Risk of Hospitalization for Cardiovascular Events with β-Blockers in Hypertensive Patients: A Retrospective Cohort Study

INTRODUCTION: β-Blockers are a heterogenous class of drugs that are no longer recommended for initial antihypertension monotherapy due to unfavorable long-term cardiovascular events observed with non-vasodilatory β-blockers. However, the comparative cardiovascular event risk between the vasodilatory β(1)-selective antagonist/β(3) agonist nebivolol and non-vasodilatory β(1)-blockers, atenolol and metoprolol, is unknown. METHODS: Incident nebivolol, atenolol, or metoprolol monotherapy users with hypertension were identified using US claims data (2007–2014). The first β-blocker claim on/after 1/1/2008 defined the index drug/date. Hypertensive patients without pre-index cardiovascular history were followed until index drug discontinuation (> 90 day supply gap), use of other β-blockers, or end of continuous plan enrollment. Patients were pair-wise propensity score-matched using logistic regression, adjusted for baseline demographics, Charlson Comorbidity Index score, comorbid chronic pulmonary disease, rheumatic disease, renal disease, and diabetes, and use of other antihypertensive drugs during baseline. Time to first hospital claim for a cardiovascular event was assessed via Cox proportional hazards regression, adjusted for the variables above. RESULTS: Inclusion criteria were met by 81,402 patients (n = 27,134 in each matched treatment cohort), with no between-cohort differences in baseline characteristics, comorbid conditions, or average follow-up duration. Atenolol and metoprolol cohorts had greater risk of hospitalization for a composite event (myocardial infarction, angina, congestive heart failure, stroke) than nebivolol users (adjusted hazard ratios [95% confidence interval] atenolol: 1.68 [1.29, 2.17]; metoprolol: 2.05 [1.59, 2.63]; P < 0.001, both). Risks of most individual cardiovascular events were also lower with nebivolol, including myocardial infarction and angina versus atenolol, and myocardial infarction, congestive heart failure, and angina versus metoprolol (P < 0.05, all). CONCLUSIONS: Nebivolol was associated with significantly lower risk of hospitalization due to composite cardiovascular events than atenolol or metoprolol in this large retrospective cohort study of monotherapy with three different β(1)-selective blockers in hypertensive patients. FUNDING: Allergan plc, Madison, NJ, USA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40119-018-0117-y) contains supplementary material, which is available to authorized users.