Clinical Pharmacology and Therapeutics, Imperial College London, International Centre for Circulatory Health, 59 North Wharf Road, London W2 1PG, UK.
Eur Heart J. 2011 Oct;32(20):2525-32. doi: 10.1093/eurheartj/ehr333. Epub 2011 Aug 28.
The aim of this study was to determine the outcome benefits in those originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-8 years after closure of the lipid-lowering arm (LLA) of the trial (ASCOT-LLA) among the U.K. population.
ASCOT-LLA was a factorially designed double-blind placebo-controlled trial of atorvastatin in 10 305 hypertensive patients enrolled into the ASCOT-Blood Pressure Lowering Arm (BPLA) of the trial and with total cholesterol concentrations, at baseline, of <6.5 mmol/L. ASCOT-LLA was stopped prematurely after a median 3.3-year follow-up because of a 36% relative risk reduction (RRR) in non-fatal myocardial infarction and fatal coronary heart disease (CHD) (the primary outcome) in favour of atorvastatin and a non-significant reduction in CV deaths (16%) and all-cause mortality (13%). After a further 2.2 years at the end of ASCOT-BPLA, despite extensive crossovers from and to statin usage, the RRR in all endpoints remained essentially unchanged. A median 11 years after initial randomization and ∼8 years after closure of LLA, all-cause mortality (n=520 and 460 in placebo and atorvastatin, respectively) remained significantly lower in those originally assigned atorvastatin (HR 0.86, CI 0.76-0.98, P=0.02). CV deaths were fewer, but not significant (HR 0.89, CI 0.72-1.11, P=0.32) and non-CV deaths were significantly lower (HR 0.85, CI 0.73-0.99, P=0.03) in those formerly assigned atorvastatin attributed to a reduction in deaths due to infection and respiratory illness.
Legacy effects of those originally assigned atorvastatin may contribute to long-term benefits on all-cause mortality. An explanation for long-term benefits on non-CV deaths has not been established.
本研究旨在确定在 ASCOT-LLA（ASCOT 降脂臂试验）降脂治疗臂关闭 8 年后，最初接受阿托伐他汀治疗的英国人群的结局获益。
ASCOT-LLA 是一项阿托伐他汀的因子设计、双盲、安慰剂对照试验，共纳入了 10305 例高血压患者，这些患者均来自 ASCOT 血压降低臂（ASCOT-BPLA）试验，且基线时总胆固醇浓度<6.5mmol/L。由于阿托伐他汀治疗组非致死性心肌梗死和致死性冠心病（主要终点）的相对风险降低了 36%（RRR），ASCOT-LLA 提前终止，随访中位数为 3.3 年，而心血管死亡（16%）和全因死亡率（13%）无显著降低。在 ASCOT-BPLA 结束后的另外 2.2 年，尽管有大量患者从他汀类药物转为他汀类药物治疗，但所有终点的 RRR 基本保持不变。在最初随机分组后 11 年，即降脂治疗臂关闭后约 8 年，最初接受阿托伐他汀治疗的患者的全因死亡率（分别为安慰剂组 520 例和阿托伐他汀组 460 例）仍显著降低（HR 0.86，95%CI 0.76-0.98，P=0.02）。心血管死亡率虽较低，但无统计学意义（HR 0.89，95%CI 0.72-1.11，P=0.32），而非心血管死亡率显著降低（HR 0.85，95%CI 0.73-0.99，P=0.03），归因于感染和呼吸系统疾病导致的死亡率降低。
最初接受阿托伐他汀治疗的患者可能会产生长期的获益，这可能是长期全因死亡率降低的原因。非心血管死亡率长期获益的原因尚未确定。
