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Heart Failure Project Groups 3 and 4.
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Heart Failure ProjectGroups 3 and 4 • Among people who self-identify themselves as non-African Americans, does the addition of isosorbidedinitrate/hydralazine (I/H) added to optimized background treatment for participants with heart failure and reduced ejection fraction reduce all-cause mortality as compared to placebo.
Study Rationale • Data from early trials done in men indicate that I/H may be an effect HF treatment. • A trial done in African Americans was stopped early due to a mortality difference favoring I/H. • Use of I/H is not common. • Morbidity and mortality due to HF remains high. • Comparative data on the efficacy of I/H for non-African Americans in the current era of treatments for HF do not exist.
V-HeFT I: All-cause Mortality in Black and White Patients Black patients White patients 100 100 95 95 HR=0.53 P=0.04 HR=0.88 P=0.47 90 90 85 85 80 80 75 75 70 70 Percent survival Percent survival 65 65 60 60 55 55 50 50 Treatment Group H-I (H) Placebo (P) Treatment Group H-I (H) Placebo (P) 45 45 40 40 35 35 30 30 0 P (N=79) H (N=49) 365 P (N=61) H (N=43) 730 P (N=44) H (N=36) 1095 P (N=29) H (N=28) 1460 P (N=14) H (N=16) 1825 P (N=14) H (N=16) 0 P (N=192) H (N=132) 365 P (N=140) H (N=102) 730 P (N=91) H (N=71) 1095 P (N=55) H (N=42) 1460 P (N=27) H (N=22) 1825 P (N=8) H (N=9) Days since randomization date Days since randomization date Carson P, et al. J Cardiac Fail. 1999;5:178-187.
V-HeFT II: All-cause Mortality in Black and White Patients Black patients White patients 100 100 95 95 HR=1.01 P=NS HR=1.32 P=0.02 90 90 85 85 80 80 75 75 70 70 Percent survival Percent survival 65 65 60 60 55 55 50 50 Treatment Group H-I (H) Enalapril (E) Treatment Group H-I (H) Enalapril (E) 45 45 40 40 35 35 30 30 0 P (N=106) H (N=109) 365 P (N=93) H (N=92) 730 P (N=69) H (N=67) 1095 P (N=47) H (N=49) 1460 P (N=24) H (N=29) 1825 P (N=1) H (N=2) 0 P (N=292) H (N=282) 365 P (N=251) H (N=231) 730 P (N=194) H (N=171) 1095 P (N=123) H (N=105) 1460 P (N=66) H (N=55) 1825 P (N=1) H (N=1) Days since randomization date Days since randomization date Carson P, et al. J Cardiac Fail. 1999;5:178-187.
A-HeFT: 43% Decrease in Mortality 100 Isosorbide dinitrate/hydralazine 95 Survival (%) 90 Placebo HR=0.57 P=0.01 85 0 100 200 300 400 500 600 Days since baseline visit ISDN/HYD518 463 407 359 313 251 13 Placebo 532 466 401 340 285 232 24 Taylor AL, et al. N Engl J Med. 2004;351:2049-2057.
Questions To Consider • Inclusion criteria • Impact of resynchronization therapy on event rates. • Major outcomes to consider • How to conduct the study simply and cost-efficiently (e.g., large, simple trial)