Measuring Quality and Performance in Treatment of Heart Failure in African-American Patients: V-HeFT and the Road to A-HeFT Peter Carson M.D.

Transcription

1 Measuring Quality and Performance in Treatment of Heart Failure in African-American Patients: V-HeFT and the Road to A-HeFT Peter Carson M.D.

2 Chronology of ISDN/Hydralazine ISDN/HYD V-HeFT I BIDIL Sub-group Analyses A-HeFT FDA (Paper NDA) FDA (BIDIL) FDA (Sub-group)

3 Heart Failure Therapy the beginning

4 Vasodilator Therapy

5 Chest. 1978;73:8-13. NITRO0010 AHeFT Slides v11 5

6 V-HeFT Inclusions/Exclusions Men between the ages of 18 and 75. Veterans Hospitals Cardiac dilatation (cardiothoracic ratio >0.55 on chest x-ray film or a left ventricular internal diameter in diastole >2.7 cm per square meter on echocardiography) or radionuclide LVEF <45 percent reduced exercise tolerance (peak <25 ml per kg of body weight per minute) -excluded if exercise tolerance was limited by chest pain rather than by breathlessness and fatigue. Exclusions - a myocardial infarction within the previous 3 months, obstructive valvular disease or considerable CAD, COPD, or other disease likely to limit five-year survival. No concomitant CV meds- BB, RAS inhibitors, vasodilators

7 Survival, % 9 Survival in All Patients V-HeFT I ISDN/HYD Placebo Prazosin 50 P = ISDN/HYD vs placebo Days since randomization date ISDN/HYD n = Placebo n = Prazosin n = ISDN/HYD = isosorbide dinitrate plus hydralazine Cohn JN et al. N Engl J Med. 1986;314:

8 Survival, % 2 6 Survival in All Patients V-HeFT II Enalapril lsdn/hyd HR = 1.23 (0.97, 1.55) Log-rank P = Time, days since randomization ISDN/HYD n = Enalapril n = Cohn JN et al. N Engl J Med. 1991;325:

9 Percent Patients Achieving Blood Pressure Goal (< 91 mmhg) Effect of Captopril on BP Whites Blacks Placebo Captopril 12.5 mg Captopril 25.0 mg Captopril 37.5 mg Captopril 50.0 mg

10 V-HeFT II: Baseline Variables Ejection fraction (%) MVO 2 (ml / Kg / min) SBP sitting (mmhg) PNE (pg / ml) PRA (ng / ml / hr) Cardiothoracic ratio CAD (%) Hx HTN (%) Black (n = 215) 29.2 ± ± ± ( ) 6.55 ( ) 54.3 ± White (n = 574) 29.0 ± ± 3.5 * ± ( ) ** 7.3 ( ) 52.2 ± 6 * 61.6 ** 41.5 ** PNE = plasma norepinephrine; PRA = plasma renin activity * = p < 0.05; ** = p < 0.01

11 Survival, % Survival, % Survival in Black Patients and White Patients V-HeFT II Black patients White patients ISDN/HYD Enalapril HR = 1.01 (0.65, 1.58) P = Patients, n Time, days since randomization ISDN/HYD Enalapril Carson P et al. J Card Fail. 1999;5: HR = 1.39 (1.05, 1.83) P =

12 Cumulative Mortality Cumulative Mortality Cumulative Mortality Cumulative Mortality V - HeFT II: Mortality by Race and Hypertensive History White Patients w / o Hypertensive History (n = 318) p < Months Black Patients w / o Hypertensive History (n = 72) Hyd - Iso Enalapril p < Months White Patients with Hypertensive History (n = 218) p < Months Black Patients with Hypertensive History (n = 132) p < Months

13 V-HeFT ll Remodeling

14 V-HeFT ll Data

15 Survival, % 9 Survival in All Patients V-HeFT I ISDN/HYD Placebo Prazosin 50 P = ISDN/HYD vs placebo Days since randomization date ISDN/HYD n = Placebo n = Prazosin n = ISDN/HYD = isosorbide dinitrate plus hydralazine Cohn JN et al. N Engl J Med. 1986;314:

16 V-HeFT I: Baseline Variables Ejection fraction (%) SBP sitting (mmhg) Age (years) Cardiothoracic ratio CAD (%) Hx HTN (%) Black (n = 180) 31.3 ± ± ± ± White (n = 480) 29.3 ± ± ± 6.9 ** 52.7 ± 6.3 ** 50.2 ** 37.3 * * = p < 0.05; ** = p < 0.01 Black vs White CAD = coronary artery disease hx HTN = history of hypertension

17 Survival, % Survival, % Survival in Black Patients and White Patients V-HeFT I 100 Black patients 100 White patients ISDN/HYD Placebo HR = 0.53 (0.29, 0.98) P = HR = 0.88 (0.63, 1.24) P = Patients, n Time, days since randomization ISDN/HYD Placebo Carson P et al. J Card Fail. 1999;5:

18 CHF Hospitalization Race Subgroup White Black V - HeFT I Placebo HYD - ISO Prazosin Total Placebo HYD - ISO Prazosin Total Total Hospitalized CHF 49 (25.5 %) 40 (31.5 %) 32 (24.2 %) (25.5 %) 12 (25.5 %) 12 (25.5 %) 39 V - HeFT II Enalapril HYD - ISO Total Enalapril HYD - ISO Total Total Hospitalized CHF 51 (18.1 %) 51 (17.5 %) (22.6 %) 23 (21.1 %) 47

19 V-HeFT and the Road to A-HeFT The V-HeFT retrospective analysis indicated mortality benefit in African- American patients. There was a physiologic rationale developing related to NO Like all post-hoc analyses, this needed to be prospectively tested for validity. IT WAS!

20 Survival (%) A-HeFT: All-Cause Mortality 43% Decrease 100 ISDN/HYD FDC Hazard ratio=0.57 P=0.01 Placebo Fixed-dose H/I Placebo Taylor AL et al. N Engl J Med. 2004;351: Days Since Baseline Visit Date

21

22 Racial Differences in the Outcome of Left Ventricular Dysfunction Dries et al, NEJM 1999; 340:

23 Outcomes among Black Patients as Compared with Matched White Patients. Exner DV et al. N Engl J Med 2001;344:

24 Outcomes among Black and Matched White Patients Assigned to Enalapril Therapy as Compared with Placebo. Exner DV et al. N Engl J Med 2001;344:

25 Rates of Death from Any Cause (Top Panel) and of Hospitalization for Heart Failure (Bottom Panel) among Black Patients and Matched White Patients Randomly Assigned to Enalapril or Placebo. Exner DV et al. N Engl J Med 2001;344: