The effectiveness of statins in lowering the risk of cardiovascular events in patients with elevated LDL-C is well established now, but muscle-related symptoms, often without increases in serum creatine kinase levels, have limited their use. An interesting study (SE Nissen et al) designed to ameliorate this problem was published in the April 19th issue of JAMA, accompanied by a thoughtful editorial (DD Waters et al).
Patients with uncontrolled LDL-C levels and a history of muscle-related statin intolerance without elevated creatine kinase (n=491) first entered a 24-week crossover trial of atorvastatin and placebo to select out patients who developed symptoms on the statin and not on placebo. That turned out to be 42% (n=209) of the starting group. Those patients and 18 others who had elevated creatine kinase levels entered the next phase of the trial.
In the next phase, the statin-intolerant patients were randomized to receive the cholesterol absorption inhibitor ezetimibe (Zetia), which has been shown to lower LDL-C and (when added to a statin) improve clinical outcomes (Medical Letter, December 8, 2014), or the PCSK9 inhibitor evolocumab (Repatha), which has also been shown to lower LDL-C (Medical Letter, October 12, 2015), but not (yet) to improve clinical outcomes. Evolocumab produced significantly greater reductions in LDL-C levels.
As the editorial points out, that doesn’t totally solve the problem. Besides not knowing how they affect cardiovascular events, PCSK9 inhibitors cost a log or two more than statins, and as we pointed out in The Medical Letter, we don’t know anything about their long-term safety. To be continued.