ACC.08 Late Breaking Clinical Trials Document Advancements in Medical Device Research, Underscore Medtronic Leadership in Clinical Evidence

Appropriate Device Use in At-Risk Patients Among Focus of Ongoing and Future Clinical Trials

As ACC.08, the annual congress of the American College of Cardiology nears its close, Medtronic Inc. (NYSE: MDT) reaffirms its commitment to clinical evidence supporting the full range of implantable cardiac device therapy as standard of care for patients with heart failure, arrhythmias and those at risk of sudden cardiac arrest (SCA). As evidenced by today’s Late Breaking Scientific Sessions on three Medtronic-sponsored clinical trials, and poster data presented earlier in the congress, Medtronic continues to advance clinical science that impacts medical practice worldwide.

“Our investment in clinical research – measured by both the size and scope of trials in which we’re involved worldwide – is unsurpassed in the cardiac device industry,” said David M. Steinhaus, M.D., vice president and medical director of the Cardiac Rhythm Disease Management business at Medtronic. “This commitment is critical to scientific and medical advancement and is another way in which we provide greater access to life-saving and life-improving therapies.”

Medtronic’s continued study of certain cardiac tests and risk markers seeks to better identify and treat patients at risk for SCA. The company will soon announce details of several major clinical trials, including VEST / PREDICTS (The Vest Prevention of Early Sudden Death Trial / The Prediction of ICD Therapies Study), a study designed to develop and validate a tool that predicts which post-MI (myocardial infarction, or heart attack) patients are at greatest risk of SCA. These initiatives are part of a National Institutes of Health (NIH) grant awarded to the University of California-San Francisco (UCSF) and are co-funded by several industry partners.

Three Medtronic-sponsored studies were presented today at ACC.08 Late Breaking Clinical Trials:

* CARISMA (Cardiac Arrhythmias and Risk Stratification after Myocardial Infarction) showed that many arrhythmias are predictors of cardiac death for up to two years from the acute phase in post-MI patients with ejection fraction (EF) – a measure of the heart’s pumping ability – of ≤40 percent. Devices such as the Medtronic Reveal® Plus insertable loop recorder (ILR) and Reveal® DX, the company’s newest insertable cardiac monitor (ICM), can monitor asymptomatic arrhythmias and can be appropriate patient management tools for assessing post-MI patients who may benefit from drug or device (pacemaker or ICD) therapy.
* It’s known that patients with sustained atrial fibrillation (AF) are at increased risk of stroke. To further advance evidence on stroke, Medtronic sponsored the TRENDS trial, which looked at thromboembolic events, or TE (ischemic stroke, transient ischemic attack [TIA], or non-stroke systemic embolism), in patients with implanted cardiac devices using Medtronic’s Cardiac Compass® Reports. Providing up to 14 months of clinical data, the reports show tracked arrhythmia episodes, therapies delivered, physical activity, heart rate, and other device and physiologic data. The TE rate in the study was low compared to past pharmacological trials of stroke. This prevented analysis of the primary objective of the study, whether AT/AF burden over 30 days is an independent predictor of thromboembolic events in subjects not receiving anticoagulation therapy. Nonetheless, the results from post-hoc analysis suggest that AT/AF burden, as reported by Cardiac Compass Reports, of 5.5 hours on any day during the preceding 30 days may double the risk for TE, independent of known risk factors and antithrombotic therapy.
* REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) was the first large-scale, global, randomized, double-blind trial to evaluate cardiac resynchronization therapy (CRT) in asymptomatic or mildly symptomatic heart failure patients (NYHA Class I, II). Despite the trial not meeting statistical significance for the pre-specified analysis of its primary endpoint of a heart failure Clinical Composite Score at 12 months, more patients in the trial improved with CRT. The Clinical Composite Score is a measure of both subjective and objective assessments. Additionally, in a secondary endpoint, the trial showed that CRT leads to improvement in cardiac structure and function as measured by echocardiography, meaning the heart size is reduced and therefore acts as a more-efficient pump.

“I believe this data indicates that in this study, CRT in combination with optimal medical therapy improved left ventricular function in this population of heart failure patients,” said Dr. Cecilia Linde of Karolinska University Hospital, Stockholm, Sweden, worldwide principle investigator for the REVERSE trial. “Another observation is that over the 12-month follow-up period, CRT in mildly symptomatic patients delayed the time to first heart failure hospitalization.”

Also presented at ACC.08 earlier this week were results from the MASTER II (Microvolt T Wave Alternans Testing for Risk Stratification of Post MI Patients) trial, which concluded that MTWA test result does not significantly discriminate risk of life-threatening ventricular tachyarrthythmic events (LTVTE) in patients with a previous MI and left ventricular (LV) EF between 31-40 percent, although the incidence of LTVTEs in community practice was low. Further, a second poster from the MASTER trial titled, “Evaluation of MTWA test result concordance over time in the MASTER trial,” explored how MTWA test results change over time. Essentially, year-to-year changes in MTWA test results are common in patients with ischemic LV dysfunction, which has important implications for patient testing.

“Each step we take with clinical research advances science and the base of evidence regarding the safety and efficacy of device therapy,” Steinhaus added. “Though every trial may not achieve statistically significant results, what we learn from the process and findings contribute to new scientific understanding. We firmly believe in building a strong and evolving base of clinical evidence to inform medical practice and benefit patients worldwide.”

Medtronic’s commitment to clinical evidence includes more than 100 clinical trials scoped to include more than 100,000 patients worldwide. Among these landmark studies:

* SCD-HeFT (Sudden Cardiac Death in Heart Failure) trial, which showed that the use of an ICD in people with heart failure reduces death by 23 percent;
* CARE-HF (Cardiac Resynchronization in Heart Failure) trial, which demonstrated that CRT reduced death by 40 percent in patients with moderate to severe heart failure;
* MIRACLE (Multicenter InSync Randomized Clinical Evaluation) trial, which resulted in the United States Food & Drug Administration (FDA) approval of the first CRT device for the treatment of heart failure;
* IMPROVE HF (Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting), the largest multifaceted heart failure study in the United States outpatient setting. It is designed for clinicians who want to improve patient outcomes by increasing awareness and adoption of published heart failure treatment guidelines, which are shown to reduce the risk of death by 77 percent;
* MOMIJI (Miracle-ICD Outcome Measured In Japanese Indication) trial, the first large-scale, post-market study in Japan sponsored by a medical device company.