The Impact of Antihypertensive De-escalation: A Secondary Analysis of SPRINT

BackgroundAntihypertensive de-escalation--reducing the number of antihypertensive medications--is sometimes warranted but may increase cardiovascular risk if not clinically appropriate. Our study investigated the impact of antihypertensive de-escalation without clinical consideration on cardiovascular outcomes and adverse events. MethodThis is a secondary analysis of Systolic Blood Pressure Intervention Trial (SPRINT), a randomized open-label trial, compared intensive (target systolic blood pressure (SBP) <120mmHg) vs. standard (target SBP <140mmHg) antihypertensive strategies. Before randomization, some patients underwent antihypertensive de-escalation to increase SBP into 130-180mmHg for eligibility. The exposure was de-escalation versus control, measured by the change in the number of antihypertensive medications between the screening visit and randomization. The primary outcome was major cardiovascular events (MACE), comprising myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular cause death. Secondary outcomes included myocardial infarction, stroke, heart failure, and all-cause mortality. Adverse events include hypotension, syncope, acute kidney injury, bradycardia, and electrolyte abnormalities. ResultsThe number of patients in de-escalation and control groups were 427 vs. 4,007 in the intensive arm, and 794 vs. 3,733 in the standard arm. De-escalation patients had higher baseline cardiovascular risk. In the standard arm, de-escalation was associated with increased MACE risk (HR 1.34, 95% CI: 1.04-1.74). In contrast, no excess MACE risk was observed in the intensive arm (SBP <120 mmHg). ConclusionAntihypertensive de-escalation without clinical consideration is associated with an increased risk of MACE. It reassures the importance of intensive SBP on patients at high cardiovascular risk and indicates a more intensive SBP target may be needed.