Comparative Analysis of First-Line Antihypertensive Treatment Classes

•Beta-blockers as first antihypertensives are associated with more cardiac events.•In patients younger than 50 years, thiazides were associated with better outcomes.•The difference between antihypertensives is evident after 3-4 years of treatment. The best first-line monotherapy for hypertension remains uncertain, as current guidelines suggest that thiazides, angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) are appropriate in the absence of specific comorbidities. We aimed to compare the outcomes of first-line antihypertensive classes in a real-life setting with a long follow-up period. This nationwide retrospective new-user cohort study included patients insured by the largest health maintenance organization in Israel. We included patients with a new diagnosis of hypertension between 2008 and 2021 who initiated treatment with a single first-line drug for hypertension. Outcomes were assessed with and without propensity score matching for confounding factors. The primary composite outcome was the first occurrence of myocardial infarction (MI), acute coronary syndrome (ACS), stroke, or heart failure (HF). A total of 97,639 patients initiated antihypertensive treatment with a single drug as first-line therapy. The most commonly prescribed class was ACEis/ARBs (66,717, 68.3%), followed by CCBs (15,922, 16.3%), beta-blockers (BBs, 12,869, 13.2%), and thiazides (2,131, 2.2%). For the primary outcome, the hazard ratios (HRs) for BBs, CCBs, and ACEis/ARBs were 1.44 (95% CI 1.25-1.66), 1.10 (95% CI 0.96-1.27), and 1.13 (95% CI 0.99-1.29), respectively, when compared to thiazides. When initiating pharmacotherapy for hypertension with a single drug, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers were associated with similar risk of MI, ACS, stroke, or HF when compared to thiazides, while beta-blockers were associated with increased risk. [Display omitted]