Department of Primary and Long-term Care, University of Groningen, University Medical Centre Groningen, PO Box 196, 9700 AD, Groningen, The Netherlands.
Am J Cardiovasc Drugs. 2024 Nov;24(6):743-752. doi: 10.1007/s40256-024-00668-y. Epub 2024 Aug 14.
Despite the effect on blood lipid levels, the clinical benefits of intensive versus standard pharmacological lipid-lowering therapy remain unclear. Previous reviews have presented relative effects on the risk of clinical outcomes, but not the absolute risk reductions (ARRs) and the time gained to a clinical outcome, also called outcome postponement (OP). The aim of this study was to estimate the effect of intensive versus standard lipid-lowering therapy in terms of ARR and OP of major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and all-cause mortality.
We searched PubMed, Embase, and prior reviews to identify trials comparing intensive versus standard lipid-lowering therapy for the risk of cardiovascular disease. We extracted the number of patients with MACE, MI, stroke, and all-cause mortality. Risk of bias was assessed according to the five domains of the Cochrane Risk of Bias Tool 2.0. We calculated ARRs and OPs to assess the clinical benefits of intensive versus standard therapy for each outcome. We conducted meta-analyses standardizing the results to 2 and 5 years of follow-up.
We identified 11 double-blind, randomized, controlled trials (n = 101,357). The follow-up period ranged from 1.5 to 7.0 years, with an average follow-up duration of 3.7 years. Risk of bias was generally high. During an estimated 2 years of intensive versus standard lipid-lowering therapy, 1.1% (95% confidence interval [CI] 0.7-1.5) fewer patients had MACE and the OP of MACE was 4.1 days (95% CI 2.6-5.6). The effects were 0.7% (95% CI 0.4-0.8) and 2.5 days (95% CI 1.6-3.3) for MI, 0.2% (95% CI 0.1-0.3) and 0.9 days (95% CI 0.5-1.2) for stroke, and 0.2% (95% CI - 0.1 to 0.4) and 0.6 days (95% CI - 0.4 to 1.5) for all-cause death. During on average 5 years of intensive versus standard lipid-lowering therapy, 2.4% (95% CI 1.5-3.3) fewer patients had MACE and the time gained to MACE was 23.5 days (95% CI 14.9-32.0). The effects were 1.5% (95% CI 1.0-2.1) and 14.6 days (95% CI 9.3-20.0) for MI, 0.6% (95% CI 0.4-0.8) and 5.3 days (95% CI 3.3-7.4) for stroke, and 0.4% (95% CI -0.2 to 0.1) and 3.6 days (95% CI - 2.1 to 9.2) for all-cause death.
Intensive lipid-lowering therapy during 2 or 5 years did not lead to fewer deaths or lifetime gained, and the effects on MI and stroke were negligible. The largest effect was that MACE did not occur in two of 100 patients and was postponed 3-4 weeks after 5 years of intensive treatment. Given the small effect, patients should receive this information as part of shared decision making.
尽管降脂治疗对血脂水平有影响，但强化与标准药物降脂治疗的临床获益仍不明确。先前的综述报告了对临床结局风险的相对影响，但未报告绝对风险降低（ARR）和获得临床结局的时间，也称为结局推迟（OP）。本研究旨在评估强化与标准降脂治疗在主要不良心血管事件（MACE）、心肌梗死（MI）、卒中和全因死亡率的 ARR 和 OP 方面的效果。
我们检索了 PubMed、Embase 和先前的综述，以确定比较强化与标准降脂治疗心血管疾病风险的试验。我们提取了 MACE、MI、卒中和全因死亡率的患者数量。根据 Cochrane 偏倚风险工具 2.0 的五个领域评估了风险偏倚。我们计算了 ARR 和 OP，以评估强化与标准治疗对每个结局的临床获益。我们进行了荟萃分析，将结果标准化为 2 年和 5 年的随访。
我们确定了 11 项双盲、随机、对照试验（n=101357）。随访时间从 1.5 年到 7.0 年不等，平均随访时间为 3.7 年。风险偏倚普遍较高。在估计的 2 年强化与标准降脂治疗期间，有 1.1%（95%置信区间[CI]0.7-1.5）的患者发生 MACE，MACE 的 OP 为 4.1 天（95% CI 2.6-5.6）。效果为 0.7%（95% CI 0.4-0.8）和 2.5 天（95% CI 1.6-3.3）用于 MI，0.2%（95% CI 0.1-0.3）和 0.9 天（95% CI 0.5-1.2）用于卒中和 0.2%（95% CI -0.1 至 0.4）和 0.6 天（95% CI -0.4 至 1.5）用于全因死亡。在平均 5 年强化与标准降脂治疗期间，有 2.4%（95% CI 1.5-3.3）的患者发生 MACE，获得 MACE 的时间延长了 23.5 天（95% CI 14.9-32.0）。效果为 1.5%（95% CI 1.0-2.1）和 14.6 天（95% CI 9.3-20.0）用于 MI，0.6%（95% CI 0.4-0.8）和 5.3 天（95% CI 3.3-7.4）用于卒中和 0.4%（95% CI -0.2 至 0.1）和 3.6 天（95% CI -2.1 至 9.2）用于全因死亡。
强化降脂治疗 2 年或 5 年不会导致死亡或寿命减少，对 MI 和卒中的影响可以忽略不计。最大的效果是 100 名患者中有 2 名不会发生 MACE，并且在强化治疗 5 年后 3-4 周才出现 MACE。考虑到影响较小，患者应将此信息作为共同决策的一部分。
