# Presentation: 711018

## Adverse CV Events (Frequency ≥ 1.5%) in Either Treatment Group (Uptitration Phase)

- CAPRICORN

***Adverse CV Events (Frequency ≥ 1.5%) in ******Either Treatment Group (Uptitration Phase)***

## COPERNICUS

**All-Cause Mortality**

**% Survival**

**Carvedilol**

**Placebo**

**0**

**3**

**6**

**9**

**12**

**15**

**18**

**21**

**Months**

**100**

**90**

**80**

**60**

**70**

** ****0**

- Packer M., et al. *N Engl J Med.* 2001;344:1651–1658.

**35% ******** in risk**
***P*****=.00013 (unadjusted)*****P*****=.0014 (adjusted)**

## Effect of Study Drug on Duration of Index Hospitalization

- CAPRICORN

***Effect of Study Drug on ******Duration of Index Hospitalization***

## DSMB Meeting #5 (March 10, 1999)

- Closed Section
- • 	“The best option was thought to be a change of the primary endpoint to Death or cardiovascular hospitalization, keeping the target number of events for the primary endpoint unchanged.  This would substantially increase the event rate and would allow the study to be completed in good order.  Professor Julian was asked to write to the Steering Committee with this proposal.”
- • 	Despite change in primary endpoint, stopping rules were still to be based on all-cause mortality.

- CAPRICORN

***DSMB Meeting #5 (March 10, 1999)***

## Why Was Cardiovascular Hospitalization Defined To Include All Such Events?

- • 	Original protocol paid little attention to definition of CV hospitalization because it was a secondary endpoint.  Steering Committee assigned responsibility for defining CV hospitalization to Endpoint Committee.
- • 	Endpoint Committee defined CV hospitalization as hospitalizations for which there was no clear non-CV cause.  Committee did not target reasons that might be favorably influenced by -blockade.
- • 	Steering Committee was reluctant to make too many changes.  When it changed the primary endpoint (by simply elevating a secondary endpoint), it was reluctant to change the definition of the endpoint.

***Why Was Cardiovascular Hospitalization Defined To Include All Such Events?***

## Reasons for Other CV Hospitalization

- CAPRICORN

## Effect of Carvedilol on Primary Endpoints According to Prior Use of b-Blockers

**Effect of Carvedilol on Primary Endpoints According to Prior Use of b-Blockers**

- CAPRICORN

- Number in brackets under each hazard ratio denotes number of events

## Total Number of Hospitalizations for Specified Reasons

- CAPRICORN

- Hospitalizations with more than one cause were counted only once and attributed to the worst event listed as a reason for the admission (myocardial infarction > heart failure > unstable angina > stroke > TIA > other angina or chest pain > nonclassified or other > cardiovascular procedure > noncardiovascular).

***Total Number of Hospitalizations for Specified Reasons***

## All-Cause Mortality

**0.7**

**0.8**

**0.9**

**1.0**

**0**

**0.5**

**1.0**

**1.5**

**2.0**

**2.5**

**Carvedilol**

**Placebo**

**Years**

**Proportion Event Free**

*The CAPRICORN Investigators, Lancet 2001*

- P=0.031

***All-Cause Mortality***

- CAPRICORN

## Effect on Cardiovascular Endpoints

- CAPRICORN

## All-Cause Mortality Subgroups

- Age ≥ 70 (n=618)

- Men (n=1440)
- Women (n=519)

- Russia (n=600)
- Ex-Russia (n=1359)

- Prior MI (n=589)
- No prior MI  (n=1370)

- Anterior MI (n=1108)
- Inferior MI  (n=410)
- Other MI (n=441)

- Thrombolytic (n=718)
- No thrombolytic (n=1241)

- PTCA for MI (n=243)
- No PTCA for MI (n=1716)

**Hazard Ratio**

**0.4**

**0.7**

**1.0**

**1.3**

- Current/prior CHF (n=936)
- No current/prior CHF (n=1023)

- Diuretics during MI (n=658)
- No diuretics during MI (n=1301)

- Angina (n=1090)
- No angina (n=869)

- Hypertension (n=1055)
- No hypertension (n=904)

- Diabetes (n=437)
- No diabetes (n=1522)

- Heart rate < 70 (n=590)
- Heart rate > 70 (n=1365)

**Hazard Ratio**

**0.4**

**0.7**

**1.0**

**1.3**

***All-Cause Mortality Subgroups***

- CAPRICORN

## CAPRICORN Subgroups

***CAPRICORN Subgroups***

## Effect on Recurrent Infarction

***Effect on Recurrent Infarction***

- CAPRICORN

- Among first events leading to death or CV hospitalization (co-primary endpoint), 45 of such events on placebo and 27 such events on carvedilol were due to a recurrent infarction.
- Total number of hospitalizations for myocardial infarction (including first and recurrent) was 60 in the placebo group and 37 in the carvedilol group.