Blood Pressure Variability and Outcomes Across Antihypertensive Regimens

Background: Blood pressure variability (BPV) is associated with cardiovascular risk beyond mean blood pressure (BP). Whether first-line antihypertensive regimens differentially affect BPV and cardiovascular outcomes remains uncertain. Methods: We conducted a target trial emulation using pooled individual participant data from two randomised trials: ACCORD-BP and SPRINT. Propensity score matching was used for pairwise comparisons of renin–angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics, as monotherapy or in combination. Follow-up was initiated at a predefined baseline medication assessment. The primary outcome was visit-to-visit systolic BPV, assessed using variation independent of the mean (VIM). Secondary outcomes included major adverse cardiovascular events (MACE) and its individual components. Results: The final cohort included 5,779 participants (median of 12 BP measurements and median follow-up of 3.5 years), among whom 2,754 were included in the matched analysis. CCB-based regimens were consistently associated with significantly lower systolic BPV compared with both RAS inhibitor-based and diuretic-based regimens. This association was consistent across monotherapy (CCB vs RAS: β=-1.341, 95% CI -1.930 to -0.752, P<0.001) and combination therapies (CCB+diuretic vs RAS+diuretic: β=-1.299, 95% CI -1.852 to -0.747, P<0.001). In contrast, RAS inhibitor–based and diuretic-based regimens demonstrated comparable BPV profiles. 215 (3.7%) MACE events were observed in the overall cohort. No significant differences in MACE or individual components were observed across comparisons. Conclusions: Among high-risk hypertensive patients receiving target-driven BP management, CCB-based regimens were associated with lower visit-to-visit systolic BPV compared with RAS inhibitor–based and diuretic-based regimens. However, these differences were not accompanied by detectable differences in cardiovascular outcomes.