服用他汀类药物的益处受到质疑:

高胆固醇和心脏病之间的联系“不一致”

诸平

据爱尔兰RCSI医学与健康科学大学（RCSI University of Medicine and Health Sciences）2022年3月14日提供的消息，RCSI医学与健康科学大学的一项新研究显示，“坏”胆固醇——也就是低密度脂蛋白胆固醇（Low-Density Lipoprotein Cholesterol简称LDL-C)与心脏病和中风等不良健康结果之间的联系可能不像之前认为的那样强烈。相关研究结果于2022年3月14日已经在《美国医学会内科杂志》（JAMA Internal Medicine）杂志网站发表——Paula Byrne, Maryanne Demasi, Mark Jones, Susan M Smith, Kirsty K O'Brien, Robert DuBroff. Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis. JAMA Internal Medicine, 2022 Mar 14. DOI: 10.1001/jamainternmed.2022.0134. https://pubmed.ncbi.nlm.nih.gov/35285850/

参与此项研究的除了爱尔兰RCSI医学与健康科学大学的研究人员之外，还有来自丹麦哥本哈根的科学自由研究所（Institute for Scientific Freedom, Copenhagen, Denmark）、澳大利亚昆士兰邦德大学（Bond University, Robina, Queensland, Australia）、爱尔兰都柏林的三一学院（Trinity College Dublin, Dublin, Ireland）、美国阿尔伯克基的新墨西哥大学（University of New Mexico, Albuquerque, USA）的研究人员以及来自爱尔兰都柏林的独立研究者（Independent researcher, Dublin, Ireland）。

这项研究质疑他汀类药物在降低LDL-C、从而降低心血管疾病(cardiovascular disease简称CVD)风险的情况下的疗效。

之前的研究表明，使用他汀类药物降低LDL-C对健康有积极影响，这反映在预防心血管疾病的专家指南的各种迭代中。根据之前的研究，现在医生通常会开他汀类药物，50岁以上的爱尔兰成年人中有三分之一在服用他汀类药物。

新的发现反驳了这个理论，发现这种关系并不像之前认为的那样牢固。相反，研究表明，使用他汀类药物降低LDL-C对心肌梗死(myocardial infarction简称MI)、中风（stroke）和全因死亡率（all-cause mortality）等CVD结果有不一致和不确定的影响。

此外，这表明服用他汀类药物的总体效益可能很小，并且会因个人的风险因素而有所不同。

这篇论文的主要作者是来自CRST的全科医学系（RCSI’s Department of General Practice）的HRB初级保健研究中心（HRB Centre for Primary Care Research）的宝娜·伯恩博士（Dr. Paula Byrne）。在评论这些发现时，宝娜·伯恩博士说:“长期以来，人们一直认为降低胆固醇会降低患心脏病的风险，而他汀类药物有助于实现这一目标。然而，我们的研究表明，实际上，服用他汀类药物的好处是多种多样的，而且可能相当有限。”

研究人员继续建议，这些更新的信息应该通过知情的临床决策及更新的临床指南和政策传达给患者。

上述介绍，仅供参考。欲了解更多信息，敬请注意浏览原文或者相关报道。

Benefits of Taking Statins Called Into Question: Link Between High Cholesterol and Heart Disease “Inconsistent”

关于RCSI简介

RCSI是爱尔兰皇家外科医学院 （Royal College of Surgeons in Ireland）简称，位于爱尔兰共和国首都都柏林，成立于1784年，是所私立医学院。

RCSI医学和健康科学大学(RCSI University of Medicine and Health Sciences)是世界领先的健康和福祉大学。在《2021年泰晤士报高等教育影响排名》(Times Higher Education Impact Rankings 2021)中，它对联合国可持续发展目标3(UN Sustainable Development Goal 3)的贡献在世界上排名第二，它专门专注于推动改善全球人类健康的教育和研究。

RCSI是作为一所国际非盈利大学，在2022年世界大学排名(World University Rankings, 2022)中，它是世界前250所大学之一。RCSI被授予雅典娜·斯旺铜奖（Athena SWAN Bronze Award），以表彰高等教育中的积极性别实践。

Abstract

Importance: The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear.

Objective: To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy.

Data sources: PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021.

Study selection: Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years.

Data extraction and synthesis: Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken.

Main outcomes and measures: Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke.

Findings: Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive.

Conclusions and relevance: The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.