Vol 122, No 21
November 23, 2010
Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHD risk-equivalents (clinical trials.gov NCT00685776). Eligible patients, who are treated to NCEP-ATP III LDL-C treatment goal with a statin other lipid-modifying medications, are randomized to anacetrapib 100 mg or placebo for 18 months, followed by a 3 month, post-study follow-up. The primary endpoints are percent change in LDL-C and the safety and tolerability of anacetrapib, including the evaluation of adjudicated major adverse CV events. Results: A total of 2757 patients were screened at 153 centers in 20 countries and 1623 patients were randomized into the trial. Lipid results, clinical CV events and other safety assessments for the 18-month treatment phase will be completed in September 2010 and will be available for presentation at the AHA meeting in November 2010.
Author Disclosures: C.P. Cannon: Research Grant; Modest; Accumetrics, Takeda, Intekrin. Research Grant; Significant; Merck, GSK, AstraZeneca. Ownership Interest; Modest; Automed- ics. Consultant/Advisory Board; Modest; BMS/Sanofi (funds to charity), Novartis (funds to charity), Alnylam (funds to charity). S. Shah: Employment; Significant; Merck. Ownership Interest; Modest; Merck. H.M. Dansky: Employment; Significant; Merck. Ownership Interest; Significant; Merck. M. Davidson: Employment; Significant; Radiant Research. Research Grant; Significant; Merck, Abbott, AstraZeneca, Daichi-Sankyo, DiaDexus, GSK, Kinemed, Roche, Sanofi Aventis, Takeda, Vindico. Consultant/Advisory Board; Significant; Abbott, AstraZeneca, Daichi Sankyo, Merck, Roche, Takeda. Other; Significant; Omthera, Sonogene. E.A. Brinton: Research Grant; Significant; Abbott, GSK, Merck. Speakers Bureau; Significant; Abbott, GSK, Merck, Wagstaff and Cartmell. Consultant/Advisory Board; Modest; Abbott, AstraZeneca, Atherotech, GSK, Merck, Kronos Longevity Research Institute. A.M. Gotto, Jr.: AstraZeneca, Dupont. Consultant/Advisory Board; Significant; Kowa, Merck, Vatera Capital. Other; Significant; Aegerion Pharmaceuticals, Arisaph Pharmceuticals. M. Stepanavage: Employment; Signifi- cant; Merck. Ownership Interest; Modest; Merck. S. Xueyu Liu: Employment; Significant; Merck. Ownership Interest; Modest; Merck. P. Gibbons: Employment; Significant; Merck. Ownership Interest; Modest; Merck. T.B. Ashraf: Employment; Significant; Merck. Ownership Interest; Modest; Merck. J. Zafarino: Employment; Significant; Merck. Ownership Interest; Modest; Merck. Y.B. Mitchel: Employment; Significant; Merck. Ownership Interest; Significant; Merck. P. Barter: Research Grant; Significant; Merck, Pfizer, Roche. Other Research Support; Significant; AstraZeneca. Honoraria; Modest; Abbott, Pfizer. Honoraria; Significant; Merck, AstraZeneca, Roche. Consultant/Advisory Board; Modest; AstraZeneca, CSL, Merck, Pfizer, Roche, Sanofi-Aventis.
21826 Symplicity HTN-2: International, Multicenter, Prospective, Randomized, Controlled Trial of Endovascular Selective Renal Sympathetic Denervation for the Treatment of Hypertension
Murray Esler; Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
Background: Renal sympathetic afferent and efferent nerves play a seminal role in mediating hypertension. The objective of this international, multicenter, prospective, randomized, controlled trial was to demonstrate that endovascular ablation of the renal nerves is a safe and effective treatment for uncontrolled hypertension. Methods: Adults age 18–85, with systolic blood pressure 160 mmHg (150 mmHg systolic in type II diabetes) despite demonstrated compliance with at least three antihypertensive medications from different drug classes were recruited at 24 centers with ethics committee approval in Europe and Australia. Patients were excluded if estimated GFR was 45ml/min and if renal artery anatomy revealed either significant renal artery stenosis or precluded safe denervation. Subjects were required to demonstrate compliance to medical therapy, before randomization to either therapeutic renal denervation (RDN) with continuing medical therapy or continuing medical therapy (CON); twenty-seven patients were excluded after screening and before randomization when office blood pressure was found to be 160 mmHg after the compliance screening period. The primary endpoint was change in office systolic BP between baseline and 6-months. Secondary endpoints include both acute and chronic procedural safety. Initial Demographics: Between June 2009 and March 2010, 106 patients were randomized: CON 54 and RDN 52. Patients were taking an average 5.3 anti-HTN medications with an average baseline BP of 178/97 / 17/16 mmHg. Patients generally had similar baseline characteristics, with RDN having lower baseline eGFR (77 vs. 87 ml/min) (Table 1). Conclusions: Bilateral renal denervation was successfully performed in 52/52 (100%). There were no serious device or procedure-related complications. Complete effectiveness and safety data will be presented.
21774 Results of the First Major Clinical Trial of an Oral Agent Inducing Apo A1 Synthesis: A New Approach to HDL Raising and CV Risk Modification
Stephen J Nicholls, Cleveland Clinic, Cleveland, OH; Christie M Ballantyne, Baylor, Houston, TX; John J Kastelein, Academic Med Cntr / Univ of Amsterdam, Amsterdam, Netherlands; Allen J Taylor, Washington Hosp Cntr, Washington, DC; Allan Gordon, Jan Johansson, Resverlogix Pharmaceuticals, San Francisco, CA; Steven E Nissen; Cleveland Clinic, Cleveland, OH
Purpose: High-density lipoproteins (HDL) and reverse cholesterol transport remains a major focus in the development of new anti-atherosclerotic therapies. While the optimal therapeutic approach to promote HDL functionality remains uncertain, there is considerable consensus that the ability to increase synthesis of its major protein, apolipoprotein A1 (apoA1) represents a highly promising approach. The aim of this study was to evaluate the efficacy and safety of the first oral agent that induces synthesis of apoA1 (RVX-208) in patients with stable coronary artery disease. Study Design: A double-blind, randomized controlled trial of patients with stable coronary artery disease, on a stable dose of statin therapy for at least 30 days, treated for 12 weeks with RVX-208 (i) 100 mg/daily, (ii) 200 mg/daily, (iii) 300 mg/daily or (iv) placebo. Sample Size: Of 360 patients screened, 299 patients were randomized in 35 centers in the United States between January and February 2010. Endpoints: The primary endpoint is the percentage change in apoA1 levels in patients treated with RVX-208 compared to placebo. Additional objectives include characterizing the dose and time response relationships for apoA1, major lipid parameters and HDL subclasses and safety and tolerability of RVX-208 over the 12-week treatment period. Power Calculations: It was estimated that 70 patients would be required in each treatment group to provide 80% power to detect an 8% increase in apoA1 compared to placebo assuming a standard deviation of 15%. Conclusion: The last patient received their final dose of treatment in May 2010. The initial efficacy and safety data will be available during the summer and be ready for full presentation soon thereafter. This study provides the first opportunity to characterize the early experience of apoA1 induction therapy in statin-treated patients with coronary artery disease.
Author Disclosures: S.J. Nicholls: Research Grant; Significant; Resverlogix, AstraZeneca, Novartis, Eli Lilly, Anthera. Honoraria; Modest; Merck, Takeda, Roche. C.M. Ballantyne: Research Grant; Significant; NIH, ADA, AHA. Other Research Support; Significant; Abbott, AstraZeneca, GlaxoSmithKline, Merck, Sanofi-Synthelabo, Schering-Plough. Speakers Bureau; Modest; AstraZeneca, GlaxoSmithKline, Merck, Pfizer, Schering-Plough. Honoraria; Modest; Abbott, AstraZeneca, GlaxoSmithKline, LipoScience, Merck, Novartis, Pfizer, Sanofi-Synthelabo, Takeda. Consultant/Advisory Board; Modest; Abbott, Amylin, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Kowa, LipoScience, Merck, Metabasis, NicOx, Novartis, Pfizer, Resverlogix, Roche, Sanofi-Synthelabo, Takeda. J.J. Kastelein: Research Grant; Significant; Schering-Plough, Merck, Pfizer, Sanofi-Aventis, AstraZeneca, Roche, Isis Pharmaceuticals, Aspreva Pharma. Honoraria; Modest; Schering-Plough, Merck, Pfizer, Sanof-Aventis, AstraZen- eca, Roche, Isis Pharmaceuticals, Lipid Sciences, Lexicon Pharmaceuticals, Kinemed, Novartis. A.J. Taylor: Abbott. A. Gordon: Employment; Significant; Resverlogix Pharmaceuticals. Ownership Interest; Significant; Resverlogix Pharmaceuticals. J. Johansson: Employment; Significant; Resverlogix Pharmaceuticals. Ownership Interest; Significant; Resverlogix Pharma- ceuticals. S.E. Nissen: Research Grant; Significant; Pfizer, AstraZeneca, Novartis, Novo Nordisk, Roche, Daiichi-Sankyo, Takeda, Sanofi-Aventis, Resverlogix, Eli Lilly. Other; Modest; Dr. Nissen consults for many pharmaceutical companies, but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction.
Author Disclosures: M. Esler: Consultant/Advisory Board; Modest; Ardian, Inc.
Clinical Science: Special Reports I
Room S100c Abstracts 21838-21821
21838 The Relationship Between Atrial High-Rate Episodes and Stroke: The Asymptomatic Stroke and Atrial Fibrillation Evaluation in Pacemaker Patients (ASSERT) Trial
Jeff S Healey, Stuart J Connolly, McMaster Univ, Hamilton, Canada; Michael R Gold, Med Univ of South Carolina, Charleston, SC; Alessandro Capucci, McMaster UnivUniversit`a Politecnica delle Marche, Ancona, Italy; Carsten Israel, Klinik f ¨ur Innere Medizin - Kardiologie & Angiologie, Bielefeld, Germany; Isabelle C van Gelder, Univ of Groningen, Groningen, Netherlands; Chu-Pak Lau, Queen Mary Hosp, Hong Kong, Hong Kong; Carlos A Morillo, McMaster Univ, Hamilton, Canada; Eric Fain, St. Jude Med, Sylmar, CA; Mark Carlson, St Jude Med, Sylmar, CA; Stefan H Hohnloser; J. W. Goethe Univ, Frankfurt, Germany
Atrial fibrillation (AF) is one of the most important causes of stroke; however, the majority of AF is clinically silent. Modern pacemakers have the ability to document even transient AF. These brief, “atrial high-rate episodes (AHRE)” are quite frequent in clinical practice. The clarification of their temporal association with stroke will not only determine the need for oral anticoagulation, but will help clarify the precise relationship between AF and stroke. Methods: The ASSERT trial enrolled patients over the age of 65, with a history of hypertension who were receiving a dual-chamber pacemaker for standard indications. The trial excluded patients with a history of AF and those receiving oral anticoagulation. Following a 4 week lead maturation period, AHRE episodes were collected and were adjudicated by a blinded, central committee. For the primary analysis; episodes lasting more than 6 minutes, with a rate 190/minute were considered significant and patients were categorized as to the presence or absence of such episodes during the first 3 months. The primary outcome was ischemic stroke or non-central nervous system (CNS) systemic embolism. Further time-dependent analyses were conducted