Medical device titan Medtronic (NYSE:MDT) is the only company with the green light from U.S. healthcare regulators to market a drug-eluting stent specifically for patients with diabetes in addition to coronary artery disease, but that victory was hard-won.
The pathway to approval included 5 clinical trials spanning more than 5,000 patients, comparing results in patients without diabetes, those with non-insulin treated diabetes and patients with insulin-treated diabetes, who fared the worst among the trio.
The story of how the device won the unique indication for stenting in patients with diabetes, who traditionally suffer worse outcomes than their peers, was the subject of an in-depth analysis published this month by the American College of Cardiology’s journal JACC: Cardiovascular Interventions.
The report included 2 separate analysis of study data gathered amid Medtronic’s global RESOLUTE program, which enrolled 5,130 patients in total, 1,535 of them diabetics.
Medtronic’s February 2012 FDA approval to market the Resolute Integrity DES for use in diabetics was based on 5 trials under the global program: RESOLUTE U.S., RESOLUTE all-comers, RESOLUTE international, RESOLUTE 1st-in-man and RESOLUTE Japan, the FDA noted at the time.
The medical device company began enrolling patients in the RESOLUTE global program as far back as December 2005, when recruitment started for the RESOLUTE 1st-in-man trial. The U.S. trial was the last to complete enrollment, treating the last of more than 1,400 patients in December 2009, according to the study.
A team of researchers analyzed the data from those studies, concluding, as the FDA did, that the Resolute Integrity DES "is safe and effective in patients with diabetes," according to the report.
Diabetics have long been a difficult-to-treat subset of patients with coronary artery disease, and many have had to result to open-heart surgery because they frequently have narrower arteries, longer lesions and a higher rate of treatment failure.
"A common co-morbidity of coronary artery disease, diabetes affects approximately 1/3 of patients who receive coronary stents and historically has been associated with adverse clinical outcomes," according to a Medtronic press release. "New research presented in the journal article, however, shows that treatment with the Resolute drug-eluting stent led to similarly positive outcomes for diabetes patients who were not taking insulin and for patients without diabetes."
The published report includes 2 separate analyses of RESOLUTE study data. The 1st analysis examined outcomes in the 878 standard-risk diabetics, finding a 7.8% 1-year target vessel failure rate, about half the benchmark level of 14.5% set in accordance with the FDA.
"The results of this analysis led to FDA approval of a unique diabetes indication for the Resolute Integrity drug-eluting stent in February 2012," according to Medtronic.
The 2nd analysis included in the published report evaluated cumulative target lesion failure rates among the 5,000-plus patients, separating them into those without diabetes, those with non-insulin-treated diabetes and those with insulin-treated diabetes.
Patients without diabetes and diabetics not taking insulin experienced "low and comparable" 2-year rates of target lesion failure of about 8.4% and 8.9%, respectively. Diabetic patients taking insulin had a "predictably higher" TLF rate of 16.7%, Medtronic noted.
"These two analyses offer interventional cardiologists worldwide increased confidence when making treatment decisions about the coronary artery disease of patients with diabetes mellitus, who have historically experienced worse clinical outcomes following coronary stent procedures," lead author Dr. Sigmund Silver said in prepared remarks, on behalf of Medtronic.
