Assessment of adverse effects attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials

作者：Christina Reith, Lisa Blackwell, Jonathan R Emberson, David Preiss, Enti Spata, Kelly Davies, Heather Halls, Charlie Harper, Lisa Holland, Kate Wilson, Robert Humphrey, Alistair Roddick, Christopher P Cannon, Barry R. Davis, Paul N Durrington, Shinya Goto, Graham A Hitman, G Kees Hovingh, Wolfgang Koenig, Vera Krane, Martin J Landray, Borislava Mihaylova, Connie B. Newman, Jeffrey L Probstfield, Marc S Sabatine, Naveed Sattar, Gregory G. Schwartz, Andrew M Tonkin, Harvey D White, Jane Armitage, Anthony Keech, John Simes, Rory Collins, Colin Baigent, Elizabeth Barnes, Jordan Fulcher, William G. Herrington, Adrienne Kirby, Rachel O'Connell, Pierre Amarenco, Hiroyuki Arashi, Philip Barter, D John Betteridge, Michael A. Blazing, Gerard J Blauw, Marc Bonaca, Jackie Bosch, Louise Bowman, Eugene Braunwald, Richard Bulbulia, Robert P. Byington, Robert Clarke, Michael Clearfield, Stuart Cobbe, Helen M Colhoun, Björn Dahlöf, James de Lemos, John R. Downs, Bengt Fellström, Lawrence Fine, Marcus Flather, Ian Ford, Maria Grazia Franzosi, John Fuller, Curt Furberg, Robert J Glynn, U. Goldbourt, David Gordon, Jr Antonio Gotto, Richard Grimm, Ajay Gupta, C Morton Hawkins, Richard Haynes, Hallvard Holdaas, Jemma Hopewell, Alan G. Jardine, J. Wouter Jukema, John JP Kastelein, Sharon Kean, Patricia Kearney, George D Kitas, John Kjekshus, Genell Knatterud, Robert H. Knopp, John Kjekshus, Michael Koren, John C. LaRosa, Roberto Adriano Latini, Eva Lonn, Donata Lucci, Jean MacFadyen, Peter Macfarlane, Stephen MacMahon, Aldo Maggioni, Roberto Marchioli, Ian C. Marschner, Lemuel A. Moyé, Heather Murray, Sabina A Murphy, Andrew Neil, Enrico Nicolis, Chris Packard, Sarah Parish, Terje R. Pedersen, R. Peto, Marc A. Pfeffer, Neil Poulter, Sara Pressel, Mahboob Rahman, Paul M Ridker, Michele Robertson, Frank Sacks, Roland Schmieder, Patrick W Serruys, Peter Sever, John Shaw, James Shepherd, Lara M. Simpson, Peter Sleight, Liam Smeeth, Luigi Tavazzi, Jonathan A. Tobert, Gianni Tognoni, Stella Trompet, J VARIGOS, Christoph Wanner, H. Wedel, Stephen Weis, K Michael Welch, John Wikstrand, Lars Wilhelmsen, Stephen Wiviott, Junichi Yamaguchi, Robin Young, Salim P. Yusuf, Faïez Zannad · 发表于：The Lancet · 年份：2026 · DOI：10.1016/s0140-6736(25)01578-8 · 被引用次数：28 · 研究领域：Lipoproteins and Cardiovascular Health、Cancer, Lipids, and Metabolism、Pharmacovigilance and Adverse Drug Reactions

BACKGROUND: Statin product labels (eg, Summaries of Product Characteristics [SmPCs]) list certain adverse outcomes as potential treatment-related effects based mainly on non-randomised and non-blinded studies, which might be subject to bias. We aimed to assess the evidence for such undesirable effects more reliably through a meta-analysis of individual participant data from large double-blind trials of statin therapy. METHODS: In this meta-analysis of individual participant-level data from double-blind randomised controlled trials, we generated a list of all undesirable effect terms listed in statin SmPCs by searching an electronic medicines compendium for five statins (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin). Randomised trials were eligible for meta-analysis of these effects if they involved at least 1000 participants, had a scheduled treatment period of at least 2 years, and involved a double-blind comparison of statin versus placebo or of a more intensive versus a less intensive statin regimen. Event rate ratios (RRs) and 95% CIs were calculated with statistical significance assessed after controlling the false discovery rate (FDR) at 5%. FINDINGS: 19 trials compared statin versus placebo (123 940 participants, median follow-up 4·5 years [IQR 3·1-5·4]). In addition to previously reported effects on muscle outcomes and diabetes, only four of 66 further undesirable outcomes that had been attributed to statins were FDR significant: abnormal live...