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      Combination lipid-lowering therapy with statins: safety issues in the postcerivastatin era.

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      Expert opinion on drug safety
      Informa Healthcare

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          Abstract

          Combination lipid-altering regimens represent an emerging clinical paradigm to meet increasingly stringent consensus lipoprotein targets for coronary prevention. This practice, together with escalating prevalences of coronary artery disease in certain ageing (western industrial) populations, polypharmacy in the elderly and the recent voluntary market withdrawal of cerivastatin, warrants a re-examination of the safety profiles of 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (i.e., statins). These agents are exceedingly well-tolerated in the vast majority of patients, very infrequently precipitating musculoskeletal symptoms and/or signs. Statins vary in their pharmacological profiles, leading to distinct levels of systemic exposure and capacities to penetrate skeletal myocytes. Pharmacokinetic interactions with certain agents increase the likelihood of statin-induced myopathy and, in exceedingly rare instances, potentially fatal rhabdomyolysis with myoglobinuria and renal failure. As with other medical decisions, the anticipated benefits of long-term statin therapy, with or without other lipid-altering agents, need to be weighed against the prospects of clinically significant drug interactions. In clinical trials and postmarketing surveillance, the two statins that are not metabolised by the cytochrome P450 3A4 system (fluvastatin and pravastatin) have exhibited very low propensities to elicit myopathy when combined with other agents. These agents should be considered initially when contemplating combination lipid-lowering regimens for coronary prevention.

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          Author and article information

          Journal
          Expert Opin Drug Saf
          Expert opinion on drug safety
          Informa Healthcare
          1474-0338
          1474-0338
          May 2003
          : 2
          : 3
          Affiliations
          [1 ] Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303, USA. tjaco02@emory.edu
          Article
          10.1517/14740338.2.3.269
          12904106
          88764aa5-14a8-4d74-afcc-51c5abf3e95f
          History

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