Vienna, Austria - New real-world data from a prospective study designed to assess the incidence of implantable cardioverter defibrillator (ICD) interventions in patients treated with the device following MI has shown the incidence of appropriate and inappropriate shocks to be nearly identical to the incidence observed in a clinical trial where benefit was first observed [1].

Dr Guiseppe Boriani

Presenting the results of the Survey to Evaluate Arrhythmia Rate in So-Called High-Risk Myocardial Infarction (SEARCH-MI) here at the European Society of Cardiology Congress 2007, investigators showed that the number of patients who received an appropriate shock was equivalent to that observed in the Multicenter Automatic Defibrillator Implantation Trial (MADIT-2) and suggest that the evidence of benefit of ICD therapy in post-MI primary-prevention patients can be replicated in routine clinical practice.

"I think it is quite important to have information—the MADIT-II data are related to patients included in the clinical trial—showing that the benefit can be translated into daily clinical practice, where the patients are different, often more compromised, with more comorbidities," lead investigator Dr Guiseppe Boriani (University of Bologna, Italy) told heartwire. "When we're looking at clinical trials, they are a select group of patients, the very sick are excluded, so it's important if a healthcare system has to pay for treatment that we know the efficacy of trials translates into effectiveness in clinical practice."

The MADIT-2 study

MADIT-2, first presented in 2002 at the American College of Cardiology Scientific Sessions, in Atlanta, GA and reported by heartwire at that time, confirmed a survival benefit from ICD implantation in a vastly enlarged group of patients, those with any history of MI and left ventricular dysfunction with an ejection fraction (EF) of 30% or less. The results led to the amendment of US and European guidelines for the clinical management of patients at risk for sudden death, leading to the recommendation of ICDs for prophylactic indications in MADIT-2-type patients. While the MADIT-2 data were solid, Boriani told heartwire it was still unknown whether the benefit observed in that trial would translate to patients in clinical practice.

The aim of the SEARCH-MI registry, established in 2002, was to prospectively evaluate the arrhythmic rate and ICD interventions in patients at high risk for life-threatening ventricular arrhythmias. In Italy, Germany, Austria, Israel, and Saudi Arabia, 69 centers participated in the registry, with 788 post-MI patients admitted for an ICD indication as primary prevention (the present analysis included 556 patients treated for at least 70 days). The patients included in the registry were typically sicker, having decreased exercise capacity compared with the MADIT-2 patients, more left bundle branch block, less previous CABG surgery, and worse heart failure as measured by NYHA class. In addition, more SEARCH-MI patients were treated with diuretics, amiodarone, and beta blockers.

Despite the patients being "more compromised," Boriani said the device functioned appropriately, on a level equivalent to that observed in the landmark trial. At one year, 18% of patients in the SEARCH-MI registry had an arrhythmic event appropriately terminated, compared with 17% of MADIT-2 patients. At two years, the results were similar, with 26% of SEARCH-MI patients and 27% of MADIT-2 patients having had an arrhythmic event terminated by the ICD. There was no difference in overall mortality or sudden cardiac death at one and two years.

CRT being used more frequently

The investigators said the registry also highlights the changing trends in device therapy for heart-failure patients. Approximately 25% of patients in the SEARCH-MI registry received a device for cardiac resynchronization therapy (CRT).

"The data that we saw a few years back with the landmark trials, such as CARE-HF and COMPANION, are now starting to be implemented into daily clinical practice," Boriani told heartwire. "Today, preventing sudden death in patients with left ventricular dysfunction implies the use of both ICDs and devices that provide ICD and CRT capabilities. Still, these are just a minority of patients, about one in four in this study, but it might be as high as 30%."

During a morning press conference announcing the results, Boriani said the patients did not undergo T-wave alternans (TWA) testing, a test that has been proposed by policy-makers and some clinicians as a way to stratify patients who would benefit most from ICD therapy. Speaking during the late-breaking clinical-trials session, Dr Gunther Breithardt (University of Münster, Germany), who commented on the results of SEARCH-MI, praised the study investigators for the real-world data. However, he noted that there is a great deal of diversity in implementing the guidelines across Europe and that this particularly registry was heavily skewed toward enrolling Italian patients, and to a lesser extent, Germans.

Still, in discussing the benefits of registries and clinical trials, Breithardt said the registries allow for the assessment of results in clinical reality. In that vein, he said the SEARCH-MI study allows doctors to be confident of MADIT-2 findings in a heterogeneous patient population.