Impact of antihypertensive drug classes on cardiovascular outcomes: insights from the STEP study

The optimal class of antihypertensive drugs for reducing cardiovascular risk remains unclear. This study investigated whether prolonged exposure to specific antihypertensive drug classes is associated with lower cardiovascular risk in individuals with well-controlled blood pressure.

This study utilised data from the STEP trial, which enrolled elderly, hypertensive Chinese patients with no history of stroke. After excluding 234 patients lost to follow-up and 20 patients without blood pressure records after randomisation, 8257 patients were included. The relative time on each antihypertensive drug (medication time/event time) was calculated. The primary outcome was a composite of the first occurrence of stroke, acute coronary syndrome (ACS), acute decompensated heart failure, coronary revascularisation, atrial fibrillation, and cardiovascular death. Secondary endpoints included individual components of the primary outcome. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome.

Over a median 3.34 years follow-up, primary outcome analysis revealed that longer relative exposure to angiotensin II receptor blockers (ARBs) or calcium channel blockers (CCBs) significantly reduced cardiovascular risk. Each unit increase in relative time on ARBs was associated with a 45% lower risk of the primary outcome (HR 0.55, 95% CI 0.43-0.70), whereas CCBs reduced risk by 30% (HR 0.70, 95% CI 0.54-0.92). Diuretics demonstrated neutral results. Conversely, longer relative time on beta-blockers was linked to a higher primary outcome risk (HR 2.20, 95% CI 1.81-2.68). Regarding secondary outcomes, extended exposure to both ARBs and CCBs was significantly associated with lower risks of all-cause and cardiovascular mortality. Longer exposure to ARBs produced additional benefits by reducing risks of stroke, ACS, and major adverse cardiac events (MACE). The HRs for ARBs per-unit increase in relative time remained consistently lower than those of CCBs across the primary outcome, MACE, and stroke (all P < 0.05).

This post hoc analysis suggested that ARBs and CCBs might be more favourable for composite cardiovascular outcomes than diuretics and beta-blockers. ARBs appeared to offer greater cardiovascular benefits than CCBs. Longer exposure to beta-blockers was associated with a higher cardiovascular risk, which might reflect a selection bias based on medical indications.

STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.