MD Conference Express ESC 2012 - (Page 22)

n C L I N I C A L T R I A L H I G H L I G H T S increase in peak concentration per minor allele, while the CES1 polymorphism was associated with a 12% decrease in peak concentration per minor allele (p=8.2x10-8 and p=3.2x10-8, respectively). Two variants were associated with trough concentration: rs4580160 at the CES1P2 locus and rs2244613 at the CES1 locus. The CES1 polymorphism had a significant effect, with a 15% decrease in trough concentration per minor allele (p=1.2x10-8). None of these genetic determinants had a significant association with efficacy, but the CES1 rs2244613 variant did have a significant association with bleeding (Table 1). A significant interaction by treatment arm was also noted: the odds of bleeding with dabigatran decreased 33% for carriers of the CES1 rs2244613 polymorphism, while there was no impact of this genetic variant on bleeding for those receiving warfarin (Figure 1). Approximately one third of Europeans are carriers of this polymorphism, said Prof. Pare. Table 1. Association of Significant Genetic Determinants with Efficacy and Safety. Peak Concentration ABCB1 rs4148738 Event Ischemic stroke or SE Any bleeding Major bleeding Minor bleeding Odds Ratio (95% CI) 0.88 (0.53-1.46) 0.94 (0.82-1.09) 1.14 (0.85-1.52) 0.94 (0.81-1.09) p value 0.62 CES1 rs8192935 Odds Ratio (95% CI) 0.76 (0.43-1.34) 0.89 (0.76-1.03) 0.88 (0.64-1.21) 0.89 (0.76-1.05) p value 0.34 Trough Concentration CES1 rs2244613 Odds Ratio (95% CI) 0.70 (0.33-1.47) 0.67 (0.55-0.82) 0.66 (0.43-1.01) 0.70 (0.57-0.85) p value 0.34 This analysis provides evidence supporting the idea of dose modification of dabigatran based on genotype but requires additional study. The RE-LY AF Registry Written by Lori Alexander Around the world, the average 1-year mortality rate is 10% for patients with a diagnosis of atrial fibrillation (AF) who present to an emergency department (ED) for any reason. The rate is highly variable among different countries, noted Jeffrey S. Healey, MD, McMaster University, Hamilton, Ontario, Canada, who reported on the study. Prof. Healey said that, although AF is a major global disease, most of what is known about the disorder is based on studies conducted in Europe and North America. The baseline results from the Randomized Evaluation of LongTerm Anticoagulation Therapy [RE-LY AF] registry, which were presented at the European Society of Cardiology Congress 2012, demonstrated important regional variations in risk factors and treatment of AF across 47 countries. Dr. Healey and colleagues followed patients for 1 year to document cause-specific mortality and clinical outcomes—most notably, stroke. Of the 18,113 patients enrolled in the RE-LY AF trial, 15,408 (85%) were entered in the registry. The vast majority (98%) had AF (while 2% had atrial flutter), and most (79%) had a prior history of AF. For patients presenting to an ED, AF was the primary diagnosis for 44% of patients and the secondary diagnosis for 56%; for those with a secondary diagnosis of AF, the primary diagnosis varied widely between regions, but heart failure (HF) was the most common. The global average crude mortality rate was 10%, with the highest rates in Africa, South America, and China. When adjustments were made for several variables, the differences were somewhat attenuated, and the rates were highest in Southeast Asia, China, and Eastern Europe (Figure 1). The rates were substantially higher (2-3 fold overall) in all regions when AF was a secondary diagnosis (Figure 2). HF was the primary cause of death overall (34%), followed by infection (12%), and stroke (9.5%). Other causes of death were respiratory failure, cancer, sudden death, and myocardial infarction (all less than 9%). The rate of stroke within 1 year varied among regions, from approximately 8% in Africa to less than 1% in India; the global average was 4%. When adjusted for confounders (age, stroke/transient ischemic attack, HF, hypertension, diabetes, and use of vitamin K antagonists [VKAs]), there 0.44 0.40 0.38 0.13 0.44 0.17 7x10-5 0.06 4x10-4 SE=sytemic embolism. Figure 1. Freedom from Bleeding According to CES1 rs2244613 Carrier Status in the RE-LY Study. 1.0 0.9 Freedom from Bleeding Carriers/Dabigatran (n events=154) Noncarriers/Dabigatran (n events=432) Carriers/Warfarin (n events=110) Noncarriers/Warfarin (n events=215) 0.8 0.7 0.6 0.5 0.4 Dabigatran only: HR=0.70 (95% CI, 0.58 to 0.84); p=0.00016 Warfarin only: HR=1.13 (95% CI, 0.90 to 1.42); p=0.29 Carrier Status X Treatment Interaction p=0.0015 0 200 400 600 Days After Randomization 800 1000 Reproduced with permission from G. Pare, MD. 22 October 2012 www.mdconferencexpress.com http://www.mdconferencexpress.com http://www.mdconferencexpress.com

Table of Contents for the Digital Edition of MD Conference Express ESC 2012

MD Conference Express ESC 2012
Contents
ESC 2012 Clinical Practice Guidelines
TAVI: 10 Years After the First Case
PARAMOUNT Trial Results
TRILOGY ACS Outcomes
Results from the ALTITUDE Trial
Results of the WOEST Trial
Results from the Aldo-DHF Trial
FAME 2 Results
Results from the IABP-SHOCK II Trial
STEMI Mortality Decreases in France While Some Key Risk Factors Increase
Results from the PURE Study
PURE: Treatment and Control of Hypertension
Genetic Determinants of Variability in Dabigatran Exposure
The RE-LY AF Registry
TRA 2°P-TIMI 50 Results
Rivaroxaban of Benefit in STEMI: ATLAS ACS 2-TIMI 51
Ivabradine Effect on Recurrent Hospitalization for HF
CLARIFY: Similar 1-Year Outcomes for Men and Women with Stable CAD
HPS2-THRIVE Study Results
PRoFESS Study Results
Outcomes from the CARDia Trial
Hypertension
Atrial Fibrillation
Heart Failure

MD Conference Express ESC 2012

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