Microsoft powerpoint - clever primary results aha 2011_final-nopw.pptx
Claudication Treatment Comparative Effectiveness: Authors:
Timothy P Murphy, Donald E. Cutlip, Judith G. Regensteiner, Emile R. Mohler III, David J. Cohen, Matthew R. Reynolds, Beth A. Lewis, Joselyn Cerezo, Niki C. Oldenburg, Claudia C. Thum, Alan T. Hirsch. Presenter:
Alan T. Hirsch, Chair, on behalf of the CLEVER Study Investigators
Acknowledgements and Disclosures Acknowledgements: The CLEVER Study was sponsored by the National Heart Lung and Blood Institute (grants HL77221 and HL081656), and also received financial support from Cordis/Johnson & Johnson (Warren, NJ), eV3 (Plymouth, MN), and Boston Scientific (Natick, MA). Otsuka America, Inc., (San Francisco, CA) donated cilostazol for all study participants throughout the study. Omron Healthcare Inc., Lake Forest, IL donated pedometers. Krames Staywell, San Bruno, CA, donated print materials for study participants on exercise and diet. Disclosures: Timothy P. Murphy, M.D.: Research grant support - Abbott Vascular, Cordis/Johnson&Johnson, Otsuka Pharmaceuticals; consultant - Microvention/Terumo, Inc.; David Cohen, M.D.: Research grant support - Medtronic. Boston Scientific, Abbott Vascular, Medrad; consultant - Medtronic, Inc.; Matthew R. Reynolds, M.D., M.Sc. : Consultant - Medtronic, Inc.; Alan T. Hirsch, MD.: Research Grant Support - Cytokinetics, Viromed, Abbott Vascular; consultant - Merck, Pozen, Novartis, AstraZeneca. Background
Claudication is the most frequent symptom of peripheral
artery disease (PAD), and is experienced by an estimated 2 million Americans
Current therapeutic options include home exercise;
supervised exercise; claudication pharmacotherapy (cilostazol); or endovascular procedures
Invasive stent procedures have not been shown to offer
better claudication improvement than supervised exercise; stenting is reimbursed, but supervised exercise is not
Patients with proximal (aortoiliac) PAD are often highly
symptomatic, and are generally considered ideal for stent revascularization
Study Objectives
1. To test whether aortoiliac stenting (ST) and supervised
exercise therapy (SE) are superior to optimal medical care (OMC) -- as measured by peak walking time (PWT) at 6 months -- in patients with claudication due to aortoiliac peripheral arterial disease (PAD).
2. If these comparisons are positive, to test whether
stenting is superior to supervised exercise for the same endpoint. Population
Moderate to severe claudication (2-11 min on Gardner treadmill protocol or up to 5.5 METS)
Hemodynamically significant aortoiliac PAD confirmed by
non-invasive vascular lab testing or advanced imaging
No other co-morbid diseases that limited walking
No critical limb ischemia (rest pain, non-healing wound or
SFA disease allowed and endovascular treatment
permitted by protocol, but not required in any patients
Treatment Strategies Optimal Medical Care (OMC): Cilostazol 100 mg bid as tolerated, written and oral advice
about exercise and diet, with monthly coordinator contact
Supervised Exercise (SE): OMC plus 78 sessions of supervised exercise, 3x/wk, for 1 Stenting (ST): OMC plus stent revascularization of aortoiliac PAD Endpoints Primary Endpoint: Peak Walking Time (PWT) on a graded treadmill test Secondary Endpoints: Claudication Onset Time (COT) Community-based walking by pedometer Quality of life (QOL) by WIQ, PAQ, SF-12 Atherosclerosis biomarkers Primary Endpoint Assessed at Six (6) Months Eighteen (18) months long-term follow-up pending Demographic and Medical History Characteristics Age, years 62.4±8.0 64.1±9.5 64.9±10.2 Diabetes (%) Hypertension (%) Current smoking (%) Hypercholesterolemia (%) Prior stroke (%) Prior myocardial infarction (%) Prior use of cilostazol (%) Baseline Physiologic, Biochemical, and Anthropomorphic Characteristics Blood Pressure and ABI SBP (mmHg) DBP (mmHg) Ankle-Brachial Index 0.73±0.2 0.66±0.2 0.66±0.2 Biochemical Profile LDL (mg/dl) HDL (mg/dl) 48±15 0.94 Triglycerides (mg/dl) 147±142 HbA1c (%) 6.3±1.3 6.1±1.1 6.4±1.2 Anthropomorphic Characteristics 28.1±5.9 27.7±5.2 29.3±6.0 Waist Circumference (cm) Baseline Performance Characteristics Treadmill Walking PWT (minutes) 5.5±2.5 5.3±2.3 5.2±2.0 COT (minutes) 1.7±0.7 1.6±0.9 1.7±0.83 Community-based Walking Hourly Free-Living Steps 343±411 264±216 291±196 Treatment Delivery Cilostazol Compliance: >90% in all treatment groups Exercise Compliance: 71% Technical Success of Stenting: All ST patients successfully stented Pre-procedure mean lesion length 3.9±3.4 cm Mean stenosis 83±19%; post-procedure stenosis 5±8% ABI 0.66±0.2 at baseline, improved by 0.29±0.33 Crossover Rates: None at six months Primary Endpoint: Peak Walking Time Change from Baseline to Six (6) Months Pair-Wise Comparisons Difference (minutes) Exercise vs. OMC 4.6 (95% CI, 2.7-6.5) <0.001 Stenting vs. OMC 2.5 (95% CI, 0.6-4.4) Exercise vs. Stenting 2.1 (95% CI, 0.0-4.2) Claudication Onset Time Change from Baseline to Six (6) Months Pair-Wise Comparisons Difference (minutes) Exercise vs. OMC <0.003 Stenting vs. OMC Exercise vs. Stenting Community Walking Change from Baseline to Six (6) Months Pair-Wise Comparisons Difference (steps) Exercise vs. OMC Stenting vs. OMC Exercise vs. Stenting Walking Impairment Questionnaire Change from Baseline to Six (6) Months SE vs. OMC ST vs. OMC <0.001 <0.001 <0.001 Peripheral Artery Questionnaire Change from Baseline to Six (6) Months SE vs. OMC ST vs. OMC <0.001 <0.001 <0.001 Conclusions
In patients with moderate to severe claudication and
hemodynamically significant aortoiliac disease, supervised exercise offers better treadmill walking performance outcomes than stent revascularization
Both supervised exercise and stenting are more effective at
increasing walking distance compared to pharmacotherapy alone
Aortoiliac stent revascularization was associated with better
QOL scores than patients treated with supervised exercise, which is unexplained
Ongoing 18 month follow-up will provide greater insight into
the relative durability of these treatments, as well as the health economic impact
CLEVER Study Sites Rhode Island Hospital in Providence, RI (Tim Murphy) Henry Ford Hospital in Detroit, MI (Jonathan Ehrman) VA Ann Arbor in Ann Arbor, MI (Venkat Krishnamurthy) Aiyan Diabetes Center in Evans, GA (Janaki Nadarajah) University of Minnesota & Abbott Northwestern Hospital in Minneapolis, MN (Alan T. Hirsch) Jobst Vascular Center in Toledo, OH (Anthony Comerota) Torrance Memorial Medical Center in Torrance, CA (Mark Lurie) Vascular and Endovascular Specialist of Ohio in Mansfield, OH (William Miller) Ochsner Clinic in Metairie, LA (Olusegun Osinbowale) Spokane-Providence Medical Center in Spokane, WA (Stuart Cavalieri) St. Joseph Hospital in Orange, CA (Mahmood Razavi) Forsyth - Salem Surgical in Salem, NC (Ray Workman) Capital Health in Halifax, NS (Robert Berry) Johns Hopkins Hospital in Baltimore, MD (Elizabeth Ratchford) Stony Brook Hospital in Stony Brook, NY (Apostolos Tassiopoulos) University of Pennsylvania in Philadelphia, PA (Emile Mohler) Oregon Health Science University in Portland, OR (John Kaufman) Iowa Clinic in Des Moines, IA (John Matsuura) Peripheral Vascular Associates in San Antonio, TX (Jeffrey Martinez) Central Arkansas Veterans Health Care in Little Rock, AR (Mohammed Moursi)
Anal. Chem. 2004, 76, 4756-4764 Trace Determination of Macrolide and Sulfonamide Antimicrobials, a Human Sulfonamide Metabolite, and Trimethoprim in Wastewater Using Liquid Chromatography Coupled to Electrospray Tandem Mass Spectrometry 1 bel,* Christa S. McArdell, Marc J.-F. Suter, and Walter Giger Swiss Federal Institute for Environmental Science and Technology (EAWAG), CH-8600 Du¨bend
Birchwood MEDICAL PRACTICE in this issue… Birchwood www.birchwoodmedicalpractice.co.uk Partners BIRCHWOOD EDUCATION EVENT – Living with Diabetes This extremely successful event was held at the Horley Methodist Church, on the 24th September. This was another event run by the Birchwood Patient Support Group. The Speakers were Philip Malone Tutor EPPCIC, Chris Bur