A Medical Device Daily

Results from the IRIS (Immediate Risk Stratification Improves Survival) clinical trial, supported in part by Medtronic (Minneapolis) were presented this week at the Annual Scientific Session of the American College of Cardiology (ACC; Washington).

The results showed that sudden cardiac death in a specific subset of immediate post-myocardial infarction (MI) patients was statistically significantly reduced with implantable cardioverter-defibrillator (ICD) therapy. However, in this narrowly defined patient population, ICDs did not reduce mortality from all causes, as all causes are not treatable by ICDs, Medtronic said.

ICDs are 98% effective at terminating the dangerous heart rhythms that can lead to sudden cardiac death, but are not currently indicated for use in immediate post-MI patients. The IRIS trial sought to determine if survival amongst a subset of post-MI patients who were at high risk for sudden cardiac death could be improved by ICD therapy received in the first 31 days after a heart attack.

The trial compared outcomes for patients who received an ICD within a month of a heart attack to patients treated with standard medical therapy alone.

There were fewer sudden cardiac deaths in patients who got an ICD in the days following a heart attack, but that was counterbalanced by an increase in non-sudden cardiac deaths, according to authors of the study.

"Based on these findings, routine ICD implantation after [heart attack] cannot be recommended at this time," study author Dr. Adnan Chhatriwalla of the Cleveland Clinic said in a summary of the trial.

Patients who received an ICD in the Iris study were at high risk for sudden cardiac death, which can result from the onset of an abnormal heart rhythm. But the results for about 900 patients treated in European hospitals found no difference in the primary endpoint of all-cause mortality between groups at three years.

A significant percentage of people who survive a heart attack will ultimately die from a dangerous heart rhythm originating in the lower chambers of the heart, Medtronic said. About 15% will die in the first weeks, and an additional 10% during the first year.

"Medtronic is committed to developing an evolving base of clinical evidence critical to scientific advancement and medical practice," said David Steinhaus, MD, medical director of the Cardiac Rhythm Disease Management business at Medtronic. "The IRIS trial is another example of our efforts to identify the patients who will benefit most from our life-saving and life-improving therapies."

The company noted that the IRIS results do not conflict with previous data that informed current evidence-based treatment guidelines which showed that use of ICDs in a more broadly defined range of post-MI patients (those who received ICD therapy at least 40 days after experiencing a heart attack) reduced all-cause mortality by 31%. Current medical guidelines recommend ICD therapy for post-MI patients with an ejection fraction a common measure of the heart's pumping function of 35% and below, and after at least 40 days have passed since their heart attack.

In other ACC news:

• Impulse Dynamics reported findings from the FIX-HF-5 study of its Optimizer system.

The company noted that previous studies have demonstrated safety and efficacy of the Optimizer system's cardiac contractility modulation (CCM) signals when applied for three months. The FIX-HF-5 study was designed to test the longer-term effects in the largest randomized study to date.

CCM therapy is a new treatment for patients with heart failure. Unlike electrical signals delivered by other cardiac devices, such as pacemakers and implantable defibrillators, CCM signals do not initiate a heartbeat. Rather, CCM signals are intended to modify heart cell function in a manner that improves the strength of the heart muscle, therefore potentially enhancing the heart's overall pumping ability. CCM is designed to increase the forcefulness of the heart's pumping action rather than initiating a new contraction.

The study met its primary safety endpoint, which was a noninferiority demonstration of the composite of all-cause mortality and all-cause hospitalizations. In terms of efficacy, the results showed that, compared to the control group, patients treated with CCM signals over the other group had significantly improved exercise tolerance as judged by an increase in peak oxygen update (p=0.02) and an improvement in quality of life as judged by a reduction in the Minnesota Living with Heart Failure score (p<0.0001).

The results did not, however, meet the study's overall primary efficacy endpoint demonstrating improvement in ventilatory anaerobic threshold, though that endpoint was met in a less sick subgroup of the patients.

"We are pleased to report these longer term data that add to the growing wealth of knowledge showing the potential of CCM as a therapy for heart failure patients with no other options," said William Abraham, MD, professor of internal medicine and director of the Division of Cardiovascular Medicine, Ohio State University Medical Center (Columbus).

• In a subgroup representing the less sick half of the study population (NYHA Class III with ejection fraction 25% and above), the study found even greater improvements not only in peak VO² (p=0.001) and quality of life (p=0.003), but also in the primary endpoint of ventilatory anaerobic threshold (p=0.03). These effects were largely maintained at twelve months as well.

"This subgroup of the less severely impaired patients appeared to demonstrate an overall greater response rate that those in the control group," noted Dr. Alan Kadish, professor, Division of Cardiology, Feinberg School of Medicine, Northwestern University (Chicago). "We are particularly encouraged by the findings in this subgroup of patients and look forward to focusing on this subgroup in our next study."

The Optimizer is CE marked and commercially available in Europe.

• Atherotech (Birmingham, Alabama), developer of the VAP Cholesterol Test, reported the addition of new cardiovascular and metabolic testing panels. Atherotech said it is adding more than a dozen new tests, including C-Reactive Protein (hsCRP), ApoE genotype, and NT-proBNP, for assessment of patients at intermediate to high risk of cardiometabolic diseases. The company is also adding advanced and follow-up cardiovascular disease (CVD) risk profiles.

"We're maximizing the value of our core VAP technology with additional cardiometabolic tests," said Atherotech President Michael Mullen. "This provides physicians and cardiology practices with a single source for the VAP Cholesterol Test plus the new test panels. You get the complete cardiovascular and metabolic view."

The VAP Test, which recently added apoAI (and the apoB/apoAI ratio) to its panel, uses advanced lipid profile testing in the identification of individuals at increased risk of heart disease. The company said the new test panels enable Atherotech to increase its scientific and diagnostic capabilities by offering much more complete cardiometabolic testing.

The new test panels are available immediately and also include homocysteine, creatinine, creatine kinase (CK), HbA1c, TSH, ALT, AST, urea nitrogen (BUN), glucose, vitamin D, fibrinogen and insulin. The tests can be ordered individually, or bundled as part of a custom risk profile that may also include the VAP Test.