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.
Setoguchi
Soko
S
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. ssetoguchi@partners.org
Higgins
John M
JM
Mogun
Helen
H
Mootha
Vamsi K
VK
Avorn
Jerry
J
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects*; D000368:Aged; D000369:Aged, 80 and over; D004357:Drug Synergism; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D009135:Muscular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000628:therapy*; D016016:Proportional Hazards Models; D011433:Propranolol / Q000009:adverse effects*; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000453:epidemiology / Q000628:therapy
D000319:Adrenergic beta-Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011433:Propranolol