Statins
Maria G. Tanzi, PharmD
Results of a September 2021 study by Howard and colleagues published in the Journal of the American College of Cardiology show that, in patients with a history of stopping statin therapy due to intolerable adverse effects, a similar amount of adverse effects were observed whether patients were rechallenged with a statin or were taking a placebo.
The research suggests that these adverse effects may be the result of taking the tablets rather than any pharmacologic effects, a phenomenon known as the “nocebo” effect. This occurs when the patient’s negative expectations regarding a treatment cause the treatment to have a more negative effect than it otherwise would have.
“In clinical practice, when patients experience side effects, we suggest stopping the medication for a while and then restarting,” said study author Darrel P. Francis, professor of cardiology at the National Heart and Lung Institute at the Imperial College London. “If the side effects fade away and then return, we think of that as a definite side effect of the medication. Our trial shows this is wrong: the side effects fade away and then return, with equal impressiveness, regardless of whether it is the real medication or just a placebo.”
Study results
This trial, known as SAMSON (Self-Assessment Method for Statin Side-effects Or Nocebo), enrolled 60 patients who had stopped statin therapy with no intention of restarting the medication because of intolerable adverse effects. The most common reasons for stopping statin therapy before enrollment were muscle ache (60%), fatigue or tiredness (15%), and cramps (10%). Patients were randomized to twelve 1-month medication bottles containing 4 months of statin therapy (atorvastatin 20 mg per day); 4 months of placebo tablets; and 4 months of nothing. Daily symptom intensity was monitored on a 1–100 scale, and the “nocebo” ratio was calculated as the ratio of symptoms induced by taking a statin that was also induced by taking a placebo.
A total of 49 patients completed the 12-month protocol, and mean symptom scores were lowest in the no-tablet months (8.0). However, the mean symptoms scores were similar during the statin (16.3) and placebo (15.4) months, with a nocebo ratio of 0.9. Also, neither symptom intensity on starting nor the extent of symptom relief on stopping were different between the statin and placebo groups. At 6 months after the trial, 50% (30) of patients were back on statin therapy.
Clinical implications
Data have shown that more than half of patients stop statins completely within 2 years. This is unfortunate because the benefits of this class of drugs are lost if patients fail to restart therapy.
Patient expectations from statin therapy drive symptoms. When statins are initially prescribed, having conservations with patients before any potential adverse effects occur will help build rapport and confidence in the prescribed treatment.
Pharmacists can reinforce that statin-associated adverse effects such as muscle aches are relatively uncommon. Help patients not only understand potential risks, but also highlight the benefits of statin therapy, including the data supporting their positive effects on reducing heart attacks, strokes, and the risk of dying.
When asked about the broader clinical applicability of the SAMSON study, Francis said, “this means that we need to be much more careful in attributing side effects to medications. We really need manufacturers to provide 0 mg doses of medications so that patients can do this sort of test on themselves. Without 0 mg doses or some other method of having a matching placebo, all this informal experimentation creates and distributes harmful misinformation.”