No Increased Thrombosis Risk Seen in Early DAPT Interruption With Medtronic's ZES

October 31, 2013—At the TCT 2013: Transcatheter Cardiovascular Therapeutics conference in San Francisco, California, Medtronic, Inc. (Minneapolis, MN) announced the presentation of studies demonstrating that patients with coronary artery disease who received Medtronic's Endeavor or Resolute zotarolimus-eluting stents (ZES) and subsequently interrupted their dual-antiplatelet therapy (DAPT) earlier than current guidelines recommend experienced no increased risk of stent thrombosis at 1 year or more of follow-up.

The OPTIMIZE study was presented during a late-breaking clinical trials session at TCT 2013 and published concurrently by Fausto Feres, MD, et al in the Journal of the American Medical Association (JAMA). Dr. Feres, who serves as principal investigator of the OPTIMIZE study, is an interventional cardiologist at the Instituto Dante Pazzanese de Cardiologia in São Paulo, Brazil.

The OPTIMIZE study is a prospective, multicenter randomized controlled trial designed to evaluate the clinical implications of DAPT discontinuation after 3 months as compared with the standard 12 months of DAPT following implantation of any single drug-eluting stent. The trial compared 1-year outcomes in patients who received the Endeavor ZES and stayed on DAPT for either 3 or 12 months.

The company stated that OPTIMIZE was rigorously conducted at 33 medical centers in Brazil to evaluate the optimal duration of DAPT with clopidogrel after treatment with the Endeavor ZES in real-world clinical practice. The study enrolled 3,119 patients requiring percutaneous coronary intervention (PCI) who received an Endeavor ZES and were then equally randomized to either 3 months (n = 1,563) or 12 months (n = 1,556) of DAPT. The primary endpoint was net adverse clinical and cerebral events (NACCE, a composite of all-cause death, myocardial infarction, stroke, or major bleeding) at 1 year. The main exclusion criteria were primary or rescue PCI for ST-segment elevation myocardial infarction, lesion located in a saphenous vein graft, and previous PCI with DES (drug-eluting stent).

Medtronic reported that the OPTIMIZE study met its primary endpoint by showing noninferiority in NACCE rates at 1 year between patients treated with 3 months versus 12 months of DAPT (6% vs 5.8%; P for noninferiority = .002) after implantation of an Endeavor DES. In addition, there was no statistically significant increase in the occurrence of Academic Research Consortium definite or probable stent thrombosis at 1 year (0.8% with 3 months of DAPT vs 0.8% with 12 months of DAPT; P = not significant).

Medtronic also announced that data from two analyses of the Resolute ZES presented at TCT demonstrated favorable clinical outcomes in patients who interrupted their DAPT early and further reinforced the safety profile of ZES.

Ajay Kirtane, MD, presented an analysis of approximately 5,000 patients who received a Resolute ZES that showed that DAPT interruption after 1 month of device implantation posed no increased risk of stent thrombosis at 3 years of follow-up. Of the 684 patients who interrupted their DAPT after 1 month and before 1 year, none (0%) experienced stent thrombosis out to 3 years. Dr. Kirtane is Chief Academic Officer and Director of the interventional cardiology fellowship program at New York-Presbyterian Hospital/Columbia University Medical Center in New York, New York.

Additionally, Deepak Bhatt, MD, presented a related analysis on an expanded patient pool of approximately 7,000 patients who received a Resolute ZES. Consistent with Dr. Kirtane's findings, the risk of stent thrombosis at 1 year did not increase for those patients who interrupted their DAPT after 1 month compared to those who did not. Dr. Bhatt is Chief of Cardiology at the VA Boston Healthcare System, Director of the Integrated Interventional Cardiovascular Program at Brigham and Women's Hospital and the VA Boston Healthcare System, and Professor of Medicine at Harvard Medical School.

In Medtronic's press release, Dr. Feres commented, “Our findings show that stopping DAPT after 3 or 12 months following implantation of the Endeavor DES made no difference in relation to NAACE and stent thrombosis at 1 year of follow-up. More generally, they also support the notion that stent selection has a bearing on safety outcomes. From the results of the OPTIMIZE study and other new data from the RESOLUTE clinical program that were presented earlier this week, a reevaluation of DAPT duration following implantation of Medtronic's ZES is probably warranted.”

Medtronic stated that it continues to support adherence to all guidelines related to stenting. DAPT guidelines for patients who receive a DES differ by geographic region, but generally recommend daily compliance for 6 to 12 months. The applicable guidelines are referenced in the country-specific labeling for each device, noted the company.

Medtronic advised that earlier this year, the company received approval to update the Resolute Integrity stent's European CE Mark labeling to reflect the fact that DAPT interruption or discontinuation after 1 month posed “low and no increased risk” of stent thrombosis at 1 year. The United States labeling for the Resolute Integrity ZES recommends 12 months of DAPT, which is consistent with the guidelines of the American College of Cardiology/American Heart Association/Society of Cardiovascular Angiography and Interventions.