Safety and efficacy of statins

Abstract

Rory Collins and colleagues1Collins R Reith C Emberson J et al.Interpretation of the evidence for the efficacy and safety of statin therapy.Lancet. 2016; 388: 2532-2561Summary Full Text Full Text PDF PubMed Scopus (1122) Google Scholar conclude that statins do not cause muscle complaints without marked increases in concentrations of creatine kinase because such symptoms are not observed in randomised controlled clinical trials (RCTs). They suggest that such symptoms are imagined or misattributed by patients who have been warned about possible muscle complaints. The STOMP trial2Parker BA Capizzi JA Grimaldi AS et al.Effect of statins on skeletal muscle function.Circulation. 2013; 127: 96-103Crossref PubMed Scopus (347) Google Scholar was designed to examine muscle complaints in patients assigned to atorvastatin 80 mg daily or placebo. Participants were queried bi-weekly about muscle symptoms. An outcome of myalgia required resolution of pain with treatment cessation and reappearance on re-challenge. 19 of 203 (9·4%) patients on atorvastatin and 10 of 217 (4·6%) patients on placebo developed myalgia (p=0·054), suggesting that 4·8% of patients develop myalgia because of statin use.2Parker BA Capizzi JA Grimaldi AS et al.Effect of statins on skeletal muscle function.Circulation. 2013; 127: 96-103Crossref PubMed Scopus (347) Google Scholar This is a remarkable figure given that subjects were young (mean age= 44·1 years), totally healthy, and treated for only 6 months. As pre-planned, we excluded 29 statin and 19 placebo patients who discontinued participation because of time, relocation, or non-muscle symptoms. Collins and colleagues1Collins R Reith C Emberson J et al.Interpretation of the evidence for the efficacy and safety of statin therapy.Lancet. 2016; 388: 2532-2561Summary Full Text Full Text PDF PubMed Scopus (1122) Google Scholar reanalysed our data, including these subjects—yielding myalgia rates of 8·2% for patients on atorvastatin versus 4·2% on placebo (p=0·08)—which is a questionable approach, since we sought to determine symptoms in subjects actually taking the drug. Our p value exceeds the magical 0·05 of significance, but it is very close to this statistical threshold. How could RCTs miss mild symptoms? By not asking. Only one of 44 statin RCTs involved querying participants specifically about muscle symptoms.3Ganga HV Slim J Thompson PD A sytematic review of statin-induced muscle problems in clinical trials.Am Heart J. 2014; 168: 6-15Summary Full Text Full Text PDF PubMed Scopus (180) Google Scholar Perhaps Collins and colleagues should perform a larger STOMP-like RCT to make sure they are right before concluding that statin myalgia does not exist. BT reports grants from Regeneron Pharmaceuticals during the conduct of the study. PDT reports grants and personal fees from Regeneron, grants and personal fees from Sanofi, personal fees from Amgen, grants and personal fees from Amarin, personal fees from Merck, and grants from Genomas, Esperion, and Pfizer, outside the submitted work, and owns stock in the following companies, which are involved in drug manufacture and sales or make medical devices: Abbvie, Abbott Labs, CVS, General Electric, Johnson & Johnson, Medtronic, and Sarepta. Interpretation of the evidence for the efficacy and safety of statin therapyThis Review is intended to help clinicians, patients, and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomised controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment. Full-Text PDF Safety and efficacy of statins – Authors' replyThe comments by Simon Dimmitt and colleagues have already been addressed in a response to a previous letter from them.1 In particular, lowering LDL cholesterol more intensively with higher-dose statin therapy has been shown to produce larger reductions in vascular events than with smaller LDL reductions. With respect to the suggestion that adverse effects contribute to more than half of patients discontinuing statin therapy, results from randomised masked trials have shown that patients are no more likely to discontinue statin therapy than placebo; that is, Dimmitt and colleagues confuse attribution with causation (as did John Abramson and colleagues2,3). Full-Text PDF