Abstract P072: Who Becomes Weak on Statins? Effect Modification Exposed in a RCT by Risk Factor Compounding
Background: Some patients develop muscle weakness (MW) on statins but MW has not been affirmed in RCTs. Existing evidence suggests muscle problems may arise more commonly in those who are older, female, have a history of muscle problems, or exercise more. We assessed whether statin effects on MW can be unmasked by attending to effect modification, assessing if pairing of known risk factors (RFs) may amplify and expose MW in subgroups.
Method: In a double blind RCT, 1016 adults (68% men) without DM or CVD were randomized equally to simvastatin 20mg, pravastatin 40mg or placebo for 6 months. MW was rated at baseline (0-10) and as change from baseline (-2 to +2). T-tests of difference in self-rated change in MW compared placebo to each statin arm, examining hypothesized vulnerable subgroups based on a) paired age/sex vulnerability (female + age >65); and paired weakness+exercise vulnerability (baseline weakness rated >0, + regular exercise >5x/week).
Results: Statins vs placebo did not increase MW in the full sample. Trends were not significant in those with individual RFs. Statins significantly increased MW in both risk-factor pairings (Table). In older women, mean MW increase on statins rose as age advanced further, from 0.19 (age >65) to 0.26 (>70), 0.37 (>75), and 1 (>80), while MW on placebo remained unchanged or improved. Statins also increased MW in subjects with any baseline MW (rated >0) who engaged in regular exercise: Effects were larger, but the subgroup smaller.
Discussion: In subgroups suggested by coupling of RFs in existing literature, analysis identifies significantly increased MW with statins vs placebo, providing, to our knowledge, the first RCT evidence of MW on statins. Older women represent an important group in whom MW increased. In those with any baseline MW who exercise regularly (as may be recommended), MW worsened with statins. Findings were consistent across statin randomization arms. This may offer an approach to better unmask adverse effects in RCTs.
- © 2013 by American Heart Association, Inc.