Statin Safety: An Overview and Assessment of the Data—2005
Section snippets
Grading of the Scientific Evidence
The strength of the current scientific evidence supporting the association of statins with specific potential adverse experiences varies with the adverse experience being considered. In some cases, the clinical trial evidence is clear; in other cases, potential adverse experiences are unproved, having only been described in isolated case reports. It therefore is useful to assess the level of scientific evidence of potential safety issues associated with statins. Although no universally accepted
Definitions
Before a drug can be said to be associated with a potential toxicity, it is helpful to have a clear understanding of what defines the adverse experience. Unfortunately, the definitions ascribed to muscle adverse experiences have not always been consistent. In 2002, the American College of Cardiology/American Heart Association/National Heart, Lung, and Blood Institute (ACC/AHA/NHLBI) issued a clinical advisory statement on the use and safety of statins.18 In this advisory statement, myalgia was
Combination Lipid-Altering Drug Therapy
Combination lipid-altering drug treatment is a well-established therapeutic approach for (1) patients with severe hypercholesterolemia, (2) those with more complicated lipid abnormalities, or (3) patients who need aggressive lipid management.19, 67, 68, 69 Clinical trials have shown that the combination of bile acid sequestrants (such as colesevelam) with statins lowers cholesterol levels more than does the same dose of statin monotherapy, without an increased risk of muscle adverse experiences.
Currently Marketed Statin Monotherapy and Clinical Trial Assessment of Muscle Adverse Experiences
With regard to currently marketed statins used as monotherapy at recommended doses, and administered under recommended conditions, no conclusive comparative evidence exists that these statins differ with regard to potential muscle adverse experiences. The exception to this, theoretically, might be in cases where potential drug interactions may occur.6 For example, pravastatin78 and rosuvastatin79 are not significantly metabolized through the cytochrome P450 enzyme (CYP) system. Therefore,
Potential Liver Adverse Experiences
As with muscle, statins have a low risk for potential liver adverse experiences. The levels of evidence for determining whether such an adverse event is associated with statin use are presented in Table 4.27, 34, 77, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115 Severe potential liver adverse experiences have been described in isolated case reports (such as rare reports of possible statin-related cholestatic hepatotoxicity, autoimmune hepatitis, fulminant
Potential Renal Adverse Experiences
Levels of evidence for determining whether potential renal adverse experiences are associated with use of statins are shown in Table 5.7, 18, 21, 22, 23, 131, 132, 133, 134
Proteinuria and hematuria has been described as rare, potential kidney effects associated with all statins (Table 6).21, 135 Although these renal findings had previously been recognized with statin therapy, this issue resurfaced during the vast rosuvastatin development program,131 most likely because (1) rosuvastatin was
Potential Neurologic Adverse Experiences
Levels of evidence supporting that potential neurologic adverse experiences may be related to statin use are listed in Table 7.144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175 Although much is known about the effects of statins on muscle, liver, and even kidney, less is known about potential statin-related neurologic adverse experiences. Neurologic conditions that have been described in
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