Ridker Paul M, Mora Samia, Rose Lynda
The Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA
The Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA.
Eur Heart J. 2016 May 1;37(17):1373-9. doi: 10.1093/eurheartj/ehw046. Epub 2016 Feb 24.
AIMS: Current statin guidelines in Europe and Canada advocate achieving a fixed LDL target or the attainment of a ≥50% reduction in low-density lipoprotein cholesterol (LDLC), while current US guidelines advocate the use of statin therapies that reduce LDLC by <50% (moderate intensity) or ≥50% (high intensity). Data are limited, however, linking the achievement of these % reduction thresholds to subsequent cardiovascular outcomes particularly for contemporary high-intensity regimens. METHODS AND RESULTS: In a randomized trial of 17 082 initially healthy men and women with median baseline LDLC of 108 mg/dL (interquartile range 94-119), we (i) used waterfall plots to assess the variability in LDLC response to rosuvastatin 20 mg daily and (ii) evaluated the impact of reaching ≥50% reductions in LDLC on risk of developing the first cardiovascular events. Among rosuvastatin allocated participants, 3640 individuals (46.3%) experienced an LDLC reduction ≥50%; 3365 individuals (42.8%) experienced an LDLC reduction >0 but <50%; and 851 individuals (10.8%) experienced no reduction or an increase in LDLC compared with baseline. These % LDLC reductions directly related to the risks of first cardiovascular events; at trial completion, incidence rates for the primary endpoint were 11.2, 9.2, 6.7, and 4.8 per 1000 person-years for those in the placebo, no LDLC reduction, LDLC reduction <50%, and LDLC reduction ≥50% groups, respectively. Compared with placebo, the multivariable adjusted hazard ratios for sequentially greater on-treatment per cent reductions in LDLC were 0.91 (95%CI 0.54-1.53), 0.61 (95%CI 0.44-0.83), and 0.43 (95%CI 0.30-0.60) (P < 0.00001). Similar relationships between % reduction and clinical outcomes were observed in analyses focusing on non-HDLC or apolipoprotein B. CONCLUSIONS: As documented for low- and moderate-intensity regimens, variability in % LDLC reduction following high-intensity statin therapy is wide yet the magnitude of this % reduction directly relates to efficacy. These data support guideline approaches that incorporate % reduction targets for statin therapy as well as absolute targets, and might provide a structure for the allocation of emerging adjunctive lipid-lowering therapies such as PCSK9 inhibitors should these agents prove broadly effective for cardiovascular event reduction.
目的：欧洲和加拿大当前的他汀类药物指南提倡实现固定的低密度脂蛋白（LDL）目标或使低密度脂蛋白胆固醇（LDLC）降低≥50%，而美国当前的指南提倡使用使LDLC降低<50%（中等强度）或≥50%（高强度）的他汀类药物治疗。然而，将这些降低百分比阈值的实现与随后的心血管结局联系起来的数据有限，尤其是对于当代高强度治疗方案。 方法和结果：在一项针对17082名初始健康的男性和女性的随机试验中，这些人的基线LDLC中位数为108mg/dL（四分位间距94 - 119），我们（i）使用瀑布图评估每日服用20mg瑞舒伐他汀后LDLC反应的变异性，以及（ii）评估LDLC降低≥50%对首次发生心血管事件风险的影响。在分配接受瑞舒伐他汀治疗的参与者中，3640人（46.3%）的LDLC降低≥50%；3365人（42.8%）的LDLC降低>0但<50%；851人（10.8%）与基线相比LDLC未降低或升高。这些LDLC降低百分比与首次心血管事件的风险直接相关；在试验结束时，安慰剂组、LDLC未降低组、LDLC降低<50%组和LDLC降低≥50%组的主要终点发病率分别为每1000人年11.2、9.2、6.7和4.8例。与安慰剂相比，按治疗期间LDLC依次更大程度降低的多变量调整风险比分别为0.91（95%CI 0.54 - 1.53）、0.61（95%CI 0.44 - 0.83）和0.43（95%CI 0.30 - 0.60）（P < 0.00001）。在关注非高密度脂蛋白胆固醇（non - HDLC）或载脂蛋白B的分析中也观察到降低百分比与临床结局之间的类似关系。 结论：正如低强度和中等强度治疗方案所记录的那样，高强度他汀类药物治疗后LDLC降低百分比的变异性很大，但这种降低百分比的幅度与疗效直接相关。这些数据支持将他汀类药物治疗的降低百分比目标以及绝对目标纳入指南的方法，并且可能为分配新兴的辅助降脂疗法（如前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂）提供一个框架，如果这些药物被证明对降低心血管事件广泛有效。
J Formos Med Assoc. 2017-4
Circ Cardiovasc Qual Outcomes. 2009-11
Gut Microbes. 2024
Pharmaceuticals (Basel). 2024-10-12
Anticancer Agents Med Chem. 2025
Rev Cardiovasc Med. 2023-12-13
J Am Heart Assoc. 2024-3-19
N Engl J Med. 2015-6-3
Arterioscler Thromb Vasc Biol. 2015-4
Zotero 插件