Abstract 16041: Examining the Nocebo Effect of Statins Using Statin Adverse Events Reported in the FDA Adverse Event Reporting System

Abstract

Introduction: Comparison of blinded and nonblinded statin trials have confirmed a nocebo effect, most commonly presenting as subjective muscle and nervous system adverse events (AEs). This study evaluated whether the increase in reported statin AEs over time was associated with the nocebo effect by comparing nocebo-related subjective with objective AEs. Method: A retrospective cohort study was conducted using the FDA Adverse Event Reporting System (FAERS) of statin-associated AEs from 1/2010-12/2019. Statins selected for analysis were atorvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin. Subjective AEs included fatigue, subjective muscular, and nervous system AEs. Objective AEs were hepatic and objective muscular AEs. We compared the number of subjective and objective AEs using Mann-Whitney U, and evaluated the association between AEs and gender and country using linear regression. Quantitative detection of signals was estimated using reporting odds ratio (ROR). Institutional Review Board review was exempt since we used de-identified public data. Results: Of 2,994,487 statin AE reports, more subjective than objective AEs were reported per quarter (mean ± SD: 4777 ± 1375.45 vs 999 ± 276.95; p<0.0001). Simvastatin-associated reports showed signals for higher objective muscular AEs relative to all other statins (ROR 1.53, 95% CI: 1.49-1.58). Females reported more subjective AEs than males per quarter (fatigue 86.98, p=0.035; subjective muscular AE 417.95, p<0.0001; nervous system AE 273.60, p<0.0001), but fewer objective muscular AEs (-125.23, p<0.0001). More subjective AEs and fewer objective AEs were reported in the US relative to other countries per quarter (p<0.0001). Conclusion: This study found that significantly more subjective than objective AEs are reported for statins. Subjective statin AEs, potentially related to the nocebo effect are reported more often by females than by males, and in the US than in other countries.