CardioExchange Archive

CardioExchange’s Harlan Krumholz asked Huseyin Naci and Jasper Brugts about their recent  systematic review of clinical trials with statins published in Circulation: Cardiovascular Quality and Outcomes.

Krumholz: There has been so much recent discussion about the safety of statins. What does your study add to the discussion?

Naci & Brugts: Our study, which is the largest meta-analysis on the side effects of statins to date, confirms the findings of previous meta-analyses in four ways:

1. Statins do not result in an increased risk of developing cancer.
2. Their use is associated with a slight increase in the risk of new onset diabetes.
3. Statins are associated with an increased risk of hepatic transaminase elevations.
4. More intensive statin therapy is associated with greater risk of harm and less favorable tolerability as compared to lower doses.

We also show that there are differences among individual statins, with simvastatin and pravastatin likely to be ranked superior to their alternatives in terms of their safety profile. In particular:

1. The odds of discontinuing the trials because of adverse events were higher among people receiving atorvastatin as compared to those receiving pravastatin and simvastatin.
2. The odds of experiencing liver enzyme irregularities were higher with atorvastatin as compared to pravastatin and simvastatin.
3. Although this finding was associated with great uncertainty, the odds of experiencing creatine kinase elevations with fluvastatin were higher than with other statins (except for lovastatin).

Recent controversy focused on the association of statin use and new-onset diabetes. Our study confirms that there is a 9% increase in the odds of developing diabetes when using statins. However, over 250 individuals need to be treated with statins for one case of diabetes to develop. As previous meta-analyses (including our own: Brugts JJ et al. BMJ 2009 and Naci H et al. Eur J Prev Cardiol 2013) have quantified, cardiovascular benefits of statin therapy greatly outweigh this small increase in diabetes risk in individuals with, or at high risk of developing, coronary heart disease.

Krumholz: What do you think doctors should tell patients about statins? What is the essential information they need to know?

Naci & Brugts: As with any drug, statins have both benefits and harms. We show that harmful side effects of statins are not common, and they are greatly outweighed by their benefits. In the case of transaminase and creatine kinase elevations, side effects are primarily asymptomatic and reversible once therapy is discontinued or switched. Our study provides much-needed evidence on the comparative harm profiles of individual statins, allowing doctors to make more informed decisions when choosing among statins.

In secondary prevention, cardiovascular benefits of statins are indisputable. For those concerned about the more modest benefits associated with statin use in primary prevention, cardiovascular benefits still greatly outweigh the small increase in diabetes risk. For individuals who are at very low risk of developing coronary heart disease, doctors may need to consider the following issues when having candid conversations with their patients:

1. Individuals who are at very low risk of developing coronary heart disease may greatly benefit from physical activity and diet.
2. Paradoxically, a recent study showed that statins might actually decrease the fitness benefits of exercise.
3. Based on the existing clinical trials, we simply do not know what the added diabetes risk associated with statin therapy would amount to in the long term.