Trial designs for statin muscle intolerance

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Purpose of review

This article aims to review the spectrum of statin-associated muscle symptoms (SAMS), the consequences of downtitration of statin therapy on cardiovascular events, the published trials of nonstatin therapy in patients who report SAMS, and to provide a framework for future trials in SAMS patients.

Recent findings

SAMS is reported in 10–25% of patients prescribed statin therapy; however, the few patients enrolled in randomized, double-blind, controlled clinical trials (RCTs) discontinue statin therapy due to adverse events. Several possible reasons for this discrepancy in clinical practice versus RCTs may results from patient selection in clinical trials that excludes patients with characteristics that increase the risk of SAMS, widespread use of higher intensity statins in low-risk populations that evaluated in nearly all RCTs, and perceptions concerning harm of statin therapy. Clinical trials of nonstatin therapy have shown that most patients tolerate statin therapy upon repeat challenge, and thus better tools are needed to more accurately identify SAMS patients and enroll these patients in RCTs of nonstatin therapy.


Clinical trials in patients who report SAMS have shown better tolerability of certain classes of nonstatin therapy. Low rates of recurrent SAMS in double-blind rechallenge have led some to challenge the concept of statin muscle intolerance. However, patients with perceived SAMS downtitrate their statin therapy and suffer more cardiovascular events. A revised paradigm for evaluation of SAMS is proposed.

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