Groningen, the Netherlands - Beta blockers might be of benefit in patients with advanced heart failure and preserved left ventricular ejection fraction (LVEF), say researchers in the Netherlands [1].

"This prospective observational study is the first to indicate that treatment with beta blockers reduces mortality in patients with advanced HF and preserved LVEF," say Dr Daniela Dobre (Northern Centre for Healthcare Research, University Medical Centre Groningen, the Netherlands) and colleagues in their paper published online October 4, 2006 in the European Journal of Heart Failure.

However, they warn that the favorable effects of beta blockers in this population of HF patients needs to be confirmed in prospective, randomized clinical trials. Dobre told heartwire that a number of studies of this nature are underway, including the Japanese Diastolic Heart Failure Study [2].

Dobre explained to heartwire that most patients who have HF with preserved LVEF also have diastolic dysfunction, but that this is not always the case and therefore the term "diastolic heart failure" is in dispute. In general, patients who have heart failure with preserved LVEF are older, more likely to be female, and more likely to have hypertension than patients with HF and reduced ejection fraction.

There is clear evidence that beta blockers increase survival in HF patients with reduced EF, she notes, but only two studies have looked at beta blockers in HF with preserved EF, one of which was the EuroHeart Failure Survey, an observational study with only short-term (three-month) results, and a small randomized controlled trial of propranolol, published in 1997.

"No large randomized trial or cohort study addressing the role of beta-blocker therapy in HF with preserved LVEF has yet been completed. Such information is particularly important given the high percentage of patients with [this type of] HF. . . and the lack of evidence-based recommendations for its management," she and her colleagues observe.

Despite the paucity of guidance on the treatment of patients with HF and preserved EF, Dobre said that in practice many of these patients are on a beta blocker anyway because of hypertension.

They prospectively studied a cohort of 443 patients with advanced HF and preserved LVEF (mean age 78 years, 56% female) who were admitted to Rijnland General Hospital, in Leiderdrop, the Netherlands, between January 2000 and June 2005. Overall, 227 patients had a beta blocker prescribed at discharge—including carvedilol (up to a dose of 50 mg/day), metoprolol (up to 200 mg), bisoprolol (up to 10 mg), and nebivolol (up to 10 mg). Follow-up was calculated from the day of discharge until July 2005. Deaths were obtained from hospital records, next-of-kin review, or by telephone.

They note that their study population was "real life"—for example, it included patients with renal failure—and so the results "may be extrapolated to daily practice in patients with advanced HF and preserved LVEF."

Death (all-cause) occurred in 40 patients (17.6%) who were taking a beta blocker at discharge and in 73 patients (33.8%) who were not. After multivariate adjustment, prescription of a beta blocker was associated with a 43% relative mortality risk reduction (HR 0.57; p=0.01).

Interestingly, higher doses of beta blockers were associated with a significant 49% relative reduction (HR 0.51; p=0.01) in mortality, whereas low-dose therapy was associated only with a nonsignificant 26% risk reduction.

"Our data suggest that beta-blocker benefit [is] dose-related, with high-dose therapy being associated with a lower risk of death than low-dose therapy," they observe.

Dobre told heartwire that many patients were not on the very highest dose of beta blocker because of tolerability problems, "but the message seems to be that a medium/high dose, but not necessarily the target dose, is better than a low/medium dose."

The researchers conclude that the mechanism by which beta blockers provide benefit in HF with preserved LVEF "has not clearly been established," but it is thought that they act through a different primary mechanism than in HF patients with depressed LVEF.