Heart Failure Prevention in Older Patients Using Intensive Blood Pressure Reduction: Potential Role of Diuretics

Abstract

Objectives: This study assessed the potential role of differential diuretic drugs in preventing incident acute decompensated heart failure (ADHF) in the SPRINT (Systolic Blood Pressure Intervention Trial) study.

Background: SPRINT showed that intensive blood pressure reduction in older patients (50 to 97 years of age) resulted in 36% fewer incident cases of ADHF. However, some investigators have questioned whether this was due merely to intergroup differences in diuretic medications.

Methods: Detailed use of medication data prospectively collected throughout the trial were examined.

Results: ADHF events occurred in 173 of 9,361 participants. Diuretic medication increased in both arms from screening to baseline visit (from 45% to 50% in the standard arm; and from 43% to 63% in the intensive arm) and then remained steady. The lowest use of diuretic agents was among participants in the standard arm who never had an ADHF event. Withdrawal of diuretic agents at the baseline visit occurred in 6.1% (n = 284) of participants in the standard arm and 2.3% (n = 107) of participants in the intensive arm. Of these, only 11 developed ADHF during the trial (10 in the standard arm, 1 in the intensive arm), and only 1 occurred ≤1 month after diuretic withdrawal. The benefit of ADHF reduction remained significant even after excluding those 11 participants (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.5 to 0.94; p = 0.02). Most ADHF events occurred in participants who were taking prescribed diuretic therapy at the last visit, prior to the ADHF event. There was limited use of loop (<6%) and potassium-sparing diuretic agents (2%). Diuretic use was not a predictor of ADHF (HR: 0.96; 95% CI: 0.66 to 1.40; p = 0.83).

Conclusions: No evidence was found to suggest that the reduction in new ADHF events in SPRINT was due to differential diuretic use. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).

Keywords: SPRINT clinical trial; aging; diuretics; heart failure; systolic hypertension.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. Kaplan–Meier curves for development of ADHF by treatment group.

Vertical bars indicate 95% confidence intervals. P-value is from Cox proportional hazards model stratified by clinical site. Number at risk and number of events shown every 6 months.

Figure 2:. Percentage of participants prescribed diuretics at each time point by treatment arm.

X-axis shows visit number in months from screening visit(000) and baseline visit(00R) to 60-months after baseline visit. Y-axis shows percentage of participants prescribed any diuretic.

Figure 3.. Scatter plot showing number of months until ADHF event for participants who developed ADHF after withdrawal of diuretics at baseline visit.

X-axis shows visit number in months; Y-axis shows percentage of participants prescribed any diuretic. Plot depicts four combinations of development of heart failure and treatment arm

Figure 4.. Percentage of participants prescribed diuretics by treatment arm at each time point.

X-axis shows visit number in months; Y-axis shows percentage of participants prescribed any diuretic. Plot depicts four combinations of development of heart failure and treatment arm

Central Illustration.. Intensive BP Reduction for Preventing Heart Failure: Potential Role of Diuretics.

SPRINT showed that intensive blood pressure reduction in older patients results in 36% fewer incident acute decompensated heart failure events (ADHF). However, some have questioned whether this was due merely to intergroup differences in diuretic medications. Detailed medication use data prospectively collected throughout the trial were examined and we found no evidence that the reduction in new ADHF events in SPRINT was due to differential diuretic use.