目的:评估用于预防或管理心血管疾病的降脂疗法的益处和危害,包括胆汁酸螯合剂(BAS),ezetimibe,贝多类,烟酸,omega-3补充剂,前蛋白转化酶枯草杆菌蛋白酶-kexin9型(PCSK9)抑制剂,和他汀类药物。
方法:MEDLINE,Cochrane系统评价数据库,和灰色文献搜索。
方法:2017年1月至2022年3月发表的关于他汀类药物的随机对照试验的系统评价,ezetimibe,PCSK9抑制剂,贝多类,BAS,烟酸,选择了用于预防心血管结局的omega-3补充剂.感兴趣的结果包括主要不良心血管事件(MACE),心血管死亡率,全因死亡率,和不良事件。
结果:共纳入76篇系统综述。四个随机对照试验也包括在BAS中,因为没有发现有效性系统评价。他汀类药物显著降低MACE(6篇系统评价;中位风险比[RR]=0.74;四分位距[IQR]=0.71至0.76),心血管死亡率(7篇系统评价;中位RR=0.85,IQR=0.83至0.86),和全因死亡率(8篇系统评价;中位RR=0.91,IQR=0.88~0.92).依泽替米贝也显著减少了主要不良心血管事件(3篇系统评价;中位RR=0.93,IQR=0.93至0.94),PCSK9抑制剂(14篇系统评价;中位RR=0.84,IQR=0.83至0.87),和贝特类药物(2次系统评价;平均RR=0.86),但这些干预措施对心血管或全因死亡率无影响.当添加到他汀类药物中时,贝特类药物对任何心血管结局都没有影响。Omega-3联合补充剂对MACE或全因死亡率没有影响,但显著降低了心血管死亡率(5项系统评价;中位RR=0.93,IQR=0.93至0.94)。单独使用二十碳五烯酸乙酯可显着降低MACE(1项系统评价,RR=0.78)和心血管死亡率(2次系统评价;RR为0.82和0.82)。在初级心血管预防中,只有他汀类药物对MACE表现出一致的益处(6项系统评价;中位RR=0.75,IQR=0.73至0.78),心血管原因死亡率(7篇系统评价,中位数RR=0.83,IQR=0.81至0.90),和全因死亡率(8篇系统评价;中位RR=0.91,IQR=0.87~0.91).
结论:他汀类药物在预防心血管并发症方面具有最一致的证据,MACE的相对风险降低约25%,死亡率降低10%至15%。ezetimibe的加入,PCSK9抑制剂,或二十碳五烯酸乙酯联合他汀类药物可额外降低MACE风险,但对全因死亡率无影响.
To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins.
MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search.
Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events.
A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91).
Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.