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

Abstract

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.

• Authors: Soko Setoguchi, John M Higgins, Helen Mogun, Vamsi K Mootha, Jerry Avorn
• Journal: American heart journal (Am Heart J) Vol. 159 Issue 3 Pg. 428-33 (Mar 2010) ISSN: 1097-6744 [Electronic] United States
• PMID: 20211305 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Propranolol

Topics

• Adrenergic beta-Antagonists (adverse effects)
• Aged
• Aged, 80 and over
• Drug Synergism
• Female
• Hospitalization (statistics & numerical data)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects)
• Incidence
• Male
• Muscular Diseases (chemically induced, epidemiology, therapy)
• Proportional Hazards Models
• Propranolol (adverse effects)
• Rhabdomyolysis (chemically induced, epidemiology, therapy)