Tiny (n-of-1) Trials to Overcome Statin-Associated Muscle Pain

Authors:
Elizabeth B. Hearn, PharmD
Stuart T Haines, PharmD, BCPS, BCACP

Reviewers:
Henry Bussey, PharmD
Kathryn (Katie) Kiser, PharmD, BCACP

Citation: Herrett E, Williamson E, Brack K, et al. Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. BMJ 2021;372:n135

The Problem:

Statin therapy slows the progression of atherosclerotic cardiovascular disease (ASCVD), prevents CV events, and saves lives.  Statin therapy is relatively inexpensive and gives us the most cholesterol-lowering bang for our buck.^1,2 Very rarely statins cause severe muscle injury leading to rhabdomyolysis.  Unfortunately, millions of patients experience muscle symptoms like pain, weakness, or stiffness and discontinue statin therapy.^3,4,5  In blinded clinical trials the percentage of patients who experience muscle symptoms is typically in the 3-5% range.  In practice, the percentage of patients who report muscle symptoms is 10-25%.  This disparity between what has been observed in blinded trials and what patients experience when treated with a statin is due, in part, to the nocebo effect — a belief that a medication may cause harm.  Like the placebo effect, the nocebo effect is powerful and real.  But are we too quick to stop these life-saving drugs when muscle symptoms are reported?  Is it possible to sort out when statins are the likely culprit and when something else might be causing muscle pain?³ How many lives could be saved if we routinely used tiny randomized, controlled, blinded trials to determine when statin therapy can be safely continued?³