in the FOURIER trial, the first major cardiovascular outcome trial of a PCSK9 inhibitor. METHODS AND RESULTS:FOURIER was a randomised, double blind trial, comparing evolocumab with placebo in 27,564 patients with atherosclerotic cardiovascular disease receiving statin therapy (median follow-up 2.2 years). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina or coronary revascularisation. Cox proportional hazards models were used to assess the efficacy of evolocumab versus placebo stratified by quartiles of patient age and by sex. There were small variations in the cardiovascular event rate across the age range (for the primary endpoint, Kaplan-Meier at 3 years 15.6%, >69 years, vs. 15.1%, ≤56 years, P = 0.45); however, the relative efficacy of evolocumab was consistent regardless of patient age (for the primary endpoint (Q1 hazard ratio, 95% confidence interval) 0.83, 0.72-0.96, Q2 0.88, 0.76-1.01, Q3 0.82, 0.71-0.95, Q4 0.86, 0.74-1.00; Pinteraction = 0.91), and the key secondary endpoint (cardiovascular death, myocardial infarction, stroke) (Q1 0.74 (0.61-0.89), Q2 0.83 (0.69-1.00), Q3 0.78 (0.65-0.94), Q4 0.82 (0.69-0.98)); Pinteraction = 0.81). Women had a lower primary endpoint rate than men (Kaplan-Meier at 3 years 12.5 vs. 15.3%, respectively, P < 0.001). Relative risk reductions in the primary endpoint and key secondary endpoint were similar in women (0.81 (0.69-0.95) and 0.74 (0.61-0.90), respectively) compared with men (0.86 (0.80-0.94) and 0.81 (0.73-0.90), respectively), Pinteraction = 0.48 and 0.44, respectively. Adverse events were more common in women and with increasing age but, with the exception of injection site reactions, there were no important significant differences reported by those assigned evolocumab versus placebo. CONCLUSIONS:The efficacy and safety of evolocumab are similar throughout a broad range of ages and in both men and women.
目的: 一些试验已经报道他汀类药物在老年人和女性中的疗效与男性相比有所降低。我们在第一个 PCSK9 抑制剂的主要心血管结局试验 FOURIER 试验中，通过患者年龄和性别检验了 evolocumab 的疗效和安全性。 方法和结果: FOURIER 是一项随机、双盲试验，在接受他汀类药物治疗的 27,564 例动脉粥样硬化性心血管疾病患者中比较 evolocumab 与安慰剂 (中位随访时间 2.2 年)。主要终点是心血管死亡、心肌梗死、卒中、因不稳定型心绞痛住院或冠状动脉血运重建。使用 Cox 比例风险模型评估 evolocumab 与安慰剂的疗效，按患者年龄和性别分层。在整个年龄范围内，心血管事件发生率存在微小差异 (对于主要终点，3 年时 Kaplan-Meier 为 15.6%，> 69 岁，vs。 15.1%，≤ 56 年，p = 0.45); 然而，evolocumab 的相对疗效与患者年龄无关 (对于主要终点 (Q1 风险比,95% 置信区间) 0.83，0.72-0.96，Q2 0.88，0.76-1.01，Q3 0.82，0.71-0.95，Q4 0.86，0.74-1.00; Pinteraction = 0.91), 和关键次要终点 (心血管死亡、心肌梗死、卒中) (Q1 0.74 (0.61-0.89)，Q2 0.83 (0.69-1.00)，Q3 0.78 (0.65-0.94), q4 0.82 (0.69-0.98));Pinteraction = 0.81)。女性的主要终点率低于男性 (3 年时 Kaplan-Meier 分别为 12.5 vs.15.3%，p
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.