MERITHF Vs COPERNICUS Ddsfall ved studieslutt

1
(No Transcript)
2
MERIT-HF Vs COPERNICUSDødsfall ved studieslutt

• MERIT HF
• SELO Zok? Placebo
• 11,7 19,1
• (45) (72)
• Risk red. 39
• CI 95 0.42 0.89 (p 0.0086)

Post-hoc subbanalyse basert på resultater fra
MERIT-HF studien. Grafikk og tabeller utarbeidet
av AstraZenica The International Steering
Committee on Behalf of the MERIT-HF Study
Group Am J Cardiol 199780(9b)54J-58J, Lancet
19993532001-07 Data fra COPERNICUS studien
Hjerteforum 2000470-71
3
Angiotensin II is produced both by ACE and
non-ACE dependent pathways
Chymase CAGE
4
Dokumentasjon på mortalitetACE-hemmere kronisk
svikt
5
Dokumentasjon på mortalitetACE-hemmere
Postinfarkt
PMN963
6
Losartan Heart Failure Survival StudyELITE II
?
7
The Losartan Heart Failure Survival StudyELITE
IIPrimary Endpoint All-Cause Mortality

• No significant difference between losartan and
  captopril in reducing all-cause mortality in
  heart failure

Kaplan-Meier Estimates for Survival
Losartan (n1578)Captopril (n1574)
Probability of survival
Hazard ratio (95.7 CI)1.13 (0.95, 1.35)
p0.16)
0 100 200 300 400 500 600 700
Days of follow-up
CI confidence interval Adapted from Pitt B et
al Lancet 20003551582-1587.
8
Optimal Trial in MI with the AIIA losartan

• Design Multinational, Double-blind,
  randomized, parallel, captopril-controlled
• Patients ? 50 years of age, AMI-patients with
  heart failure or anterior Q-wave AMI
• Primary endpoint All-cause mortality
• Sample size n 5000
• Statistics 2p lt 0.05, powe 95, 937 deaths,
• difference in primary endpoint to detect 20

9
OPTIMAAL RESULTAT
10
Study Design- VAL-HEFT
?
11
Primary Endpoint Analysis
All Cause Mortality
Combined All Cause Mortality Morbidity
12
VALIANT
13
The renin-angiotensin system
14
Aldosteronets rolle ved hjertesvikt
15
(No Transcript)
16
(No Transcript)
17
(No Transcript)
18
(No Transcript)
19
(No Transcript)
20
CHARM Programme
3 component trials comparing candesartan to
placebo in patients with symptomatic heart failure
n2028 LVEF ?40ACE inhibitor intolerant
n2548 LVEF ?40ACE inhibitor treated
n3025 LVEF gt40ACE inhibitor treated/not
treated
Primary outcome for each trial CV death or CHF
hospitalisation
Primary outcome for Overall Programme All-cause
death
21
CHARM-Alternative Primary outcome CV death or
CHF hospitalisation

50
406 (40.0)
Placebo
40
334 (33.0)
30
Candesartan
20
10
HR 0.77 (95 CI 0.67-0.89), p0.0004Adjusted HR
0.70, plt0.0001
0
0
1
2
3
years
3.5
Number at risk Candesartan 1013 929 831 434 122 P
lacebo 1015 887 798 427 126
22
CHARM-Alternative Secondary outcomes
p-value
Candesartan
Placebo
0.85
CV death 219 252 CHF hosp. 207 286 CV death,
CHF hosp, 353 420 MI CV death, CHF
hosp, 369 432 MI, stroke CV death, CHF
hosp, 396 456 MI, stroke, revasc
0.072
0.68
lt0.0001
0.78
0.0007
0.80
0.001
0.81
0.002
0.6
0.8
1.0
1.2
1.4
candesartan better
Hazard ratio
placebo better
23
CHARM-Added Primary outcomeCV death or CHF
hospitalisation

50
538 (42.3)
Placebo
40
483 (37.9)
30
Candesartan
20
10
HR 0.85 (95 CI 0.75-0.96), p0.011Adjusted HR
0.85, p0.010
0
0
1
2
3
years
3.5
Number at risk Candesartan 1276 1176 1063 948 457
Placebo 1272 1136 1013 906 422
24
CHARM-Added Secondary outcomes
p-value
Candesartan
Placebo
0.84
CV death 302 347 CHF hosp. 309 356 CV death,
CHF hosp, 495 550 MI CV death,CHF
hosp, 512 559 MI, stroke CV death,CHF
hosp, 548 596 MI, stroke, revasc
0.029
0.83
0.014
0.85
0.010
0.87
0.020
0.87
0.015
0.6
0.8
1.0
1.2
1.4
candesartan better
Hazard ratio
placebo better
25
CHARM-Preserved Primary outcome CV death or CHF
hospitalisation

30
366 (24.3)
Placebo
25
333 (22.0)
20
Candesartan
15
10
HR 0.89 (95 CI 0.77-1.03), p0.118Adjusted HR
0.86, p0.051
5
0
0
1
2
3
years
3.5
Number at risk Candesartan 1514 1458 1377 833 182
Placebo 1509 1441 1359 824 195
26
CHARM-Preserved Primary and secondary outcomes
Covariate adjustedp-value
Candesartan
Placebo
p-value
0.89
0.118
0.051
CV death, CHF hosp. 333 366 - CV death 170 170
- CHF hosp. 241 276 CV death, CHF
hosp, 365 399 MI CV death,CHF hosp, 388 429
MI, stroke CV death,CHF hosp, 460 497 MI,
stroke, revasc
0.99
0.918
0.635
0.85
0.072
0.047
0.90
0.126
0.051
0.88
0.078
0.037
0.91
0.123
0.13
0.8
1.0
1.2
candesartan better
Hazard ratio
placebo better
27
CHARM-OverallCHF hospitalisations
Placebo
Candesartan
Proportion of patients ()
Number of episodes
plt0.0001
plt0.0001
Hospitalisations
Patients hospitalised
28
CHARM-Overall Development of new diabetes
Number of cases () HR p-value Candesartan Place
bo (CI)n2715 n2721
163 (6) 202 (7) 0.78 0.020 (0.64-0.96)