HEPATIC EFFECTS ARE RARE
Historically, statins have been linked to potential hepatotoxicity, with case reports of serum transaminase elevation, cholestasis, hepatitis, and acute liver failure. It is now recognized that hepatic AEs are rare and that statins are not associated with a risk for acute or chronic liver failure.1,11 In patients with coronary heart disease, the incidence of hepatotoxicity with statin use is reported to be less than 1.5% over the course of five years and appears to be dose-dependent.1
In 2012, the FDA revised the labeling for most statins, relaxing its earlier recommendations for monitoring of liver function, clarifying the risk for myopathy, and providing additional information about drug interactions.13
Checking transaminase levels before initiating therapy is recommended by both the ACC/AHA and the FDA.1,13 Routine monitoring is not necessary, the ACC/AHA guideline states, because RCTs have found little evidence of ALT/AST elevation.1 But here, too, evidence varies. An older meta-analysis (13 trials and nearly 50,000 participants) concluded that as a class, statins have no greater risk for transaminase elevations than placebo.22 But the 135-RCT meta-analysis4 found otherwise: Statins did increase the risk for transaminase elevation (odds ratio [OR], 1.51) compared with placebo, with differences associated with particular drugs and higher doses associated with more clinically significant elevations.4 It is important to note, however, that there was significant heterogeneity among the studies and no consistent definition of clinical significance.
The bottom line: Statins have been shown in multiple prospective studies to be safe for patients with chronic liver disease.22,23
STATIN USE AND DIABETES: IS THERE A LINK?
Recent studies have found an increased risk for new-onset type 2 diabetes in statin users, with a greater risk associated with higher-potency statins, including rosuvastatin and atorvastatin.4,24 Although the exact mechanism is not known, statins may modify insulin signaling in peripheral tissues or directly impair insulin secretion.
The ACC/AHA guideline reports an excess rate of diabetes of one per 1,000 patient-years for moderate-intensity therapy and three per 1,000 patient-years for high-intensity therapy.1 The 2013 meta-analysis found that the elevated risk for diabetes was relatively small (OR, 1.09).4 No difference among various statins was found.
In another meta-analysis—this one encompassing 17 RCTs and more than 110,000 patients—no statistically significant difference in the incidence of new-onset diabetes was seen based on either the specific statin being taken or the intensity of therapy (high vs moderate).24
The bottom line: Clinicians should monitor patients taking statins for signs and symptoms of hyperglycemia.
STATINS MAY BE RENOPROTECTIVE
Statin use has been found to be associated with an increased risk for tubular proteinuria—an effect that is both dose- and potency-dependent.25 Nonetheless, it has been suggested that statins may be a rare example of a drug class that is renoprotective in the long term, despite having an increased rate of proteinuria in the short term.25
The evidence? In prospective studies, statin therapy has been shown to slow the progression of kidney disease in diverse patient populations, including renal transplant recipients and those with chronic kidney disease (CKD).26,27
The Kidney Expert Panel of the National Lipid Association (NLA) has concluded that statins do not appear to cause significant proteinuria or acute kidney injury. The panel does not recommend routine monitoring for proteinuria or kidney function in statin users unless otherwise indicated but does recommend a lower dose for patients with CKD.28
The bottom line: Kidney Disease Improving Global Outcomes guidelines recommend that patients who have CKD, but are not on dialysis, be treated with statin therapy. Statins are contraindicated for patients on dialysis, as clinical trials have failed to show significant cardiovascular benefit.29
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