CONSENSUS Trial - Enalapril in Heart Failure (NYHA Class IV Patients')

BRIEF SUMMARY

Name: CONSENSUS

Specialty: Cardiology, Congestive Heart Failure (CHF). 

Problem: Heart failure ( All Symptomatic - NYHA Class IV)

Population: 253 patients. (126 placebo and 127 Enalapril)

Inclusion criteria:
Patients with severe congestive heart failure (New York Heart Association [NYHA] functional class IV)
Exclusion criteria:
Acute pulmonary edema
Hemodynamically important aortic or mitral-valve stenosis
Myocardial infarction within the previous two months
Unstable angina
Planned cardiac surgery
Right heart failure due to pulmonary disease
Serum creatinine concentration above 300 μmol per liter.
Intervention: Enalapril
Control: Placebo
Follow-up: Median 188 days (1 day to 20 months range)
Primary endpoint:
Six-month mortality
Cause of death Secondary endpoint(s):
12-month and overall mortality during the entire trial period, according to the "intention-to-treat" principle.
Brief Results:

Crude mortality was 40% less in Enalapril group. (26 percent with Enalapril versus 44 percent in placebo).
Effective reduction in mortality at the end of the study 27 percent.
Total reduction of mortality in patients' with PROGRESSIVE heart failure = 50%.
No change in sudden cardiac death.

Link to Original Paper

Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study

4 Jun 1987 N Engl J Med. 1987 Jun 4;316(23):1429-35.:Reductions in
-All-cause mortality
-NYHA classification
-CHF progression
No reduction in sudden cardiac death

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FURTHER DETAILS:

Seems like all cardiology trials have these catchy names. So what does CONSENSUS Stand for?

COoperative North Scandinavian ENalapril SUrvival Study.

What is so special about this trial?

This was one of the first trials showing improvement in survival (mortality benefit) of heart failure patients who were started on ACE inhibitor. (enalapril in this instant)

What is this trial all about?

This trial looked at use of ACEI enalapril at doses between 2.5 mg to 40 mg daily in NYHA class IV heart failure and any associated changes in the prognosis in NYHA class IV congestive heart failure.

What was the trial design?

Trial compared Enalapril (126) to Placebo (127) in 253 patients. Patients were also continue on standard medication for heart failure at that time which included mainly vasodilators at that time.

What were the main findings?

Follow-up averaged 188 days (range, 1 day to 20 months).

The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group — a reduction of 40 percent (P = 0.002).

Mortality was reduced by 31 percent at one year (P = 0.001).

By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group — a reduction of 27 percent (P = 0.003).

The entire reduction in total mortality was found to be among patients with progressive heart failure (a reduction of 50 percent), whereas no difference was seen in the incidence of sudden cardiac death.

Were there any specific advantages observed in using Enelapril?

Yes, a significant improvement in NYHA classification was observed in the enalapril group, together with a reduction in heart size and a reduced requirement for other medication for heart failure.

Were there any specific side effects of Enalapril which limited the drug from reaching its full potential?

Hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group. After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients, this side effect was less frequent.

Where and when was this trial published? and how can I obtain a copy of official pdf?

here is the link - NEJM, N Engl J Med 1987; 316:1429-1435CONSENSUS TRIAL CLICK HERE

Anything else I need to know?

Well unlike popular belief most patients were from Finland, Norway and Sweden (mostly caucasians and hardly any African Americans) none from USA!?.

Tell me more?

Well many of the patients' were on ISDN (isosorbide dinitrate), hydralazine and prazosin and the trial even recommended these drugs in people who worsened despite enalapril!!!.

And how did people on vasodilator therapy do?

Well simple answer will be not sure, but look at the second graph below people on enalapril who were NOT on vasodilators actually did worse. So retrospectively we can conclude that vasodilators did have at least some mortality benefit along with enalapril.

Here are the graphs from the trial:

 So here you go no need to read the entire article, we have summarized the entire trial for you right here at cardiologytrials.blogspot.com.

We shall also add a table with all the relevant trials in every section of this blog.