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

Setoguchi, Soko; Higgins, John M.; Mogun, Helen; Mootha, Vamsi K.; Avorn, Jerry

doi:10.1016/j.ahj.2009.12.008

« Previous Next »American Heart Journal
Volume 159, Issue 3 , Pages 428-433, March 2010

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

Soko Setoguchi, MD, DrPH
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Boston, MA
- Reprint requests: Soko Setoguchi, MD, DrPH, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, 1620 Tremont St, Suite 3030, Boston, MA 02130.
- Cofirst authors.
John M. Higgins, MD
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
- Cofirst authors.
- Current address: Center for Systems Biology and Department of Pathology, Massachusetts General Hospital, and Department of Systems Biology, Harvard Medical School.
Helen Mogun, MS
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Boston, MA
Vamsi K. Mootha, MD
- Center for Human Genetic Research, Massachusetts General Hospital, Broad Institute of MIT and Harvard, and Department of Systems Biology, Harvard Medical School, Boston, MA
Jerry Avorn, MD
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Boston, MA

Received 9 June 2009; accepted 2 December 2009.

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 β-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.