American Heart Association (AHA) Scientific Sessions 2013

Heart Failure Drug Misses Study’s Composite Primary End Point but Reduces Heart Failure Hospitalizations

Currently, no treatments are known to improve prognosis for patients with heart failure (HF) and preserved left ventricular ejection fraction (pLVEF), but mineralocorticoid receptor antagonists have been shown to reduce the risk of death and other major cardiovascular events in patients with reduced ejection fraction HF following myocardial infarction. To see if such agents could have a similar effect in patients with HF and pLVEF, the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial was conducted, which included patients from the United States, Russia, Republic of Georgia, Canada, Brazil, and Argentina. The results of the trial were presented by Marc A. Pfeffer, MD, PhD, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, during a late-breaking abstract session at the AHA 2013 Scientific Sessions.

TOPCAT compared the safety and efficacy of the mineralocorticoid receptor antagonist spironolactone with placebo in 3445 study participants patients aged 50 years and older who had symptomatic HF and an LVEF of 45% or greater. Of these patients, 1722 were randomly assigned to receive spironolactone 15 mg daily, titrated to 45 mg, and 1723 to placebo. Study participants were followed for approximately 3.4 years. Primary end points included cardiovascular death, HF hospitalization, and resuscitation for cardiac arrest. Secondary end points included safety assessments, nonfatal cardiovascular events, development of atrial fibrillation, development of diabetes, and quality of life.

Spironolactone did not show benefit with regard to the study’s composite primary end point, but reduction in hospitalizations for HF, which was a component of the primary end point, was observed. There were 206 (12%) hospitalizations for HF in the spironolactone group versus 245 hospitalizations (14.2%) for HF in the placebo group (hazard ratio, 8.3; 95% confidence interval, 0.69-0.99). All-cause hospitalization and all-cause mortality, however, did not appear to be affected by spironolactone.

No differences in serious adverse events were found in either cohort—spironolactone (48.5%; n=835) and placebo (49.6%; n=855). However, the researchers noted that the use of spironolactone requires careful monitoring of potassium and creatinine at each dose change and follow-up visit to prevent hyperkalemia (≥5.5 mmol/L) and hypokalemia (<3.5 mmol/L). Because the same level of monitoring that occurred during the trial may not be undertaken in clinical practice, the researchers cautioned that worsening renal function and hyperkalemia would likely be more commonly observed in clinical practice.—Kerri Fitzgerald

Study Compares Replacing Versus Repairing Mitral Valves for Severe Ischemic Mitral Regurgitation

The American Heart Association/American College of Cardiology and the European Society of Cardiology guidelines recommend repairing or replacing the mitral valve after a severe ischemic mitral regurgitation, but there has been a paucity of data comparing these interventions. To address this lack of information, a recent randomized trial was undertaken to determine which of these interventions yielded better outcomes. The results of the trial were presented by Michael Acker, MD, Hospital of the University of Pennsylvania, Philadelphia, PA, at the AHA 2013 Scientific Sessions.

The trial included a total of 251 patients, of which 126 were randomly assigned to undergo mitral valve repair and 125 to undergo chordal-sparing replacement. Primary study end points included the degree of left ventricular (LV) reverse remodeling, which was assessed by LV end-systolic volume index (LVESVI) using transthoracic echocardiography at 12 months and group differences based on the Wilcoxon Rank-Sum test, with deaths categorized as lowest LVESVI rank. End points were measured at 30 days and at 6, 12, and 24 months; 24-month follow-up is still ongoing.

The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio, 0.79; 95% confidence interval, 0.42-1.47; P=.45). The results showed no difference in the degree of reverse remodeling and mortality between the two treatment groups. The 30-day mortality rate was 1.6% for the repair group and 4% for the replacement group, and the 1-year mortality rate was 14.3% and 17.6%, respectively.

There was significantly more recurrent mitral regurgitation at 1 year in the repair group compared with the replacement group (32.6% vs 2.3%; P<.001). The mean LVESVI at 12 months among surviving patients was 54.6±25 mL/m² of body-surface area in the repair group and 60.7±31.5 mL/m² in the replacement group.

The researchers noted that the treatment of severe ischemic mitral regurgitation remains controversial, but they are hopeful that these results will help delineate the appropriate therapeutic approach for this condition.—Kerri Fitzgerald

STREAM Trial Compares Treatment Strategies for Cardiac Mortality

Patients who have experienced an acute myocardial infarction (MI) may not always be assessed at a facility that can perform percutaneous coronary interventions (PCIs), placing these patients at increased risk of adverse outcomes. To address this issue, Belgian investigators conducted the STREAM (Strategic Reperfusion Early After Myocardial Infarction) trial, which sought to assess the safety and efficacy of administering tenecteplase, an additional antiplatelet, and an antithrombin before transporting these patients to a PCI-capable hospital for coronary intervention. The results were presented by Peter Sinnaeve, University of Leuven, Leuven, Belgium, at the AHA 2013 Scientific Sessions.

The study randomly assigned 1891 patients to a pharmacoinvasive strategy that included tenecteplase, clopidogrel, and enoxaparin prior to catheterization within 6 to 24 hours with coronary intervention or rescue coronary intervention, or to standard primary PCI within 1 hour of presenting to the hospital. Dose adjustments were made for older patients receiving the pharmacoinvasive strategy.

The primary end points were assessed at 30 days after randomization and included all-cause mortality, cardiogenic shock, congestive heart failure, recurrent MI, hospitalization for cardiac reasons, hospitalization for noncardiac reasons, ischemic stroke, intracranial hemorrhage, and nonintracranial bleeding. The researchers found a nominally lower incidence of mortality, cardiogenic shock, congestive heart failure, and recurrent MI in the pharmacoinvasive group than in the primary PCI group (12.4% vs 14.3%; P=.21). The pharmacoinvasive patients were more likely to undergo coronary artery bypass graft surgery (4.7% vs 2.1%; P=.002), which the researchers speculated may be attributable to the avoidance of urgent PCI in approximately one-third of the pharmacoinvasive patients. In addition, more aborted infarctions were observed in the pharmacoinvasive cohort (11.1% vs 6.9%; P<.01). These results suggest more salvage of ischemic myocardium due to earlier reperfusion. The median time between symptom onset and pharmacoinvasive treatment was 100 minutes, whereas the median time between symptom onset and primary PCI was 178 minutes (P<.001).

One-year data were collected from all patients who survived the first 30 days post-treatment, which revealed similar all-cause and cardiac mortality rates between the two treatment cohorts. Fewer than .08% of patients were lost to follow-up.

Based on STREAM’s results, the researchers concluded that the pharmacoinvasive strategy was similarly effective to the primary PCI intervention. Although the pharmacoinvasive strategy was associated with a small increased risk of intracerebral hemorrhage, there was also a nonsignificant 1.5% absolute lower incidence of cardiogenic shock and congestive heart failure.—Kerri Fitzgerald