Why is this trial a landmark trial: Just like the RALES trial showed effectiveness of aldosterone receptor blockade in both ischemic and non-ischemic heart failure. EPHESUS trial showed efficacy of Eplerenone (selective cousin of spironolactone) in post-MI HF.
What was not good about this trial: I think investigators limited themselves to post-MI heart failure, if they had included non-ischemic patients as well then they would have had much larger market for Eplerenone. (now Eplerenone use is pretty much limited to post-MI HF and CHF with intolerant SE's to Spironolactone).
The fact that Eplerenone showed only 15% RRR in all cause mortality (half of spironolactone) also made clinicians a bit jittery in using Eplerenone as first choice instead of Spironolactone.
They also had tough time proving efficacy of Eplerenone because of more than 75% participants were on beta blockers which may have knocked down the true efficacy of the Eplerenone when compared to Spironolactone in RALES trial. (remember in RALES trial only 10% participants were on beta-blockers, and also RALES recruits had average EF of 25% where as in EPHESUS average EF was much higher - so it may be easier to prove improvement of EF from 25% to 45% THAN to prove improvement from 40% to 45%).
Specialty: cardiology,CHF
Problem: LV dysfunction post-MI (ischemic HF or ischemic cardiomyopathy with EF < 40%)
Population: 6452 patients
Inclusion criteria:
Patients in whom the following criteria were met were eligible for randomization 3 to 14 days after acute myocardial infarction:
Acute myocardial infarction as documented according to standard criteria
Left ventricular dysfunction as documented by a left ventricular ejection fraction of 40 percent or lower on echocardiography, radionuclide angiography, or angiography of the left ventricle after the index acute myocardial infarction and before randomization
Heart failure as documented by the presence of pulmonary rales, chest radiography showing pulmonary venous congestion, or the presence of a third heart sound.
In patients with diabetes who met the criteria for left ventricular dysfunction after acute myocardial infarction, symptoms of heart failure did not have to be demonstrated, since such patients have an increased risk of cardiovascular events similar to that of nondiabetic patients with symptoms of heart failure.
Exclusion criteria:
Use of potassium-sparing diuretics
Serum creatinine concentration of more than 2.5 mg per deciliter (220 μmol per liter)
Serum potassium concentration of more than 5.0 mmol per liter before randomization
Intervention: Eplerenone
Control: Placebo
Follow-up: Mean 16 months
Primary endpoint:
Time to death from any cause
Time to death from cardiovascular causes or first hospitalization for a cardiovascular event, including heart failure, recurrent acute myocardial infarction, stroke, or ventricular arrhythmia
Secondary endpoint(s):
Death from cardiovascular causes and death from any cause or any hospitalization
Details:
Patients received optimal medical therapy, which could include ACE inhibitors, angiotensin-receptor blockers, diuretics, and beta-blockers, as well as coronary reperfusion therapy.
Results:
-15% RRR in deaths (versus 30% RRR in RALES with Spironolactone)
-16% RRR in CV death or hospitalization for CV events
-8% RRR in death from any cause or any hospitalization
-21% RRR in sudden death from cardiac causes
-Increased risk of serious hyperkalaemia
Original Paper - Link
Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction
3 Apr 2003 N Engl J Med. 2003 Apr 3;348(14):1309-21.: CLICK HERE FOR NEJM LINKPUBMED LINK CLICK HERE
Eplerenone vs. placebo
SUMMARY TRIAL:
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