Post-Read Methods.pptx

2
PARADIGMHF
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


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 4 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
2 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
9 lost to follow-up


PARADIGM-HF: Tiêu chí chính - Phụ


Tiêu chí chính: Tử vong tim mạch và nhập viện vì suy tim
40

Enalapril

Kaplan-Meier Estimate
of Cumulative Rates

(%)

32

111
7

(amendment n=4212)

24

LCZ696
(amendment n=4187)

16

HR = 0.80 (0.73-0.87)
P = 0.0000002
Number needed to treat = 21

8
0

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

8
0

(amendment n=4187)
0

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 do suy tim
40
HR = 0.79 (0.71-0.89)
P<0.001

Kaplan-Meier Estimate
of Cumulative Rates
(%)

30

Enalapril
(amendment n=4212) 658

20

537

LCZ696

10

(amendment n=4187)

0

0

180

360

540

720

900

1080

1260

896
853

249
236

Days After Randomization
Patients at Risk
LCZ696
Enalapril

4187
4212

3922
3883

3663
3579

3018
2922

2257
2123

154
1488


PARADIGM-HF: Tử vong do mọi nguyên nhân
32
HR = 0.84 (0.76-0.93)
P<0.0001

24

Kaplan-Meier Estimate
of Cumulative Rates
(%)

Enalapril

711

16

LCZ696
(amendment n=4187)

8
0

835

(amendment n=4212)

0

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