ALBATROSS: Aldersterone Blockade Fails to Improve Outcomes in Acute MI

LONDON, England—Patients with acute MI but not heart failure derive no protection against adverse events from aldersterone antagonists, according to data from the ALBATROSS trial presented August 30, 2015, at the European Society of Cardiology Congress.

However, the study did observe a significant reduction in the risk of death for STEMI patients. “It is an intriguing, hypothesis-generating finding which needs to be examined further in adequately-sized trials specifically dedicated to STEMI patients,” said principal investigator, Gilles Montalescot, MD, PhD, of Centre Hospitalier Universitaire Pitié-Salpêtrière (Paris, France), in a press release.

ALBATROSS randomized 1,622 acute MI patients within 72 hours of symptom onset to receive standard therapy alone (n = 801) or with aldersterone blockade (n = 802) consisting of a 200-mg IV bolus dose of potassium canrenoate followed by a 25-mg oral dose of spironolactone within 12 to 24 hours that was continued daily for 6 months. Median follow-up was 118 days.

Three-quarters of patients presented with STEMI, and 1% had prior heart failure.

Results No Better Than Control

At 6 months, the composite of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, and new/worsening heart failure (primary endpoint) occurred at similar risk for patients who received aldersterone blockade and those who did not (HR 0.97; 95% CI 0.73-1.28). Other secondary endpoints also were equivalent, though the rate of hyperkalemia > 5.5 mmol/L^-1 was higher in the blockade group (table 1).

Prespecified subgroup analysis consistently showed no survival benefit. A notable exception was STEMI patients, who were less likely to die after receiving aldersterone blockade vs standard therapy (HR 0.20; 95% CI 0.06-0.69; P = .0044).

No Immediate Clinical Applications

“Aldersterone is a stress hormone that is acutely released in acute myocardial infarction. This hormone has deleterious cardiovascular effects, leading to cardiac arrhythmia, cardiac ischemia, heart failure, and sudden death,” Dr. Montalescot explained.

The ALBATROSS findings, he said, are in contrast to those of other studies including the EPHESUS trial, which demonstrated in 2003 that patients experiencing heart failure after acute MI have reduced mortality risk when they receive the aldersterone antagonist eplerenone.  

ALBATROSS “failed to show a benefit of aldosterone blockade initiated early in MI, when heart failure [was generally] not present,” Dr. Montalescot said, acknowledging that the trial was underpowered due to fewer than expected adverse events. Yet it still “highlights the relative safety of the aldosterone blockade used in the study,” he added.  

Although research on the STEMI subgroup may prove fruitful, for now “the results of the ALBATROSS study do not warrant the extension of aldosterone blockade to MI patients without heart failure,” Dr. Montalescot concluded.  

Discussant John McMurray, MD, of the University of Glasgow (Glasgow, Scotland), praised the researchers for conducting an investigator-initiated trial that was entirely funded by the French Ministry of Health. But limitations to the ALBATROSS study design, and its subsequent lack of statistical power, mean that “we cannot draw any definite conclusions about the effect of [aldersterone antagonists]” in acute MI patients without heart failure.

The STEMI subgroup analysis, while interesting, is “unreliable,” Dr. McMurray cautioned.  

Roxana Mehran, MD, of Mount Sinai Medical Hospital (New York, NY), agreed with Dr. Montalescot that further study focusing on STEMI is justified. “While the trial was underpowered, as rightly presented by investigators, I do think that a follow-up trial to evaluate this in larger cohort of STEMI patients would be warranted,” she told TCTMD in an email. “STEMI patients are at high risk of mortality, and if this is effective, it would be a step forward.”

Source: 
Montalescot G. Early aldersterone blockade in acute myocardial infarction: the randomized ALBATROSS trial. Presented at: European Society of Cardiology Congress; August 30, 2015; London, England.

Disclosure:  

• Dr. Montalescot reports receiving research grants to his institution and consulting/lecture fees from several drug and device companies.

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