MD Conference Express ESC 2012 - (Page 15)
Medical University of Graz, Graz, Austria, showed that spironolactone significantly improves diastolic function and blood pressure (BP) control, but not exercise capacity, in patients with diastolic heart failure (DHF). DHF accounts for more than 50% of all HF cases and clinical outcomes for these patients are poor. While no established therapy exists for DHF, there is strong evidence for a benefit from aldosterone antagonists in patients with reduced left ventricular ejection fraction (LVEF) [Chatterjee S et al. Am J Med 2012], and aldosterone has been implicated in the pathogenesis of DHF via aldosterone receptor mediated myocardial fibrosis, hypertrophy, and vascular stiffening. Aldo-DHF was a multicenter, randomized, placebocontrolled, double-blind, parallel-group study conducted to assess the safety and efficacy of the aldosterone receptor antagonist spironolactone on diastolic function and exercise capacity in patients with DHF after 1 year of therapy. Subjects were required to have documented stable chronic HF (NYHA II/III), echocardiographic evidence of diastolic dysfunction ≥Grade 1 or atrial fibrillation, EF ≥50%, and peak VO2 <25 mL/kg/min. Coprimary endpoints were change in diastolic function (mitral inflow E velocity to tissue Doppler e´ [E/e´ ratio]) and maximal exercise capacity (peak VO2 on bicycle spiroergometry) at 12 months [Edelmann F et al. Eur J Heart Fail 2010]. Subjects (mean age 67 years, 52% women, ≥85% NYHA class II) were randomized to spironolactone (n=213) or placebo (n=209). Baseline E/e´ was 12.7±3.6 and 12.8±4.4 and peak VO2 was 16.3±3.6 and 16.4±3.5 mL/kg/min in the spironolactone and placebo groups, respectively. Median NT-proBNP was 179 ng/L in the spironolactone group (range, 81 to 276) and 148 ng/L (range, 80 to 276) in the placebo group. Approximately 92% of patients had controlled hypertension at study entry. Mean estimated glomerular filtration rate was ~78 mL/min/1.73 m2. Spironolactone (25 mg QD) significantly improved diastolic function (p<0.001) but did not improve exercise capacity. Treatment effects were consistent across all subgroups analyzed. Spironolactone induced significant structural reverse remodeling (LV mass index p=0.009) and significant reductions in NT-proBNP plasma levels (p=0.03), but did not improve NYHA class, left atrial volume index, or quality of life. Spironolactone was also associated with significant reductions in both systolic and diastolic BP beginning at 3 months, yet the effects of spironolactone on cardiac structure and function remained significant after adjusting for BP changes. Adverse events occurred significantly more often with spironolactone, including
mild worsening of renal function (36% of spironolactone subjects vs 21% of placebo subjects; p<0.001); new or worsening anemia (16% vs 9%; p=0.03), gynecomastia (4% vs <1%; p=0.02), and nonsevere (<5.0 mmol/L) increases in serum potassium levels (21% vs 11%; p=0.005). One patient in the spironolactone group died (vs none of the placebo subjects). There was no difference in the rate of hospitalization. Additional data on the long-term efficacy and safety of spironolactone in patients with DHF will come from the Trial of Aldosterone Antagonist Therapy in Adults With Preserved Ejection Fraction Congestive Heart Failure [TOPCAT; NCT00094302] study, which is expected to report during 2013. TOPCAT is a multicenter, international, randomized, double-blind, placebo-controlled trial of spironolactone in 3515 adults with HF and LVEF ≥45%. The trial duration is ~6 years with an expected average subject follow-up of 3.45 years. The primary endpoint is a composite of cardiovascular mortality, aborted cardiac arrest, or hospitalization for the management of HF.
FAME 2 Results
Written by Lori Alexander
Percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) plus the best available medical therapy (MT) improves outcomes in patients with stable coronary artery disease (CAD) compared with optimal MT alone. The benefit is primarily due to a lower rate of rehospitalization for urgent revascularization (UR). These findings, from the Fractional Flow Reserve-Guided Percutaneous Coronary Intervention Plus Optimal Medical Therapy versus Optimal Medical Therapy Alone in Patients with Stable Coronary Artery Disease [FAME 2; NCT01132495] trial, were reported by Bernard De Bruyne, MD, PhD, Onze-Lieve-Vrouw Clinic, Aalst, Belgium. In prior studies, PCI has failed to to improve the prognosis for patients with stable CAD. However, Prof. De Bruyne and the FAME 2 investigators hypothesized that PCI plus MT would improve outcomes for patients with stable CAD if the presence of lesions that produced ischemia were confirmed by measurement of FFR. FFR-guided PCI was superior to angiography-guided PCI in the initial FAME trial [Tonino PA et al. N Engl J Med 2009]. The results of FAME 2 were simultaneously published to coincide with the presentation of the study [De Bruyne B et al. N Engl J Med 2012]. The researchers measured FFR in patients with stable CAD for whom PCI was being considered. Patients who had at least 1 functionally significant stenosis (FFR ≤0.80)
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Official Peer-Reviewed Highlights from the European Society of Cardiology Congress 2012
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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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