Report of the Working Group on
Drug Eluting Stents and Bare Metal Stents:
Summary of a Telephone Meeting

January 30, 2007

The Working Group on Drug Eluting Stents met in a 2 hour conference call on January 30 to discuss the most effective role for the NHLBI in advancing the science related to stents, both Drug Eluting and Bare Metal Stents: where we are, where we should be going and a possible leadership role for the NHLBI. The panel included representatives from academia, industry and FDA. A roster of attendees is attached.

The general sense of the group was that there was no need for a large, NHLBI-sponsored randomized clinical trial at the present time, but that a number of more basic questions should be addressed. A summary of the issues addressed and the conclusions follows.

Question: Is there a role for the NHLBI in better understanding the safety signal associated with DESs?
Yes, the NHLBI does have a role because the Institute:

• Lends credibility to results since the Institute is free of vested interests;
• Can garner cooperation from various industrial and university stakeholders in sharing data;
• Conducts mechanistic studies that would not attract funding from other sponsors.

Question : Are there important problem areas to which the NHLBI might make a unique contribution?
Yes, there are a number of areas to which the NHLBI could make a significant contribution. These include:

• Examples of clinical research issues or goals:
• Determine the rate of adverse events when DES (and BMS) patients are followed for much longer periods than has heretofore been the case
• Develop an approach to standard data collection across studies; describ stent patients clinically, (including demographics, disease state [i.e. extent of coronary disease and its clinical stability, describe associated co-morbidities, procedure history, procedure received, procedural results and follow-up results.
• Use of clinical modeling for risk stratification,
• Determine the optimal duration of dual antiplatelet therapy;
• Potential effects of new anti-platelet drugs on DES outcome,
• Determine how patients who must stop dual antiplatelet therapy, e.g. for non-cardiac surgery, be most effectively bridged to a period when they can resume dual antiplatelet therapy
• Examine the role of stent malaposition in later stent thrombosis
• Determine the role of optical coherence tomography and coronary angioscopy in identifying patients at risk of subacute stent thrombosis

• Examples of mechanistic questions and goals:
• Study the processes involved in healing following BMS placement?
• Examine how does each component of the DES interact with the healing process
• Determine the drug elution kinetics affecting the healing process?
• Use atherosclerotic animal models to study both BMS and DES;
• Genotypes of P 2Y 12 platelet receptors in identifying hyporesponders to clopidogrel and subsequent stent thrombosis
• Determine the optimal type, dose, and duration of antiplatelet therapy?
• Investigate effective management of patients requiring premature termination of antiplatelet therapy for non-elective surgery.

Question : What organizational constructs are likely to be the most cost-effective for the NHLBI to employ?

• Registries: the clinical research issues above (with the exception of the duration of dual antiplatelet therapy) could be addressed with carefully designed registries. A key role for the NHLBI would be to broker data sharing among registries and use of common data collection approaches.
• Mechanistic and some clinical studies could be added to already existing trials at a cost lower than setting up de novo infrastructure.

Recommendations

1. A large trial that would assess DES versus BMS for freedom from death or MI is not recommended. No other RCT was suggested.
2. NHLBI should explore serving as a clearinghouse for sharing of data among registries and as the nidus for developing common data collection formats.
3. An attempt should be made to imbed mechanistic and other ancillary questions inside ongoing trials to reduce cost.
4. Establish collaboration between the NHLBI, FDA, academic centers and industry.