1. CLEVER Trial: 6 Month Outcomes Discussant: Michael S. Conte MD, FAHA University of California, San Francisco AHA Scientific Sessions 2011 Late-Breaking Clinical Trials

2. Need for Evidence-Based PAD Care PAD affects upwards of 8 million Americans Intermittent Claudication (IC) is the most common symptom Recent explosion in number of interventions for IC –Not sustainable in current healthcare environment –Largely market driven, not evidence-based Key Evidence Gaps- need for a CER agenda in PAD –Lack of high quality RCTs –Lack of high quality registries –Lack of consensus on critical outcome measures Evidence-to-Practice Translation Gaps –Generalizability of results from trials –Economic incentives –Turf issues –Reimbursement policies e.g. exercise therapy

3. CLEVER Multi-center RCT Multidisciplinary leadership Compare treatment strategies for IC in pts with Aorto-Iliac Occlusive Disease (AIOD) –Optimal Medical Care vs Supervised Exercise vs Stent NHLBI funded Enrollment initiated: April 2007 Enrollment completed: January 2011 (N=119) Primary 6-month outcomes: November 2011

4. CLEVER: What Have We Learned? “Optimal Medical Care” has little clinical benefit –Cilostazol group had less than expected improvement Both Supervised Exercise and Stenting have significant beneficial effects over OMC at 6 months –SE resulted in better treadmill performance (objective) –ST resulted in better self-reported QoL We lack understanding on the mechanisms of treatment benefit, and the optimal outcome measure for IC trials that correlates with daily life Potentially confounded by unblinded nature and training effects associated with Tx assignments

5. CLEVER: Key Questions How representative is the study cohort? –Appears highly selected with favorable anatomy (lesion length) –Compliance high = highly motivated Is cilostazol ineffective in AIOD? Is treadmill performance the best measure for comparing effectiveness of IC treatment strategies? –Training effect in treadmill-based SE is inherent –Needs correlation with function in daily life Did lack of subject blinding influence the outcomes? Will the observed benefits be durable?

6. CLEVER: Limitations Highly selected cohort; results may not be generalizable Challenges of recruitment reflect lack of equipoise in the field, especially in AIOD –Unclear if results will alter perceptions –SFA disease treatment is more controversial Discordance between treadmill and QoL outcomes further limit the trial’s potential impact on practice Await longer term data for durability of benefits Unlikely to influence practice unless policies change –Reimbursement for SE still not available for Medicare beneficiaries –Reimbursement for ST significant and not linked to outcomes –Providers and industry incentivized to provide invasive treatments

7. CLEVER: Aftermath Need greater investment in CER in PAD –Both multi-center RCTs and registries needed –Public-private partnerships for funding –Optimize trial designs and recruitment via broad stakeholder engagement More trials in IC are specifically needed –Clarify best outcome measures that correlate with patient improvement in everyday life –Stratify by anatomic and clinical factors Should increase pressure on CMS to provide reimbursement for Supervised Exercise programs Need for more effective pharmacotherapies in IC –Lack of new breakthrough drugs for PAD