Portal de Periódicos da CAPES

Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials

2022; Elsevier BV; Volume: 400; Issue: 10355 Linguagem: Inglês

10.1016/s0140-6736(22)01545-8

1474-547X

Christina Reith, Colin Baigent, Lisa Blackwell, Jonathan Emberson, Enti Spata, Kelly Davies, Heather Halls, Lisa Holland, Kate Wilson, Jane Armitage, Charlie Harper, David Preiss, Alistair Roddick, Anthony Keech, John Simes, Rory Collins, Elizabeth H Barnes, Jordan Fulcher, William G. Herrington, Adrienne Kirby, Borislava Mihaylova, Rachel O’Connell, Pierre Amarenco, Philip J. Barter, D. J. Betteridge, Michael A. Blazing, Jackie Bosch, Louise Bowman, Eugene Braunwald, Christopher P. Cannon, Michael Clearfield, Stuart M. Cobbe, Helen M. Colhoun, Björn Dahlöf, Barry R. Davis, James A. de Lemos, John R. Downs, Paul N. Durrington, Bengt Fellström, Ian Ford, Maria Grazia Franzosi, John A. Fuller, Curt D. Furberg, Robert J. Glynn, David Gordon, Antonio M. Gotto, Richard H. Grimm, Ajay Gupta, C Hawkins, G. A. Hitman, Hallvard Holdaas, Alan G. Jardine, J. Wouter Jukema, John J.P. Kastelein, Sharon Kean, John Kjekshus, Genell L. Knatterud, Robert H. Knopp, Wolfgang Köenig, Michael J. Koren, Vera Krane, Martin Landray, John C. LaRosa, Roberto Latini, Eva Lonn, Donata Lucci, Jean MacFadyen, Peter W. Macfarlane, Stephen MacMahon, Aldo P. Maggioni, Roberto Marchioli, Ian C. Marschner, Lemuel A. Moyé, Sabina A. Murphy, Andrew Neil, Enrico Nicolis, Chris J. Packard, Sarah Parish, Terje R. Pedersen, Richard Peto, Marc A. Pfeffer, Neil R Poulter, Sara Pressel, Jeffrey L. Probstfield, Mahboob Rahman, Paul M. Ridker, Michele Robertson, Frank M. Sacks, Naveed Sattar, Roland E. Schmieder, Patrick W. Serruys, Peter Sever, John Shaw, James Shepherd, Lara M. Simpson, Peter Sleight, Luigi Tavazzi, Gianni Tognoni, Andrew Tonkin, Stella Trompet, Christoph Wanner, Hans Wedel, Stephen E. Weis, K.M.A. Welch, Harvey D. White, John Wikstrand, Lars Wilhelmsen, Stephen D. Wiviott, Robin Young, Salim Yusuf, Faı̈ez Zannad, Hiroyuki Arashi, Robert Byington, Robert Clarke, Marcus Flather, Uri Goldbourt, Shinya Goto, Jemma C. Hopewell, Kees Hovingh, Patricia M. Kearney, George D. Kitas, Connie B. Newman, Marc S. Sabatine, Gregory W. Schwartz, Liam Smeeth, Jonathan A. Tobert, George Varigos, Junichi Yamaguchi,

HIV-related health complications and treatments

BackgroundStatin therapy is effective for the prevention of atherosclerotic cardiovascular disease and is widely prescribed, but there are persisting concerns that statin therapy might frequently cause muscle pain or weakness. We aimed to address these through an individual participant data meta-analysis of all recorded adverse muscle events in large, long-term, randomised, double-blind trials of statin therapy.MethodsRandomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration 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. We analysed individual participant data from 19 double-blind trials of statin versus placebo (n=123 940) and four double-blind trials of a more intensive versus a less intensive statin regimen (n=30 724). Standard inverse-variance-weighted meta-analyses of the effects on muscle outcomes were conducted according to a prespecified protocol.FindingsAmong 19 placebo-controlled trials (mean age 63 years [SD 8], with 34 533 [27·9%] women, 59 610 [48·1%] participants with previous vascular disease, and 22 925 [18·5%] participants with diabetes), during a weighted average median follow-up of 4·3 years, 16 835 (27·1%) allocated statin versus 16 446 (26·6%) allocated placebo reported muscle pain or weakness (rate ratio [RR] 1·03; 95% CI 1·01–1·06). During year 1, statin therapy produced a 7% relative increase in muscle pain or weakness (1·07; 1·04–1·10), corresponding to an absolute excess rate of 11 (6–16) events per 1000 person-years, which indicates that only one in 15 ([1·07–1·00]/1·07) of these muscle-related reports by participants allocated to statin therapy were actually due to the statin. After year 1, there was no significant excess in first reports of muscle pain or weakness (0·99; 0·96–1·02). For all years combined, more intensive statin regimens (ie, 40–80 mg atorvastatin or 20–40 mg rosuvastatin once per day) yielded a higher RR than less intensive or moderate-intensity regimens (1·08 [1·04–1·13] vs 1·03 [1·00–1·05]) compared with placebo, and a small excess was present (1·05 [0·99–1·12]) for more intensive regimens after year 1. There was no clear evidence that the RR differed for different statins, or in different clinical circumstances. Statin therapy yielded a small, clinically insignificant increase in median creatine kinase values of approximately 0·02 times the upper limit of normal.InterpretationStatin therapy caused a small excess of mostly mild muscle pain. Most (>90%) of all reports of muscle symptoms by participants allocated statin therapy were not due to the statin. The small risks of muscle symptoms are much lower than the known cardiovascular benefits. There is a need to review the clinical management of muscle symptoms in patients taking a statin.FundingBritish Heart Foundation, Medical Research Council, Australian National Health and Medical Research Council.