Effects of spironolactone on exercise blood pressure in patients at increased risk of developing heart failure: report from the HOMAGE trial

Abstract

None of the spironolactone trials in heart failure (HF) assessed the blood pressure (BP) responses to exercise, while conflicting results were reported for exercise capacity. In the HOMAGE trial, 527 patients at increased HF risk were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current substudy included 113 controls and 114 patients assigned spironolactone, who all completed the incremental shuttle walk test at baseline and months 1 and 9. Quality of life (QoL) was assessed by EQ5D questionnaire. Between-group differences (spironolactone minus control [Δs]) were analyzed by repeated measures ANOVA with adjustment for baseline and, if appropriate, additionally for sex, age and body mass index. Δs in the pre-exercise systolic/diastolic BP were -8.00 mm Hg (95% CI, -11.6 to -4.43)/-0.85 mm Hg (-2.96 to 1.26) at month 1 and -9.58 mm Hg (-14.0 to -5.19)/-3.84 mm Hg (-6.22 to -1.47) at month 9. Δs in the post-exercise systolic/diastolic BP were -8.08 mm Hg (-14.2 to -2.01)/-2.07 mm Hg (-5.79 to 1.65) and -13.3 mm Hg (-19.9 to -6.75)/-4.62 mm Hg (-8.07 to -1.17), respectively. For completed shuttles, Δs at months 1 and 9 were 2.15 (-0.10 to 4.40) and 2.49 (-0.79 to 5.67), respectively. Δs in QoL were not significant. The correlations between the exercise-induced BP increases and the number of completed shuttles were similar in both groups. In conclusion, in patients at increased risk of developing HF, spironolactone reduced the pre- and post-exercise BP, but did not improve exercise capacity or QoL.

Keywords: Coronary heart disease; Exercise capacity; Heart failure; Incremental shuttle walk test; Spironolactone.

Fig. 1

Consort diagram showing patient disposition, including screening, randomization and follow-up, and selection of patients for the current analysis. Analyses include 227 patients who completed the ISWT at months 0, 1, and 9. LVEF left ventricular ejection fraction; MRA mineralocorticoid receptor antagonism

Fig. 2

Changes from baseline to months 1 and 9 in the pre-exercise (A, B) and post-exercise (C, D) systolic (A, C) and diastolic (B, D) BP by randomization group. Data points are unadjusted mean changes ± SE. P values are for the comparison between intervention and control

Fig. 3

Systolic BP (A–C) and diastolic BP (D–F) pre-exercise, immediately post-exercise, and 1, 2, 3 and 5 min after exercise. Data points are unadjusted means ± SE. P-values for the between-group difference were computed by repeated measures ANOVA