A Comprehensive Description of Muscle Symptoms Associated with Lipid-Lowering Drugs
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
A spectrum of disease from myalgia to rhabdomyolysis exists as classic side-effect of lipid-lowering treatment (LLT). While myopathy has generated considerable interest, mild musculo-skeletal symptoms are poorly assessed.
Objective: To report on the muscular side-effects of LLT with a particular focus on the overlooked milder ones.
Methods: Hyperlipidemic patients under LLT and complaining of muscle symptoms were asked to complete a self administered questionnaire. Among the 815 adult hyperlipidemic patients under LLT and referred to the cardiovascular prevention unit of La Pitie Hospital, 165 patients answered that they experienced, or had experienced, muscle symptoms which they attributed to the LLT. One hundred and thirty three of these completed and returned a self-administered questionnaire.
Results: A clear chronological link between symptoms and the LLT was revealed, either because they appeared soon after drug initiation or because of an improvement after drug withdrawal.
While cramps and stiffness were the most frequent symptoms, tendonitis-associated pain was surprisingly common, reported in almost half the cases. Pain was often diffuse with a focus on a given location, mainly lower limbs. 39% of patients had used analgesics for pain relief. Unpredictably, a majority of patients reported pain during rest and the lying position. In a number of cases, a family history of pain under LLT was revealed.
Conclusion: The impact of these mild symptoms on daily activities might not be negligible in a subset of patients. The role and importance of a genetic background predisposing to low-grade myopathy deserves further investigation.
Supplementary Material (0)
- Hunninghake D. LDL-cholesterol as a determinant of coronary heart disease. Clin Ther 1990; 12: 370-375.
- LaRosa JC, Hunninghake D, Bush D, et al. The cholesterol facts. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. A joint statement by the American Heart Association and the National Heart, Lung, and Blood Institute. The Task Force on Cholesterol Issues, American Heart Association. Circulation 1990; 81: 1721-1733.
- Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease. The Framingham Study. Ann Epidemiol 1992; 2: 23-28.
- Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. Am J Cardiol 1994; 74: 667-673.
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-1389.
- Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 1301-1307.
- Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001-1009.
- Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998; 339: 1349-1357.
- Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of AFCAPS/ TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279: 1615-1622.
- Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987; 317: 1237-1245.
- Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341: 410-418.
- Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dl) plus two additional atherosclerotic risk factors. The Pravastatin Multinational Study Group for Cardiac Risk Patients. Am J Cardiol 1993; 72: 1031-1037.
- Nawrocki JW, Weiss SR, Davidson MH, et al. Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a newHMG-CoAreductase inhibitor. Arterioscler Thromb Vasc Biol 1995; 15: 678-682.
- Bertolini S, Bon GB, Campbell LM, et al. Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia. Atherosclerosis 1997; 130: 191-197.
- Bakker-Arkema RG, NawrockiJW, Black DM. Safety profile of atorvastatin-treated patients with low LDL-cholesterol levels. Atherosclerosis 2000; 149: 123-129.
- Steinhagen-Thiessen E. Comparative efficacy and tolerability of 5 and 10 mg simvastatin and 10 mg pravastatin in moderate primary hypercholesterolemia. Simvastatin Pravastatin European Study Group. Cardiology 1994; 85: 244-254.
- Omar MA, Wilson JP, Cox TS. Rhabdomyolysis and HMGCoA reductase inhibitors. Ann Pharmacother 2001; 35: 1096-1107.
- Davidson MH, Stein EA, Dujovne CA, et al. The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day. Am J Cardiol 1997; 79: 38-42.
- Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002; 346: 539-540.
- Bolego C, Baetta R, Bellosta S, Corsini A, Paoletti R. Safety considerations for statins. Curr Opin Lipidol 2002; 13: 637-644.
- Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003; 289: 1681-1690.
- Thompson PD, Nugent AM, Herbert PN. Increases in creatine kinase after exercise in patients treated with HMG Co-A reductase inhibitors. JAMA 1990; 264: 2992.
- Ucar M, Mjorndal T, Dahlqvist R. HMG-CoA reductase inhibitors and myotoxicity. Drug Saf 2000; 22: 441-457.
- Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C.ACC/AHA/NHLBIclinical advisory on the use and safety of statins. Circulation 2002; 106: 1024-1028.
- Franc S, Bruckert E, Giral P, Turpin G. [Rhabdomyolysis in patients with preexisting myopathy, treated with antilipemic agents]. Presse Med 1997; 26: 1855-1858.
- Lambrecht LJ, Malini PL. Efficacy and tolerability of simvastatin 20mgvs pravastatin 20mgin patients with primary hypercholesterolemia. European Study Group. Acta Cardiol 1993; 48: 541-554.
- Dart A, Jerums G, Nicholson G, et al. A multicenter, doubleblind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia. Am J Cardiol 1997; 80: 39-44.
- Jokubaitis LA. Updated clinical safety experience with fluvastatin. Am J Cardiol 1994; 73: 18D-24D.
- Dujovne CA, Chremos AN, Pool JL, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin. Am J Med 1991; 91: 25S-30S.
- Chazerain P, Hayem G, Hamza S, Best C, Ziza JM. Four cases of tendinopathy in patients on statin therapy. Joint Bone Spine 2001; 68: 430-433.
- Mulder AB, van Lijf HJ, Bon MA, et al. Association of polymorphism in the cytochrome CYP2D6 and the effi-cacy and tolerability of simvastatin. Clin Pharmacol Ther 2001; 70: 546-551.
- Chong PH, Seeger JD, Franklin C. Clinically relevant differences between the statins: Implications for therapeutic selection. AmJMed 2001; 111: 390-400.
- Benghozi R, Bortolini M, Jia Y, Isaacsohn JL, Troendle AJ, Gonasun L. Frequency of creatine kinase elevation during treatment with fluvastatin. Am J Cardiol 2002; 89: 231-233.
- Sinzinger H, Lupattelli G, Chehne F, Oguogho A, Furberg CD. ACE-inhibitor rather than HMG-co-enzyme-A-reductase inhibits causative for CK-elevation? A case report. Atherosclerosis 2000; 148: 205.
- Imai Y, Watanabe N, Hashimoto J, Muscle cramps and elevated serum creatine phosphokinase levels induced by ?-adrenoceptor blockers. Eur J Clin Pharmacol 1995; 48: 29-34.
- Lane RJM, Mastaglia FL. Drug induced myopathies in man. Lancet 1978; II(8089): 562-566.
- Sinzinger H, Schmid P, O'Grady J. Two different types of exercise-induced muscle pain without myopathy and CKelevation during HMG-Co-enzyme-A-reductase inhibitor treatment. Atherosclerosis 1999; 143: 459-460.
- Phillips PS, Haas RH, Bannykh S, et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med 2002; 137: 581-585.
- Pierce LR, Wysowski DK, Gross TP. Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. JAMA 1990; 264: 71-75.
- Gotto AM Jr. Safety and statin therapy: Reconsidering the risks and benefits. Arch Intern Med. 2003; 163: 657-659.
- Sinzinger H, Lupattelli G, Chehne F, Oguogho A, Furberg CD. Isoprostane 8-epi-PGF2alpha is frequently increased in patients with muscle pain and/or CK-elevation after HMGCo-enzyme-A-reductase inhibitor therapy. J Clin Pharm Ther 2001; 26: 303-310.
- Smith CC, Bernstein LI, Davis RB, Rind DM, Shmerling RH. Screening for statin-related toxicity: The yield of transaminase and creatine kinase measurements in a primary care sitting. Arch Intern Med 2003; 163: 688-692.
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet 2002; 360(9326): 7-22.
- Dietz BL, Oberg KC. Judicious evaluation of adverse drug reactions: Inaccurate assessment of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor-induced muscle injury. Pharmacotherapy 1999; 19: 232-235.
- Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al.Amethod for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-245.
About this Article
- A Comprehensive Description of Muscle Symptoms Associated with Lipid-Lowering Drugs
Cardiovascular Drugs and Therapy
Volume 17, Issue 5-6 , pp 459-465
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers
- Additional Links
- HMG-CoA-reductase inhibitors
- muscle side-effects
- Industry Sectors