Background and objectives: 2018 ESC/ESH Hypertension guideline recommends 2-drug combination as initial anti-hypertensive therapy. However, real-world evidence for effectiveness of recommended regimens remains limited. We aimed to compare the effectiveness of first-line anti-hypertensive treatment combining 2 out of the following classes: angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor blocker (A), calcium channel blocker (C), and thiazide-type diuretics (D).
Methods: Treatment-naïve hypertensive adults without cardiovascular disease (CVD) who initiated dual anti-hypertensive medications were identified in 5 databases from US and Korea. The patients were matched for each comparison set by large-scale propensity score matching. Primary endpoint was all-cause mortality. Myocardial infarction, heart failure, stroke, and major adverse cardiac and cerebrovascular events as a composite outcome comprised the secondary measure.
Results: A total of 987,983 patients met the eligibility criteria. After matching, 222,686, 32,344, and 38,513 patients were allocated to A+C vs. A+D, C+D vs. A+C, and C+D vs. A+D comparison, respectively. There was no significant difference in the mortality during total of 1,806,077 person-years: A+C vs. A+D (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.97-1.20; p=0.127), C+D vs. A+C (HR, 0.93; 95% CI, 0.87-1.01; p=0.067), and C+D vs. A+D (HR, 1.18; 95% CI, 0.95-1.47; p=0.104). A+C was associated with a slightly higher risk of heart failure (HR, 1.09; 95% CI, 1.01-1.18; p=0.040) and stroke (HR, 1.08; 95% CI, 1.01-1.17; p=0.040) than A+D.
Conclusions: There was no significant difference in mortality among A+C, A+D, and C+D combination treatment in patients without previous CVD. This finding was consistent across multi-national heterogeneous cohorts in real-world practice.
Keywords: Angiotensin receptor antagonists; Antihypertensive agents; Calcium channel blockers; Diuretics; Hypertension.
Copyright © 2020. The Korean Society of Cardiology.
Conflict of interest statement
The authors declare the following disclosures: Mr. Swerdel, Dr. Ryan, and Dr. Schuemie are employees of Janssen Research & Development. The rest of the authors declare no conflict of interest.
Outcomes With Angiotensin-converting Enzyme Inhibitors vs Other Antihypertensive Agents in Hypertensive BlacksS Bangalore et al. Am J Med 128 (11), 1195-203. PMID 26071821.In a real-world cohort of hypertensive blacks, angiotensin-converting enzyme inhibitors were associated with a higher risk of cardiovascular events when compared with cal …
Beta-blockers for HypertensionCS Wiysonge et al. Cochrane Database Syst Rev (1), CD002003. PMID 17253471. - ReviewThe available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak eff …
First-line Drugs for HypertensionJM Wright et al. Cochrane Database Syst Rev 4 (4), CD001841. PMID 29667175. - ReviewFirst-line low-dose thiazides reduced all morbidity and mortality outcomes in adult patients with moderate to severe primary hypertension. First-line ACE inhibitors and c …
Association Between Cardiovascular Outcomes and Antihypertensive Drug Treatment in Older WomenS Wassertheil-Smoller et al. JAMA 292 (23), 2849-59. PMID 15598916.Among women with hypertension but no history of CVD, a 2-drug-class regimen of calcium channel blockers plus diuretics was associated with a higher risk of CVD mortality …
Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. JAMA 288 (23), 2981-97. PMID 12479763. - Clinical TrialThiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy. …