December 23rd, 2010
Barry Massie: Looking Back at the Year in Heart Failure
To celebrate the holiday season, CardioExchange asked several of our contributors to choose the most important cardiology-related events of the past year. Barry Massie has focused on heart failure, providing us with his choice of the four most important stories of 2010.
1. Aldosterone antagonists continue their winning streak: Following the convincing reductions in mortality and morbidity with spironolactone in severe heart failure (NYHA class III/IV) in the RALES trial and in the EPHESUS trial with eplerenone in patients with acute MI and LV dysfunction, we saw similar striking reductions (37%) in the composite of cardiovascular death or heart-failure hospitalization in the EMPHASIS trial. Each of these studies was conducted on top of excellent medical therapy, suggesting that aldosterone blockade should be considered earlier in the management of patients with LV systolic function.
2. Migrating cardiac resynchronization therapy (CRT) into milder heart failure: A similar “trifecta” was achieved with CRT this year. Two previous trials, REVERSE and the much larger MADIT-CRT trial, convincingly demonstrated that CRT can improve LV function and induce “reverse LV remodeling” in patients with QRS width ≥120 or 130 msec, respectively, and these changes were associated with a reduction in clinical outcomes (heart-failure worsening and all-cause mortality). RAFT (Resynchronization/defibrillation trial for Ambulatory Heart Failure Trial) randomized 1,798 patients with NYHA II or III heart failure, impaired LV function, and wide QRS to implantation of an ICD or ICD/CRT device, with the addition of CRT resulting in a 26% reduction in the primary composite endpoint of all-cause death or heart-failure hospitalization.
3. Remote monitoring to improve heart-failure outcomes: It seems intuitive that close monitoring of heart-failure patients in clinics or by telephone or other remote techniques can prevent heart-failure worsening by facilitating early intervention; however, the substantial literature on this topic is inconsistent and non-convincing, reflecting heterogeneity of results and, likely, publication bias. Two randomized, controlled trials presented at the AHA meeting (Tele-HF and TIM-HF) compared telephone-based monitoring with usual care, and neither had a favorable effect on its primary outcome (all cause readmission and death in the former and mortality in the latter). How can we explain this result? Successful heart-failure management is complex and requires an involved and adherent patient, reliable and timely information transfer, and timely and appropriate intervention by knowledgeable, experienced practitioners. This may be too much to expect!
4. The ASCEND Trial (presented at AHA 2010): Nesiritide, a recombinant form of B-type natriuretic peptide, was approved in 2001 for the treatment of hospitalized patients with acute heart failure (AHF) on the basis of several relatively small trials that demonstrated modest improvement in dyspnea. It was marketed aggressively as the “first new drug for AHF in a decade,” with sales rapidly rising to an annualized rate of $1 billion. However, two meta-analyses suggested a possible increase in mortality and worsening renal function. The ASCEND trial enrolled 7,141 AHF patients, who were randomized to usual care or nesiritide. The active drug produced a marginal improvement in dyspnea at 6 and 24 hours, but though nominally statistically significant, it did not meet the prespecified threshold for positivity. The secondary endpoint of 30-day death or heart-failure readmission was non-significantly lower with nesiritide. Thus, nearly 10 years after its approval, ASCEND demonstrated that nesiritide was safe but had limited benefit in AHF patients.