《柳叶刀》 （The Lancet） 发表的一项系统综述和meta分析发现，在他汀类药物标签上列出的66项副作用中，除已知的可能引发肌肉疼痛和糖尿病这类副作用外，仅肝功能异常、轻微肝脏异常、尿液成分改变和组织肿胀这四种副作用是有证据证实的，且风险极小。

　　他汀类药物在过去的30年中已被使用亿万人次，且已被证明能够降低心脏病、中风发生率和心血管疾病病死率。他汀类药物标签中列出了多种可能的副作用，使得许多人为其安全性担忧，然而能证明这些副作用确实发生的有力证据十分有限。

　　本研究是对他汀类药物已列出的副作用相关证据进行的最全面评估。研究纳入了19项随机对照试验，涵盖了超过120,000受试者，平均试验追踪期为四年半。研究发现，在产品标签上列出的66种副作用中，有62种没有被有力地证明。这其中包括了记忆问题、抑郁、睡眠障碍和导致手脚刺痛的神经损伤。作者特别指出，在他汀类药物的使用时间超过平均随访时间后，可能会出现潜在的副作用。

　　作者表示，研究结果强调了大多数列出的副作用发生的风险极小，且使用他汀类药物对心血管带来的益处显著大于较小概率发生的潜在风险。作者建议，修改他汀类药物标签上当前的副作用清单，以更好地反映相关证据，进而使患者和医生能够做出更为清晰和明智的治疗抉择。 END

　　FundingBritish Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.

　　Declaration of interests

　　CR, LB, JRE, DP, KD, CH, HH, LH, KW, RH, AJR, MJL, BM, JA, RC, and CB are affiliated with the Nuffield Department of Population Health (NDPH) at the University of Oxford, which has an explicit policy of not accepting any personal honoraria payments directly or indirectly from the pharmaceutical and food industries. NDPH only seeks reimbursement to the University of Oxford for the costs of travel and accommodation to participate in scientific meetings (https://www.ndph.ox.ac.uk/about/independence-of-research). Project and departmental grants have been awarded to NDPH by the British Heart Foundation and the UK Medical Research Council which has helped support NDPH staff working on this project. CR reports previously receiving funding to the University of Oxford (but no personal funding) from Merck–Schering-Plough Pharmaceuticals for the SHARP trial of simvastatin–ezetimibe, the UK National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) programme (17/140/02) and holding unpaid roles on the Clinical Data Interchange Standards Consortium as a board member and WHO as a scientific advisor. JRE declares grant funding from Regeneron Pharmaceuticals and AstraZeneca to the University of Oxford (but no personal funding) to support the Mexico City Prospective Study, and Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial. DP reports receiving funding to the University of Oxford (but no personal funding) from Novartis for the ORION 4 trial of inclisiran, Novo Nordisk for the ASCEND PLUS trial of semaglutide, and Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial, and being a committee member for National Institute for Health and Care Excellence Cardiovascular Disease: Risk Assessment and Reduction Including Lipid Modification guideline. ES reports now being an employee of AstraZeneca. CH reports receiving funding to the University of Oxford (but no personal funding) from Novo Nordisk for the ASCEND PLUS trial of semaglutide. AJR reports receiving funding to the University of Oxford (but no personal funding) from the NIHR Oxford Biomedical Research Centre, Boehringer Ingelheim, and Eli Lilly. CPC reports grants or contracts from Amgen, Better Therapeutics, Boehringer-Ingelheim, and Novo Nordisk; salary support from Colorado Prevention Center Clinical Research, which gets research grant support from Amgen, Bayer, Cleerly, Esperion, Lexicon and Silence; consulting fees from Amryt–Chiesi, Amgen, Ascendia, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Genomadix, Lilly, Janssen, Lexicon, Milestone, Novartis, Pfizer, and Rhoshan; and participation on a Data and Safety Monitoring Board (DSMB) or Advisory Board for Areteia, Novo Nordisk, ROMTherapy, and the Veterans Administration. SG reports grants or contracts to his institution from MEXT–JSPS KAKENHI 19H03661, AMED (grant number A368TS and A447TR), and the Nakatani Foundation, consulting fees from Jansen Pharma, Amgen, and Merck Sharp and Dohme, payment or honoraria from Sysmex, and roles as Vice President of The Japanese College of Angiology, Associate Editor for Circulation, and Council Member of the International Society of Thrombosis and Haemostasis. GAH reports funding from Pfizer, Diabetes UK, and NHS England for the CARDS trial. GKH reports being an employee of Novo Nordisk and having stock options in Novo Nordisk. WK reports grants and provision of reagents to their institution from Singulex, Dr Beckmann Pharma, Abbott, and Roche Diagnostics, consulting fees from AstraZeneca, Novartis, Amgen, Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, OMEICOS, Daichii Sankyo, Novo Nordisk, New Amsterdam Pharma, TenSixteen Bio, Genentech, and Esperion, and payment or honoraria from Bristol Myers Squibb, Novartis, Amgen, Berlin-Chemie, Sanofi, and AstraZeneca. MJL reports funding to their institution for clinical trials from Novartis, Regeneron, and Boehringer Ingelheim, funding to their institution for trial methodology research from Regeneron, Moderna, GSK, and Sanofi, funding to their institution for consultancy from GSK, Verve, and Marea, and roles as Adviser, Regulatory Affairs Committee for the European Society of Cardiology and Lead for the Good Clinical Trials Collaborative (funded by Wellcome and the Gates Foundation). BM reports a research grant to the University of Oxford and Queen Mary University of London from UK NIHR HTA (17/140/02) and a research grant to Queen Mary University of London from UK NIHR Barts Biomedical Research Centre, and support for attending meetings or travel from the European Society of Cardiology for attending a round table addressing unmet medical needs in cardiology. CN reports royalties for a textbook from Elsevier of less than US$5000 in the past 3 years, support from the Endocrine Society for travel and registration for lecture and for membership on planning committee in relation to the 2024 and 2025 meetings, and an unpaid roles as Vice President of the Medical Women's International Association and a board member for the Women in Medicine Legacy Foundation. MSS reports research grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis, Marea, Merck, Novartis, Pfizer, Saghmos Therapeutics, and Verve Therapeutics, consulting fees from Amgen, AMPEL BioSolutions, Anthos Therapeutics, AstraZeneca, Beren Therapeutics, Boehringer Ingelheim, CCRN, Dr Reddy's Laboratories, General Medicines, Merck, NATF, Novo Nordisk, and Precision BioSciences, and reports being a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women's Hospital from Abiomed, ARCA Biopharma, Cleerly, Janssen Research and Development, MedImmune, Regeneron Pharmaceuticals, Roche, Softcell Medical, The Medicines Company, and Zora Biosciences. NS reports grants or contracts paid to his institution from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche, consulting fees paid via his institution from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GSK, Hanmi Pharmaceuticals, Menarini-Ricerche, Metsera, Novo Nordisk, Pfizer, and Roche, personal consulting fees from Novartis, and payment or honoraria paid via his institution from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Roche. GGS reports research support to the University of Colorado from AstraZeneca, Sanofi, and Silence Therapeutics and support from The University of Oxford for travel to attend clinical trial steering committee meetings. AMT reports payments for chairing a steering committee related to a survey of the adequacy of lipid management in patients in Australian general practice from Novartis and membership of the Data Monitoring Committee of the ORION-4 study of inclisiran supported by Novartis. HDW reports grant support paid to his institution by Sanofi-Aventis, Regeneron Pharmaceuticals for the ODYSSEY OUTCOMES trial, by American Regent for the HEART–FID study, by DalCor Pharma UK for the GenE Study, by CSL Behring for the AEGIS-II trial, by US National Institutes of Health for the ISCHEMIA and MINT studies, by Esperion Therapeutics for the CLEAR Outcomes study, by Omthera Pharmaceuticals for the STRENGTH trial, by Sanofi Aventis Australia for the SOLIST-WHF and SCORED trials, by Janssen Research and Development for the Librexia AF study and Librexia ACS studies, by Merck Sharp & Dohme (New Zealand) for the MK0616 study; fees from DalCor Pharma UK for serving on the steering committee for the GenE Study, CSL Behring for serving on the steering committee for the AEGIS-II trial, Sanofi Aventis Australia for serving on the steering committee for the SOLIST-WHF and SCORED trials, Esperion Therapeutics for serving on the steering committee for the CLEAR Outcomes study, and Janssen Research and Development for serving on the steering committee for the Librexia AF study and Librexia ACS studies; support from the South Australian Health and Medical Research Institute for attendance at the clinical trial forum (2022 and 2023), the National Health and Medical Research Council (NHMRC) Clinical Trials Centre; being the University of Sydney Chair of the DSMB for the EVIDENCE Study; being on the CSL Behring Advisory Board; and receiving VERVE HF advisory board fees (2024). JA reports an unpaid Independent Data Monitoring Committee role for the WOMAN2 trial. AK reports funding from the NHMRC Australia with an NHMRC Programme grant and Senior Research Fellowship to support all research activities; research grant funding from the Australian Medical Research Future Fund; research grants from Amgen, Abbott, and Viatris; being a DSMB member for the Harvard University and Kowa Pharmaceuticals PROMINENT trial; and drug provisions for research from Viatris. JS reports research grant to his institution from NHMRC Australia, Bristol Myers Squibb, Roche, Bayer, Amgen, and MSD, advisory board fees to his institution from FivepHusion, and being an unpaid Chair of the STAREE DSMB. RC declares grants to the University of Oxford from Merck, Novartis, UK Medical Research Council, British Heart Foundation, Cancer Research UK, AstraZeneca, Wellcome Trust, and Regeneron Pharmaceuticals; a patent for a statin-related myopathy genetic test from Boston Heart Diagnostics for which RC waived any personal reward with any share in royalty and other payments waived in favour of the Nuffield Department of Population Health, University of Oxford; and being Deputy Chair of the not-for-profit clinical trial company PROTAS, Chief Executive of UK Biobank, and Chair of the steering committee of the ORION-4 trial of inclisiran. CB declares support from Boehringer Ingelheim through a grant to the University of Oxford for the EMPA-KIDNEY and EASi-KIDNEY trials, being the Medical Research Council Population Health Research Unit Director from 2019–24, being a co-applicant on a Health Data Research UK Substantive Site award from 2018–23, being an unpaid DSMB or Advisory Board Chair for Merck for a phase 2 trial of factor X1-inhibitor for dialysis patients and for the NIHR HTA to prepare for a kidney care trial, and having unpaid roles in the NIHR HTA as Chair of Aspirin To Target Arterial Events in Chronic Kidney Disease (ATTACK) and Desmopressin for Acute Stroke due to Haemorrhage (DASH). All other authors declare no competing interests.

　　中文翻译仅供参考，所有内容以英文原文为准。

　　DOI: 10.1016/S0140-6736(25)01578-8

　　题图Photo by Peter Dazeley via Getty Images

　　关注柳叶刀服务号，探索更多科研服务！