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

Background Antihypertensive 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.

This 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.

The 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).

Antihypertensive 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement No external funding was received. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Review Boards of the University of Florida. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Not available.