Blood Pressure Variability and Outcomes Across Antihypertensive Regimens

BACKGROUND: Blood pressure (BP) variability (BPV) is associated with cardiovascular risk beyond mean 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 2 randomized trials: ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) and SPRINT (Systolic Blood Pressure Intervention Trial). Propensity score matching was used for pairwise comparisons of RAS (renin–angiotensin system) 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. Secondary outcomes included major adverse cardiovascular events and its individual components. RESULTS: The final cohort included 5779 participants (median of 12 BP measurements and median follow-up of 3.5 years), among whom 2754 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 versus RAS: β=−1.341 95% CI, −1.930 to −0.752; P <0.001) and combination therapies (CCB+diuretic versus 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%) major adverse cardiovascular event events were observed in the overall cohort. No significant differences in major adverse cardiovascular event 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.