What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice

European Journal of Preventive Cardiology

Volumn 21, Issue 4, 2014, Pages 464-474

  Finegold, Judith A ^a   Manisty, Charlotte H ^a   Goldacre, Ben ^b   Barron, Anthony J ^a   Francis, Darrel P ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^b LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

Author keywords

Adverse events; meta analysis; side effects; statins

Indexed keywords

AMINOTRANSFERASE; ATORVASTATIN; FLUINDOSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MEVINOLIN; PLACEBO; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; BIOLOGICAL MARKER;

AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; CLINICAL TRIAL; DEATH; DRUG EFFICACY; FATIGUE; HUMAN; MYOPATHY; PRIMARY PREVENTION; PRIORITY JOURNAL; RHABDOMYOLYSIS; SECONDARY PREVENTION; SIDE EFFECT; SYSTEMATIC REVIEW; BLOOD; CHEMICALLY INDUCED; DIABETES MELLITUS; DOSE RESPONSE; DRUG EFFECTS; ENZYMOLOGY; LIVER; META ANALYSIS; MUSCLE DISEASE; PLACEBO EFFECT; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK ASSESSMENT; RISK FACTOR; TREATMENT OUTCOME;

BIOLOGICAL MARKERS; DIABETES MELLITUS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LIVER; MUSCULAR DISEASES; PLACEBO EFFECT; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK ASSESSMENT; RISK FACTORS; TREATMENT OUTCOME;

EID: 84896480475     PISSN: 20474873     EISSN: None     Source Type: Journal    
DOI: 10.1177/2047487314525531     Document Type: Article

References (35)

1. Nichols GA, Koro CE. Does statin therapy initiation increase the risk for myopathy? An observational study of 32,225 diabetic and nondiabetic patients. Clin Ther. 2007 ; 29: 1761-1770
2. Bruckert E, Hayem G, Dejager S, et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients - the PRIMO study. Cardiovasc Drugs Ther. 2005 ; 19: 403-414
3. Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010 ; 340: c2197 - c2197
4. Smeeth L, Douglas I, Hall AJ, et al. Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Br J Clin Pharmacol. 2009 ; 67: 99-109
5. Kashani A, Phillips CO, Foody JM, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. 2006 ; 114: 2788-2797
6. Taylor F, Ward K, Moore TH, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011 ; 1: CD004816 - CD004816
7. Silva MA, Swanson AC, Gandhi PJ, et al. Statin related adverse events: a meta-analysis. Clin Ther. 2006 ; 28: 26-35
8. Barsky AJ, Saintfort R, Rogers MP, et al. Nonspecific Medication Side Effects and the Nocebo Phenomenon. JAMA. 2002 ; 287: 622-627
9. Colloca L, Finniss D. Nocebo effects, patient-clinician communication, and therapeutic outcomes. JAMA. 2012 ; 307: 567-568
10. Barron AJ, Zaman N, Cole GD, et al. Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control. Int J Cardiol. 2013 ; 168: 3572-3579
11. Thavendiranathan P, Bagai A, Brookhart MA, et al. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 ; 166: 2307-2313
12. Baigent C, Keech A, Kearney PM, et al. CTT Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005 ; 366: 1267-1278
13. Ray KK, Seshasai SR, Erqou S, et al. Statins and all-cause mortality in high-risk primary prevention. Arch Intern Med. 2010 ; 170: 1024-1031
14. Naci H, Brugts JJ, Fleurence R, et al. Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality. Eur J Prev Cardiol. 2013 ; 20: 641-657
15. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010 ; 376: 1670-1681
16. Stegmayr BG, Brännström M, Bucht S, et al. Nediat Study Group. Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study. Scand J Urol Nephrol. 2005 ; 39: 489-497
17. Holdaas H, Fellström B, Jardine AG, et al. ALERT Study Investigators. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet. 2003 ; 361: 2024-2031
18. Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med. 1995 ; 333: 621-627
19. O'Rourke B, Barbir M, Mitchell AG, et al. Efficacy and safety of fluvastatin therapy for hypercholesterolemia after heart transplantation. Int J Cardiol. 2004 ; 94: 235-240
20. MRC/ BHF Heart Protection Study Collaborative Group, Armitage J, Bowman L, Collins R, et al. Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebo-controlled trial in 20,536 high-risk people. BMC Clin Pharmacol. 2009 ; 9: 6-6
21. Carter AA, Gomes T, Camacho X, et al. Risk of incident diabetes among patients treated with statins: population based study. BMJ. 2013 ; 346: f2610 - f2610
22. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011 ; 305: 2556-2564
23. Waters DD, Ho JE, DeMicco DA, et al. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011 ; 57: 1535-1545
24. Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012 ; 380: 565-571
25. Calderon RM, Cubeddu LX, Goldberg RB, et al. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Lancet. 2010 ; 85: 349-356
26. Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs-do rates reported in clinical trials reflect rates in primary care settings?. N Engl J Med. 1995 ; 332: 1125-1131
27. Rothwell PM. External validity of randomised controlled trials: "To whom do the results of this trial apply"?. Lancet. 2005 ; 365: 82-93
28. Galtier F, Mura T, Raynaud de Mauverger E, et al. Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers. Toxicol Appl Pharmacol. 2012 ; 263: 281-286
29. Päivä H, Thelen KM, Van Coster R, et al. High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clin Pharmacol Ther. 2005 ; 78: 60-68
30. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 ; 350: 1495-1504
31. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study. JAMA. 2005 ; 294: 2437-2445
32. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction. Lancet. 2010 ; 376: 1658-1669
33. de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004 ; 292: 1307-1316
34. LaRosa JC, Grundy SM, Waters DD, et al. TNT Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005 ; 352: 1425-1435
35. Rosenzweig P, Brohier S, Zipfel A. The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Clin Pharmacol Ther. 1993 ; 54: 578-583