Propranolol and the risk of hospitalized myopathy: translating chemical genomics findings into population-level hypotheses.

BACKGROUND: A recent large-scale, chemical screening study raised the hypothesis that propranolol may increase the risk of myopathy. We tested this hypothesis in a large population to assess whether (1) propranolol use is associated with an increased risk of myopathy and (2) the concurrent use of propranolol with a statin may further increase risk of myopathy.
METHODS: New users of propranolol and other beta-blockers (BBs) aged >/=65 were identified using data from Medicare and drug benefit programs in 2 states (1994-2005). The primary end point studied was hospitalization for myopathy or rhabdomyolysis. We used stratified Cox proportional hazards regression to estimate the multivariate-adjusted effect of propranolol compared to other BBs and controlled for demographic variables, risk factors for myopathy, other comorbidities, and health service use measures. We also assessed whether co-use of propranolol and statin further increases the risk, by including an interaction term for use of propranolol and statins.
RESULTS: We identified 9,304 initiators of propranolol and 130,070 initiators of other BBs and found 30 cases of hospitalized myopathy in 15,477 person-years (PYs) of propranolol use and 523 in 343,132 PYs of other BB use. Comparing propranolol with other BB users, the adjusted hazard ratio was 1.45 (95% CI 1.00-2.11) for myopathy and 1.48 (95% CI 0.82-2.67) for rhabdomyolysis. We could not detect interaction between propranolol and statins due to limited power. Similar results were observed when propranolol users were compared to other antihypertensive drug users.
CONCLUSIONS: Propranolol may be associated with a 45% increased risk of hospitalized myopathy in the elderly. Our study illustrates how results from in vitro chemical screens can be translated into hypotheses about drug toxicity at the population level.