Elite II by ert554898

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									         Effects of losartan compared with
      captopril on mortality in patients with
     symptomatic heart failure: randomized
   trial -- the Losartan Heart Failure Survival
                   Study ELITE II
  Bertram Pitt, Philip A Poole-Wilson, Robert Segal, Felipe A Martinez, Kenneth
 Dickstein, A John Camm, Marvin A Konstam, Gunter Riegger, George H Klinger,
James Neaton, Divakar Sharma, Balasamy Thiyagarajan on behalf of the ELITE II
                                   investigators

 Lancet 2000;355:1582-87
                          Background
48-week ELITE Study:
In 722 ACEI naïve elderly patients with heart failure due
to systolic left ventricular dysfunction comparing losartan
to captopril:
 •No difference in persistent rise in serum creatinine concentrations
 (primary endpoint)
 •46% reduction in all-cause mortality (17 vs 32 for losartan and
 captopril, respectively)
 •64% reduction in sudden death (5 vs 14 for losartan and captopril,
 respectively)
 •Similar improvement in functional status (NYHA, quality of life)
 •Superior tolerability with losartan
Lancet 2000;355:1582-87
                            ELITE II
                          Study Design
              > 60 yrs; NYHA II-IV; EF < 40%
   ACE I/AIIA naive or < 7 days in 3 months prior to entry
   Standard Rx (+ Dig/Diuretics ), B-Blocker stratification


        Captopril             Event Driven           Losartan
  50 mg 3 times daily          (Target 510           50 mg daily
       (N = 1574)                Deaths)             (N = 1578)
                           1.5 years follow-up

 Primary endpoint:            All Cause-Mortality
 Secondary endpoint:          Sudden Cardiac Death or
                              Resuscitated Arrest
 Other endpoints:             All-cause Mortality/Hospitalizations
                              Safety and Tolerability
Lancet 2000;355:1582-87
                                  ELITE II
                     Baseline Characteristics
                                     Losartan (n=1578)       Captopril (n=1575)

Age (mean, yrs)*                          71.4                         71.5
Gender (male/female %)                    70/30                        69/31
Ejection Fraction (mean %)                 31                           31
NYHA Funct. Class II/III/IV (%)          52/43/5                      52/43/5
Ischemic History (%)                       79                           79
Prior ACE Inhibitor                        23                           24
Beta Blocker (%)                           23                           21
Diuretic (%)                               77                           79
Cardiac Glycoside (%)                      50                           50
Analgesic/Salicylates (%)                  59                           59
*85% > 65 years of age                                   Lancet 2000;355:1582-87
                                                 ELITE II
                                    Primary Endpoint: All-Cause Mortality
                          1.0
Probability of Survival




                          0.8

                          0.6             Captopril
                                          Losartan

                          0.4
                                        Hazard Ratio (95-7% C.I.) = 1.13 (0.95-1.35) P = 0.16
                          0.2

                          0.0
                                0      100     200       300      400       500       600       700
                                                       Days of Follow-up
      Lancet 2000;355:1582-87
                                                   ELITE II
   Secondary Endpoint: Sudden Death / Resuscitated Arrest

                         1.0
Event-Free Probability




                         0.8
                                      Captopril
                         0.6          Losartan


                         0.4
                                    Hazard Ratio (95% C.I.) = 1.25 (0.98-1.50) P = 0.08
                         0.2

                         0.0
                               0   100      200       300      400       500       600    700
                                                    Days of Follow-up
     Lancet 2000;355:1582-87
                                                   ELITE II
                         Tertiary Endpoint: All-Cause Mortality / Hospitalization

                         1.0
Event-Free Probability




                         0.8

                         0.6
                                     Captopril
                                     Losartan
                         0.4
                                     Hazard Ratio (95% C.I.) = 1.07 (0.97-1.19) P = 0.18
                         0.2

                         0.0
                               0   100    200       300       400      500       600       700
                                                  Days of Follow-up
     Lancet 2000;355:1582-87
                                 ELITE II
                          Mortality by Subgroup
                                    Hazard Ratio of Death          Losartan Captopril Hazard
Subgroups at Baseline                   with 95% C.I.                 N       N        Ratio
       Age
          70                                                           901    913    1.05
          70                                                           677    661    1.33
       Gender
         Male                                                       1102       1083   1.12
         Female                                                      476        491   1.14
       NYHA Class.
         III/IV                                                         801    798    1.19
         II                                                             777    776    1.37
       % EF
         < 25                                                            267    290   1.00
         > 25                                                           1311   1284   1.19
       Beta Blockers
         With                                                        354        325   1.77
         Without                                                    1224       1249   1.05
         Overall                                                    1578       1574   1.13
                              0.6     0.8 1.0            2.0      3.0
                                        Hazard Ratio
                          Favors Losartan        Favors Captopril
Lancet 2000;355:1582-87
                                       ELITE II
Withdrawal for Adverse Experience (Excluding Death)
                20
                                                        Losartan (N=1578)
                                                        Captopril (N=1574)
                15    **
% of Patients




                                                   **   p0.001 between groups

                10
                                  **

                5
                                                  **

                0
                     Any AE   Drug-Related        Cough               HF
                                   AE
Lancet 2000;355:1582-87
                           ELITE II
                          Discussion
 • In controlled clinical trials involving about 5000 patients, of
   whom 2800 received losartan, acute and sustained
   hemodynamic benefits with chronic dosing have been seen,
   as well as effects similar to enalapril on exercise duration.
 • The ELITE II findings, together with previous experience in
   heart failure and the known pharmacology of losartan, make
   it probable that losartan resembles an ACE inhibitor in heart
   failure.
 • It still remains to be established, however, whether
   angiotensin II antagonists are a fully effective substitute for
   ACE inhibitors in heart failure.

Lancet 2000;355:1582-87
                           ELITE II
                          Discussion
• Losartan was not superior to captopril in improving
  survival in elderly heart-failure patients, but was
  significantly better tolerated.
• Based on extensive randomized, placebo-controlled
  observations, ACE inhibitors should be the initial
  treatment for heart failure, although angiotensin II
  receptor antagonists may be useful to block the
  renin angiotensin aldosterone system when ACE
  inhibitors are not tolerated.
Lancet 2000;355:1582-87

								
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