Isosorbide dinitrate, with or without hydralazine, did not improve reflection magnitude (P=0.64 for ISDN) and caused more adverse events than placebo (60.0-61.5% vs 12.5%; P=0.007).
RCT (n=44)
Double-blind
Does isosorbide dinitrate, with or without hydralazine, reduce wave reflections or improve ventricular remodeling in patients with heart failure with preserved ejection fraction?
Isosorbide dinitrate, with or without hydralazine, does not improve hemodynamics or ventricular remodeling in HFpEF and is poorly tolerated, arguing against their routine use in this population.
p-value: p=0.64 for ISDN; 0.03 for ISDN+hydralazine
Background Wave reflections, which are increased in patients with heart failure with preserved ejection fraction, impair diastolic function and promote pathologic myocardial remodeling. Organic nitrates reduce wave reflections acutely, but whether this is sustained chronically or affected by hydralazine coadministration is unknown. Methods and Results We randomized 44 patients with heart failure with preserved ejection fraction in a double‐blinded fashion to isosorbide dinitrate ( ISDN ; n=13), ISDN +hydralazine ( ISDN +hydral; n=15), or placebo (n=16) for 6 months. The primary end point was the change in reflection magnitude ( RM ; assessed with arterial tonometry and Doppler echocardiography). Secondary end points included change in left ventricular mass and fibrosis, measured with cardiac magnetic resonance imaging, and the 6‐minute walk distance. ISDN reduced aortic characteristic impedance (mean baseline=0.15 95% CI , 0.14–0.17, 3 months=0.11 95% CI , 0.10–0.13, 6 months=0.10 95% CI , 0.08–0.12 mm Hg/mL per second; P =0.003) and forward wave amplitude (P f , mean baseline=54.8 95% CI , 47.6–62.0, 3 months=42.2 95% CI , 33.2–51.3; 6 months=37.0 95% CI , 27.2–46.8 mm Hg, P =0.04), but had no effect on RM ( P =0.64), left ventricular mass ( P =0.33), or fibrosis ( P =0.63). ISDN +hydral increased RM (mean baseline=0.39 95% CI , 0.35–0.43; 3 months=0.31 95% CI , 0.25–0.36; 6 months=0.44 95% CI , 0.37–0.51, P =0.03), reduced 6‐minute walk distance (mean baseline=343.3 95% CI , 319.2–367.4; 6 months=277.0 95% CI , 242.7–311.4 meters, P =0.022), and increased native myocardial T1 (mean baseline=1016.2 95% CI , 1002.7–1029.7; 6 months=1054.5 95% CI , 1036.5–1072.3, P =0.021). A high proportion of patients experienced adverse events with active therapy ( ISDN =61.5%, ISDN +hydral=60.0%; placebo=12.5%; P =0.007). Conclusions ISDN , with or without hydralazine, does not exert beneficial effects on RM , left ventricular remodeling, or submaximal exercise and is poorly tolerated. ISDN +hydral appears to have deleterious effects on RM , myocardial remodeling, and submaximal exercise. Our findings do not support the routine use of these vasodilators in patients with heart failure with preserved ejection fraction. Clinical Trial Registration URL : www.clinicaltrials.gov . Unique identifier: NCT 01516346.
Zamani et al. (Thu,) conducted a rct in Heart failure with preserved ejection fraction (n=44). Isosorbide dinitrate (ISDN) with or without hydralazine vs. Placebo was evaluated on Change in reflection magnitude (RM) (p=0.64 for ISDN; 0.03 for ISDN+hydralazine). Isosorbide dinitrate, with or without hydralazine, did not improve reflection magnitude (P=0.64 for ISDN) and caused more adverse events than placebo (60.0-61.5% vs 12.5%; P=0.007).