July 09, 2013
3 min read

Statins linked to few adverse effects, increased diabetes risk

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Statin use appears to be associated with low risk for adverse effects, but a slight increase in risk for developing diabetes, according to results of a meta-analysis published in Circulation: Cardiovascular Quality and Outcomes.

Simvastatin and pravastatin demonstrated the lowest risk for adverse effects.

Researchers reviewed data from 135 randomized trials that evaluated statins in participants with and without CVD to perform random-effects pairwise and network meta-analyses. The review included 55 two-armed, placebo-controlled trials and 80 two- or multi-armed, active-comparator trials conducted from 1985 to early 2013 comprising 246,955 participants. The trials evaluated seven statins currently on the market. Average follow-up in the studies was 68 weeks.

Overall, statins did not significantly increase risk for myalgia, myopathy, rhabdomyolysis or cancer as compared with control treatment.

Statins as a class were associated with a 9% increased risk for diabetes (OR=1.09; 95% CI, 1.02-1.16) vs. control. Rosuvastatin demonstrated the highest risk (OR=1.16; 95% CI, 1.02-1.31).

“Although the risk of developing diabetes is low, what this risk would amount to over time is simply not known based on the existing evidence,” Huseyin Naci, MHS, lead author and research fellow at Harvard Medical School department of population medicine, said in a press release.

Statins were also linked with significantly higher odds of transaminase elevations (OR=1.51; 95% CI, 1.24-1.84) vs. control. Pravastatin was associated with less risk (OR=0.27; 95% CI, 0.1-0.74) as compared with atorvastatin.

When individual statins were compared in network meta-analyses, simvastatin (OR=0.75; 95% CrI, 0.59-0.95) and pravastatin (OR=0.68; 95% CrI, 0.52-0.91) were associated with less discontinuation due to adverse events than atorvastatin. Pairwise meta-analysis revealed that simvastatin was significantly more tolerable than atorvastatin (OR=0.61; 95% CI, 0.42-0.89) and rosuvastatin (OR=0.49; 95% CI, 0.27-0.88).

Higher doses appeared to impact discontinuation due to adverse effects vs. control, particularly atorvastatin at >20 mg/day and ≤40 mg/day (OR=2.72; 95% CI, 1.46-5.09) and atorvastatin at >40 mg/day (OR=1.69; 95% CI, 1.18-2.44). Higher doses of atorvastatin, fluvastatin, lovastatin and simvastatin were associated with higher odds of transaminase elevations. Simvastatin at >40 mg/day was also linked to increased risk for creatine kinase elevation (OR=4.14; 95% CrI, 1.08-16.24).

“As a class, adverse events associated with statin therapy are not common,” the researchers wrote. “Among individual statins, simvastatin and pravastatin appear safer and more tolerable than other statins.”

Adjustment for age, LDL level and publication year did not explain heterogeneity, according to the researchers.

“Although the benefits of statins clearly outweigh risks at the population level, individualizing such benefits and risks is more difficult,” Naci said. “This brings into sharp focus the importance of identifying the individuals who stand to benefit the most from statin therapy.”

Disclosure: The researchers report no relevant financial disclosures.