Lv Han-lu, Jin Dong-mei, Liu Mo, Liu Ying-mei, Wang Jing-feng, Geng Deng-feng
Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Pharmacol Res. 2014 Mar;81:64-73. doi: 10.1016/j.phrs.2014.02.006. Epub 2014 Mar 3.
Large-scale randomized controlled trials (RCTs) have well demonstrated the beneficial effects of cholesterol-lowering treatment with statins in patients at high risk of vascular disease. However, large statin RCTs were usually restricted to the typical 5-6 years. Moreover, non-cardiovascular events, especially the risk of cancer, probably failed to emerge within a restricted period of 6 years. The aim of this study was to evaluate the long-term efficacy and safety of statin treatment by performing a meta-analysis of statin RCTs with extended follow-up beyond 6 years. Six RCTs with post-trial follow-up were eligible for inclusion, involving 47,296 patients with total follow-up ranging from 6.7 to 14.7 years. During the post-trial period, all the surviving participants were advised to take a statin and the cholesterol level were almost identical between the original statin group and the original placebo group. Over the entire 6.7-14.7 years of follow-up, a significant reduction in the rates of all-cause mortality (relative risk 0.90, 95% confidence interval 0.85-0.96; P=0.0009), cardiovascular mortality (0.87, 0.81-0.93; P<0.0001) and major coronary events (0.79, 0.72-0.86; P<0.00001) was observed in favour of the original statin group. During 2-year post-trial period, further reduction in all-cause mortality (0.83, 0.74-0.93; P=0.001), cardiovascular mortality (0.81, 0.69-0.95; P=0.01) and major coronary events (0.77, 0.63-0.95; P=0.01) was observed among initially statin-treated patients. Over the entire follow-up period, statin treatment did not increase the incidence of cancers (0.99, 0.95-1.04; P=0.79), deaths from cancers (1.00, 0.93-1.07; P=0.98) and non-cardiovascular mortality (0.95, 0.90-1.00; P=0.07). In conclusion, statin treatment beyond 6 years is effective and safe in patients at high risk of vascular events. Moreover, earlier treatment with statin may not only preserve the initial benefit but also have further survival benefit for additional 2 years. Further studies are called for to explore the underlying mechanisms.
大规模随机对照试验（RCT）充分证明了他汀类药物降低胆固醇治疗对血管疾病高危患者的有益作用。然而，大型他汀类RCT通常局限于典型的5至6年。此外，非心血管事件，尤其是癌症风险，可能在6年的受限时间内未显现出来。本研究的目的是通过对随访时间超过6年的他汀类RCT进行荟萃分析，评估他汀类治疗的长期疗效和安全性。六项有试验后随访的RCT符合纳入标准，涉及47296名患者，总随访时间为6.7至14.7年。在试验后期间，建议所有存活参与者服用他汀类药物，原他汀类药物组和原安慰剂组的胆固醇水平几乎相同。在整个6.7至14.7年的随访期间，观察到原他汀类药物组全因死亡率（相对风险0.90，95%置信区间0.85 - 0.96；P = 0.0009）、心血管死亡率（0.87，0.81 - 0.93；P < 0.0001）和主要冠状动脉事件（0.79，0.72 - 0.86；P < 0.00001）显著降低。在试验后2年期间，最初接受他汀类治疗的患者全因死亡率（0.83，0.74 - 0.93；P = 0.001）、心血管死亡率（0.81，0.69 - 0.95；P = 0.01）和主要冠状动脉事件（0.77，0.63 - 0.95；P = 0.01）进一步降低。在整个随访期间，他汀类治疗未增加癌症发病率（0.99，0.95 - 1.04；P = 0.79）、癌症死亡率（1.00，0.93 - 1.07；P = 0.98）和非心血管死亡率（0.95，0.90 - 1.00；P = 0.07）。总之，超过6年的他汀类治疗对血管事件高危患者有效且安全。此外，早期使用他汀类药物治疗不仅可能保留初始益处，还可能在额外的2年中有进一步的生存益处。需要进一步研究以探索潜在机制。
