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Objectives: Hypertension is a major risk factor for cardiovascular (CV) events. While β-blockers (BBs) lower blood pressure and reduce CV event risk, the comparative CV event risk and rate of hospitalization due to CV events between hypertensive patients treated with vasodilatory β1-selective antagonist/β3 agonist, nebivolol (NEB), and non-vasodilatory β1-selective BBs, atenolol (ATN) and metoprolol (MET), is unknown.Methods: Incident users of NEB, ATN or MET receiving ≥1 additional antihypertensive were identified from US claims data (2007-2014). First BB claim on/after 1/1/2008 defined index drug and date. Follow-up lasted ≥6 months, until index drug cessation or other BB use. Treatment cohorts (N=16,787 each) were matched by the number of antihypertensive drug classes used in follow-up and on propensity score (1:1) to balance confounders (follow-up duration, baseline demographics and clinical characteristics). Clinical outcomes based on matched cohorts were: hospitalization risk for composite CV outcome (myocardial infarction [MI], congestive heart failure, stroke, and angina; assessed by Cox proportional hazards regression) and event rate ratio for CV-related hospitalizations (assessed by count regression with negative binomial distribution) comparing ATN and MET with NEB. Both regressions were adjusted for concomitant antihypertension medication possession ratios (≥75%) and baseline confounders balanced in matching.Results: Compared with NEB, hospitalization risk due to composite CV events, MI, and angina was significantly higher with ATN and MET (Table). The unadjusted rate of all hospitalizations due to composite CV events per 1,000 persons per year was significantly greater in ATN and MET users compared with NEB users, while the adjusted ratio of composite CV event rate was significantly greater with MET, but not ATN (Table).Conclusions: In adults receiving combination antihypertension therapy, NEB treatment was associated with a lower risk for CV-related hospitalization than either ATN or MET. Lower risk of hospitalization was supported by event rate data, as patients receiving NEB combined with other antihypertensives were hospitalized less frequently than patients receiving combination therapy with either ATN or MET.