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