The Impact of Antihypertensive De-escalation: A Secondary Analysis of Systolic Blood Pressure Intervention Trial (SPRINT)

Introduction Antihypertensive de-escalation—reducing the number of antihypertensive medications—is sometimes warranted but may increase cardiovascular risk. Aim To evaluate the association of antihypertensive de-escalation with major adverse cardiovascular events (MACE) in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods Our secondary analysis of SPRINT included participants randomized to intensive (target systolic blood pressure [SBP] <120 mm Hg) vs. standard (target SBP <140 mm Hg) antihypertensive strategies. Before randomization, some patients underwent antihypertensive de-escalation to increase SBP into 130-180 mm Hg for eligibility. The exposure was antihypertensive de-escalation, defined as a reduction in the number of antihypertensive medications between screening and randomization; the control group included participants without such a reduction. The primary outcome was major cardiovascular events (MACE), comprising myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular cause death. Results The number of patients in de-escalation and control groups were 794 vs. 3,733 (standard arm) and 427 vs. 4,007 (intensive arm). De-escalation patients had higher baseline cardiovascular risk. In the standard arm (target SBP <140 mm Hg), de-escalation was followed by delayed treatment re-intensification, with only 52.9% of de-escalation patients returned to their medication count at screening visit after a mean of 358.0 days following randomization. In contrast, 76.6% of de-escalation patients in the intensive arm (target SBP <120 mm Hg) returned to their screening medication count, with a shorter mean time of 197.9 days. De-escalation followed by delayed treatment re-intensification under the standard treatment strategy was associated with an increased MACE risk (HR: 1.34, 95% CI: 1.04–1.74) than control patients. Conversely, no excess MACE risk was observed among de-escalation patients in the intensive arm, where treatment was promptly re-intensified after de-escalation under an intensive SBP target (<120 mm Hg). Conclusions Antihypertensive de-escalation, followed by delayed treatment re-intensification, is associated with an increased risk of MACE. These findings reassure the benefit of continuous intensive SBP control and timely re-intensification treatment after de-escalation, especially in patients at high cardiovascular risk.