Statin-associated myalgia among users of generic and brand statins: a potential explanation for the difference in prevalence observed in randomized trials and registries?

INTRODUCTION:
Statins are crucial for primary and secondary prevention of atherosclerosis. Statin-related muscle symptoms (SRMS) limit adherence and effectiveness. While randomized clinical trials (RCTs) show no SRMS difference compared to placebo, real-world data (RWD) indicate the issue is more prevalent. The use of generic statins has increased recently due to their lower cost and perceived comparable efficacy and safety to brand-name versions. We hypothesized that the discrepancies in SRMS incidence between RCTs and RWD may be attributable in part to a higher incidence of SRMS associated with the use of generic statins compared to brand-name statins.

METHOD:
We conducted a retrospective analysis using anonymized data from a national healthcare database of 1,246,890 subjects prescribed simvastatin®, atorvastatin®, pravastatin®, or rosuvastatin® between 1998 and 2023. Subjects were followed for six months after their initial statin prescription. Pharmacy records categorized them as users of either generic or brand-name statins. SRMS incidence was compared between the two groups using multivariable logistic regression, adjusted for age, sex, comorbidities, and concurrent medication use. Persistence, defined as the proportion of patients who purchased the medication for at least five out of six months during the follow-up period, was also compared between the groups.

RESULTS:
The incidence of SRMS was significantly lower among brand-name statin users compared to generic statin users (0.5% Vs. 3%; p <0.001). Multivariate analysis confirmed a higher risk of SRMS in generic formulations than in brand statins (OR: 3.77, 95% CI: 3.56–3.99; p<0.001). Persistence rates were 42% for brand-name statins versus 39% for generic statins (p<0.001).

CONCLUSION:
In a large national cohort, generic statins were linked to higher SRMS rates and lower persistence than brand-name statins. This may explain the lower SRMS rates seen in RCTs compared to RWD. The potential benefit of switching patients with SRMS to brand-name statins should be investigated.