DO STATINS CAUSE MUSCLE PAIN?
December 3, 2021 - Do statins cause muscle pain? The short answer is no, they don't. Before delving into this sensitive topic, it's important to distinguish between muscle pain and muscle toxicity. Muscle pain is just that - achy muscles. Muscles can become achy from overuse, physical injury, or as a response to systemic inflammation (e.g. flu). Muscle toxicity, on the other hand, occurs when muscle cells begin to break down and necrose. In its most severe form, muscle toxicity can lead to rhabdomyolysis, a condition where myoglobin released from disintegrating muscles damages the kidneys.
In rare cases, statins can cause muscle toxicity. A review by the AHA found that statins cause muscle toxicity in less than 0.1% of patients. The same paper concluded that the risk of statin-induced rhabdomyolysis was around 0.01%.
So what about muscle pain? Most patients prescribed statins are warned that they may cause muscle pain, and for the small number of patients (<0.1%) who develop muscle toxicity, muscle pain will occur. As far as the other 99.9%+ of patients without muscle toxicity, the evidence does not support the existence of statin-induced muscle pain; this is surprising to a lot of people given the widely held belief that muscle pain is a common side effect of statins. A review of statin trials that encompassed 74,102 patients found that the incidence of muscle pain with statins was no different than placebo. [PMID 17159064] Taking things a step further, a handful of studies have randomized patients who reported statin-induced muscle pain to another statin or placebo. In one study, 200 statin-intolerant patients were assigned to a random sequence of six double-blinded treatment periods (two months each) of atorvastatin 20 mg daily or placebo. At the end of the trial, there was no significant difference in muscle symptom scores between the atorvastatin and placebo periods. [PMID 33627334] In another study, 60 patients who had quit taking statins for any reason (60% for muscle aches) were given twelve 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. The participants took the pills in random order over the course of a year. At the end of the trial, there was no significant difference in statin symptom scores between the atorvastatin and placebo months. In the empty bottle months, scores were much lower. [PMID 34531021]
Muscle pain from statins appears to be related to the "nocebo effect," a phenomenon where negative expectations increase the occurrence of a side effect beyond its true incidence. In practice, it is difficult to get patients who have quit statins to restart them. Even when presented with substantial evidence to the contrary, patients have a hard time accepting the fact that statins don't give them pain. This all goes to show that in one's mind, perception is often stronger than reality.