Evidence for the effectiveness and safety of the third-generation β-blockers other than atenolol in hypertension remains scarce. We assessed the effectiveness and safety of β-blockers as first-line treatment for hypertension using 3 databases in the United States: 2 administrative claims databases and 1 electronic health record-based database from 2001 to 2018. In each database, comparative effectiveness of β-blockers for the risks of acute myocardial infarction, stroke, and hospitalization for heart failure was assessed, using large-scale propensity adjustment and empirical calibration. Estimates were combined across databases using random-effects meta-analyses. Overall, 118 133 and 267 891 patients initiated third-generation β-blockers (carvedilol and nebivolol) or atenolol, respectively. The pooled hazard ratios (HRs) of acute myocardial infarction, stroke, hospitalization for heart failure, and most metabolic complications were not different between the third-generation β-blockers versus atenolol after propensity score matching and empirical calibration (HR, 1.07 [95% CI, 0.74-1.55] for acute myocardial infarction; HR, 1.06 [95% CI, 0.87-1.31] for stroke; HR, 1.46 [95% CI, 0.99-2.24] for hospitalized heart failure). Third-generation β-blockers were associated with significantly higher risk of stroke than ACE (angiotensin-converting enzyme) inhibitors (HR, 1.29 [95% CI, 1.03-1.72]) and thiazide diuretics (HR, 1.56 [95% CI, 1.17-2.20]). In conclusion, this study found many patients with first-line β-blocker monotherapy for hypertension and no statistically significant differences in the effectiveness and safety comparing atenolol with third-generation β-blockers. Patients on third-generation β-blockers had a higher risk of stroke than those on ACE inhibitors and thiazide diuretics.
Bibliographical noteFunding Information:
M.J. Schuemie and P.B. Ryan are employees of Janssen Research & Development—a subsidiary of Johnson & Johnson. C.G. Reich is an employee of IQVIA. H.M. Krumholz works under contract with the Centers for Medicare & Medicaid Services to develop publicly reported quality measures; was a recipient of a research grant, through Yale, from Medtronic and the US Food and Drug Adminis-
tration to develop methods for postmarket surveillance of medical devices; is a recipient of a research grant with Medtronic and Johnson & Johnson, through Yale, to develop methods of clinical trial data sharing; was a recipient of a research agreement, through Yale, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; received payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin Law Firm for work related to the Cook IVC filter litigation; receives payment from the Siegfried & Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for United-Health; is a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the cofounder of HugoHealth—a personal health information platform—and Refactor Health—an enterprise health care artificial intelligence-augmented data management company. D. Madigan has testified as an expert in litigation related to a number of drugs and devices but not related to any of the products considered in this study. G. Hripcsak and M.A. Suchard have received grant funding from Jans-sen through their universities to support methods research not directly related to this study. M.A. Suchard has also received contracts from Janssen and IQVIA for work not directly related to this study. S. Park has received grant funding and consultation fee from Daiichi Sankyo, which is not directly related to this study. S. Park has received speaking honoraria from Servier, Daiichi Sankyo, Hanmi, Daewoong, Pfizer, Takeda, Donga, and Boryoung, which is not directly related to this study. None of the sponsors and funders above including Janssen and IQVIA had input in the design, execution, interpretation of results, or decision to publish. The other authors report no conflicts.
This work was supported by the Bio Industrial Strategic Technology Development Program (20001234) funded by the Ministry of Trade, Industry and Energy (Korea) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant No. HI16C0992); a faculty research grant from Yonsei University College of Medicine (6-2019-0170 to S. Park); and from the Korean Centers for Disease Control and Prevention (2018-ER6302-01 to S. Park).
© 2021 American Heart Association, Inc.
All Science Journal Classification (ASJC) codes
- Internal Medicine