PowerPoint Presentation PARADIGM HF 2 METHODS Thiết kế Đặc điểm ban đầu của BN Tình trạng bệnh nhân qua các phase Diễn tiến Tiêu chí chính và tiêu chí phụ • NYHA class II IV heart failure • LV ejectio[.]
2 PARADIGMHF METHODS - Thiết kế - Đặc điểm ban đầu BN - Tình trạng bệnh nhân qua phase - Diễn tiến Tiêu chí tiêu chí phụ PARADIGM-HF: Tiêu chuẩn nhận bệnh • NYHA class II-IV heart failure • LV ejection fraction ≤ 40% 35% (amendment amendment Dec/2010) •BNP ≥ 150 (amendment or NT-proBNP ≥ 600), or BNP ≥ 100 (amendment or NTproBNP ≥ 400), if hospitalized for HF within 12 months • Any use of ACE inhibitor or ARB, but able to tolerate stable dose equivalent to at least enalapril 10 mg daily for at least weeks • Guideline-recommended use of beta-blockers and mineralocorticoid receptor antagonists •Systolic BP ≥ 95 mm Hg, eGFR ≥ 30 ml/min/1.73 m2 and serum K ≤ 5.4 mEq/L at randomization PARADIGM-HF: Đặc điểm bệnh nhân ban đầu LCZ696 Enalapril (n=4187) Age (amendment years) Women (amendment %) Ischemic cardiomyopathy (amendment %) LV ejection fraction (amendment %) NYHA functional class II / III (amendment %) Systolic blood pressure (amendment mm Hg) Heart rate (amendment beats/min) N-terminal pro-BNP (amendment pg/ml) B-type natriuretic peptide (amendment pg/ml) History of diabetes Digitalis Beta-adrenergic blockers Mineralocorticoid antagonists (n=4212) 63.8 ± 11.5 21.0% 59.9% 29.6 ± 6.1 71.6% / 23.1% 122 ± 15 72 ± 12 1631 (amendment 885-3154) 255 (amendment 155-474) 35% 29.3% 93.1% 54.2% 63.8 ± 11.3 22.6% 60.1% 29.4 ± 6.3 69.4% / 24.9% 121 ± 15 73 ± 12 1594 (amendment 886-3305) 251 (amendment 153-465) 35% 31.2% 92.9% 57.0% PARADIGM-HF: Thiết kế nghiên cứu Randomization Single-blind run-in period Double-blind period LCZ696 200 mg BID Enalapril LCZ696 (amendment 1:1 randomization) 10 mg BID 100 mg BID 200 mg BID Enalapril 10 mg BID weeks 1-2 weeks 2-4 weeks PARADIGM-HF: Lưu đồ nghiên cứu 10,521 patients screened at 1043 centers in 47 countries Did not fulfill criteria for randomization (amendment n=2079) Randomized erroneously or at sites closed due to GCP violations (amendment n=43) 8399 patients randomized for ITT analysis LCZ696 (amendment n=4187) At last visit 375 mg daily 11 lost to followup median 27 months of follow-up Enalapril (amendment n=4212) At last visit 18.9 mg daily lost to follow-up PARADIGM-HF: Tiêu chí - Phụ Tiêu chí chính: Tử vong tim mạch nhập viện suy tim 40 Enalapril Kaplan-Meier Estimate of Cumulative Rates (%) 32 111 (amendment n=4212) 24 LCZ696 (amendment n=4187) 16 HR = 0.80 (0.73-0.87) P = 0.0000002 Number needed to treat = 21 0 180 360 540 720 900 1080 1260 896 853 249 236 Days After Randomization Patients at Risk LCZ696 Enalapril 914 4187 4212 3922 3883 3663 3579 3018 2922 2257 2123 1544 1488 PARADIGM-HF: Tử vong tim mạch Kaplan-Meier Estimate of Cumulative Rates (%) 32 Enalapril HR = 0.80 (0.71 - 0.89) P = 0.00004 Number need to treat = 32 24 (amendment n=4212) 693 558 16 LCZ696 (amendment n=4187) 180 360 540 720 900 1080 1260 1005 994 280 279 Days After Randomization Patients at Risk LCZ696 Enalapril 4187 4212 4056 4051 3891 3860 3282 3231 2478 2410 1716 1726 PARADIGM-HF: Nhập viện suy tim 40 HR = 0.79 (0.71-0.89) P