Pharmacologic Safety of Statins as a Class Reaffirmed

A study-level analysis of trials has confirmed that statins as a class are well tolerated, although safety profiles vary from agent to agent.

Researchers at the London School of Economics and Political Science (LSE; United Kingdom), Erasmus Medical Center (Rotterdam, The Netherlands), and other institutions conducted a meta-analysis of 135 randomized controlled trials—55 with a placebo control and 80 with an active comparator—involving 246,955 participants with or without cardiovascular disease (CVD), to examine the comparative tolerability and harms of individual statins. The study initially included trials of atorvastatin, fluvastatin, simvastatin, lovastatin, pravastatin, and rosuvastatin; trials of pitavastatin were added post hoc because the protocol was already being finalized at the time the drug was approved.

The results showed that when individual statins were compared, there were numerous statistically detectable differences, favoring simvastatin and pravastatin. According to dose-level comparisons, individual statins resulted in higher odds of discontinuations with higher doses of atorvastatin and rosuvastatin. Statins as a class resulted in significantly higher odds of diabetes mellitus, compared with control. Similarly, higher doses of atorvasatin, fluvastatin, lovastatin, and simvastatin were associated with higher odds of transaminase elevations, and simvastatin at its highest doses was associated with creatine kinase elevations. The study was published online on July 9, 2013, in Circulation: Cardiovascular Quality and Outcomes.

“Simvastatin and pravastatin appeared to have the best safety profiles, and because of that they should be favored in clinical practice,” concluded lead author Huseyin Naci, MHS, of the LSE, and colleagues. “We acknowledge the complex nature of making prescribing decisions and urge prescribers to consider the findings of this analysis in light of the comparative benefit profiles of individual statins in preventing all-cause mortality, in addition to cardiovascular and cerebrovascular events.”

Statins work by inhibiting HMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body.

Related Links:
London School of Economics and Political Science
Erasmus Medical Center