• Cardiology Clinical Trials
• Interventional Techniques & Devices
• Myocardial Infarction

The Immediate Risk Stratification Improves Survival (IRIS) trial compared the safety and efficacy of the early insertion of an implantable cardiac defibrillator (ICD) or medical treatment alone in 898 patients who were at high risk for sudden cardiac death (SCD) after myocardial infarction (MI). The primary analysis of the IRIS trial showed significantly fewer deaths due to SCD in the ICD group compared with medical therapy alone (27 vs 60 deaths; p=0.049). However, this was offset by an increase in non-SCD (68 vs 39 deaths; p=0.001), resulting in a neutral effect on total mortality after 72 months (HR, 1.04; p=0.76) [Steinbeck G et al. New Engl J Med 2009].

Gerhard Steinbeck, MD, University of Munich, Munich, Germany, presented results from an exploratory post hoc analysis of the IRIS trial, designed to elucidate predictors and mechanisms that contribute to the observed increase in non-SCD in the ICD group.

In the current analysis, investigators applied different statistical tools—the kernel method for smoothed hazard curve estimation—to examine daily mortality risk over time. They found that ICD use decreased the risk for SCD but only within the first 2 years following implantation. Conversely, ICD use was associated with a steady increase in the risk of non-SCD after implantation, particularly after 3 years of follow-up.

In a multivariate analysis, mortality risk patterns were consistent across 30 subgroups, with early ICD associated with decreased risk of SCD and increased risk of non-SCD in each subgroup, except for a small group of 91 patients with STEMI who did not undergo reperfusion (interaction p<0.001). Further prospective data are needed to better understand this observation in a small subgroup whose characteristics may differ from the overall cohort.

Independent of ICD use, five factors predicted total mortality: older age (HR, 1.49; p<0.001), left main or three-vessel disease (HR, 1.48; p=0.004), QRS ≥120 ms (HR, 1.60; p=0.001), New York Heart Association class 3 or 4 heart failure (HR, 2.00; p<0.001), and ejection fraction <35% (HR, 2.18; p<0.001). Conversely, use of an angiotensin receptor-converting inhibitor or angiotensin receptor blocker (HR, 0.56; p=0.003) and administration of clopidogrel (HR, 0.64; p=0.001) are associated with lower mortality risk.

Right ventricular pacing was associated with increased total mortality (HR, 2.1; p<0.001) due to an elevated risk of non-SCD (HR, 3.8; p<0.001). Periods of appropriate or inappropriate shocks were associated with a particularly high risk of total mortality (HR, 4.7; p<0.001) due to increased non-SCD (HR, 9.9; p<0.001).

Current guidelines for primary prevention exclude ICD implantation in patients within the first 40 days after MI. However, this restriction excludes a vulnerable population, given that the SCD is significantly higher immediately post-MI, especially in patients with low left ventricular ejection fraction.

Discussant Christophe Leclercq, MD, Rennes University Hospital, Rennes, France, said that the new IRIS analysis did not answer the question of why ICD fails to reduce total mortality early after MI. As such, there is no evidence to support changes to the current guidelines for ICD implantation, he concluded.

• © 2011 MD Conference Express