麻豆传媒

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PARIS -- The DAPA trial suggested that certain ST-elevation myocardial infarction (STEMI) survivors may benefit from prophylactic implantable cardioverter-defibrillator (ICD) use after primary percutaneous coronary intervention (PCI), but several issues with the study preclude this from being conclusive.

A survival advantage was observed for high-risk people randomized to ICD implantation, as this group had a 24.4% rate of all-cause mortality over a median of 9 years (compared with 35.5% for controls getting medications only; HR 0.58, 95% CI 0.37-0.91), Danielle Haanschoten, MD, of Isala Hospital in Zwolle, the Netherlands, told the audience at the European Society of Cardiology congress here.

Such a benefit was driven by a lower cumulative risk of cardiac death (11.5% vs 18.5%, HR 0.52, 95% CI 0.28-0.99), which was further broken down into numerical reductions in heart failure deaths (8.4% vs 12.6%) and sudden cardiac death (SCD) or arrhythmic deaths (3.1% vs 5.9%).

Notably, however, DAPA was started in 2004 and terminated prematurely in 2013 due to very slow accrual. The original power calculation suggested that 700 patients would be needed to tie ICD therapy to a mortality benefit -- in the end, Haanschoten's group enrolled just 266 people from 12 centers in the Netherlands and Poland.

Enrollment problems may be partly attributed to the publication of negative trials and around that time, said co-investigator Arif Elvan, MD, PhD, also of Isala Hospital, at a press conference.

Another problem with DAPA was that ICD therapy was not defined as a secondary endpoint at the time of trial design. Consequently, it is difficult to say whether the survival benefit observed stems from ICDs firing early on or years later.

"Premature termination of the trial and lack of ICD therapy data limits the interpretation of the results," Haanschoten admitted. She added that by 2013, the control group had crossed over to ICD therapy at a 19.3% rate (vs 6.1% crossover from ICD to controls).

Nevertheless, early prophylactic ICD implantation may be considered for some high-risk patients, Elvan concluded.

This conclusion is not substantiated by the data, but it is already known that ICD is beneficial in post-MI PCI patients beyond 40 days if left ventricular ejection fraction (LVEF) remains low, commented Stefan Kääb, MD, PhD, of Ludwig-Maximilians University Hospital Grosshadern in Munich, Germany, who was not involved with the study.

Indeed, European and U.S. guidelines both give class 1A recommendations for ICD therapy at least 6 weeks after MI in heart failure patients if LVEF is 35% or below, according to session discussant Christophe Leclercq, of Centre Cardio-Pneumologique in Rennes, France.

Problems of DAPA aside, there are several other issues that suggest it may be time to revisit the benefit of ICDs for primary prevention in post-MI patients, Leclercq said.

First, everything is based on LVEF, which is known to be difficult to measure with echocardiography. Second, rates of SCD in heart failure have dropped over time, he told the audience.

Average age in DAPA was 60 years; just under 80% of the group were men. The majority had very large anterior infarctions, with peak creatinine kinase exceeding 5,000 U/L in both the ICD and control groups.

Randomization to or medications alone took place 30-60 days after the index STEMI (median 50 days). A single-chamber device was implanted in 82.4% of the ICD group.

Patients were eligible if they had undergone PCI for STEMI and were subsequently deemed high-risk, mostly due to an LVEF under 30% within 4 days, and less frequently so because of thrombolysis in MI flow under 3 after PCI, primary ventricular fibrillation, or a Killip 2+ classification.

The latter three categories for "high-risk PCI patients" are not well established and have not been prospectively tested, Kääb cautioned.

There were no deaths, but there were a few complications from ICD surgery: pocket bleeding (1.5%), local pocket infection (2.3%), and pneumothorax (0.8%).

At 18 months, LVEF was re-assessed with transthoracic echocardiography. The two arms were roughly split between those who had LVEF improve by at least 10% and those whose LVEF was unchanged (with a small minority exhibiting reverse remodeling).

ICDs were not tied to a survival benefit among the 110 DAPA participants who had LVEF exceed 30% by then (HR 0.47, 95% CI 0.12-1.90).

"More sophisticated risk stratification tools are needed to identify patients at high risk of SCD early after STEMI," Haanschoten said.

To that end, investigators from multiple sites are collaborating on PROFID, a "huge project" where data from one million patients are being pooled to create a risk score for SCD after MI, according to Leclercq.