ESTES PARK, COLO. – Introducing five evidence-based interventions in patients with heart failure with reduced ejection fraction would dramatically cut admissions for heart failure, according to Dr. JoAnn Lindenfeld, vice president of the Heart Failure Society of America.
Here are the five interventions: recognizing when to switch from furosemide to another oral loop diuretic with far better bioavailability; up-titrating beta-blocker therapy to the maximum recommended dose as quickly as possible; adding a low-dose aldosterone antagonist to the treatment regimen; prescribing digoxin in symptomatic patients with a low ejection fraction; and identifying and treating iron deficiency, Dr. Lindenfeld said at a conference on internal medicine sponsored by the University of Colorado.
• Loop diuretics: Furosemide, everybody’s favorite low-cost loop diuretic, turns out to have an enormously variable oral bioavailability, ranging from 10% to 90% from patient to patient. It also varies substantially from day to day within the same individual. In contrast, torsemide (Demadex) and bumetanide (Bumex) have a consistently high oral bioavailability of roughly 90%. They are useful alternatives in poorly compensated heart failure patients.
Dr. JoAnn Lindenfeld
"When your patient says they’re not diuresing and you’re pretty sure they’re taking their drugs, or if they’ve had more than one recent admission for heart failure and they’re having trouble with congestion and fluid retention, think about switching to bumetanide or torsemide," said Dr. Lindenfeld, professor of medicine and medical director of the heart transplant program at the university.
"In my own practice, when I have a patient admitted for acute decompensated heart failure with congestion and I don’t find another reversible cause, I will usually switch them," noted Dr. Lindenfeld, who also is codirector of the university’s Center for Women’s Health Research.
In a classic study, 234 patients hospitalized for acute decompensated heart failure were randomized at discharge to torsemide or furosemide in equivalent doses. The torsemide group subsequently had a 52% lower rate of heart failure hospitalization (Am. J. Med. 2001;111:513-21).
Bumetanide is now a pretty inexpensive drug, Dr. Lindenfeld noted. In making the switch, remember that 40 mg of furosemide is equivalent to 1 mg of bumetanide or 20 mg of torsemide.
• Beta-blocker up-titration: Beta-blocker and angiotensin-converting enzyme* (ACE) inhibitor therapy both have a class IA recommendation in heart failure. But what’s the best way to juggle the timing of dual dose increases?
"None of the guidelines says how to manage up-titration, but I strongly believe that once you have somebody on a reasonable dose of an ACE inhibitor – say, 5 mg of lisinopril or the equivalent – then you should go to the beta-blocker and up-titrate it to its maximum," she said. "Then later, come back to the ACE inhibitor and get the patient on the maximum dose of that."
The rationale for this approach is based on a comparison of the outcomes of the landmark beta-blocker trials versus ATLAS, a 3,104-patient trial conducted in the pre-beta-blocker era in which patients were randomized to low-dose lisinopril at 2.5-5 mg/day or high-dose therapy at 32.5-35 mg/day to determine which was better. After 4 years of follow-up, the high-dose group showed a 24% reduction in the risk of heart failure hospitalizations, but no significant advantage in terms of all-cause mortality (Circulation 1999;100:2312-8).
Contrast those results with the outcomes of the major clinical trials for carvedilol, metoprolol, and bisoprolol, each of which featured up-titration to the target dose within 8 weeks whenever possible. All three studies were halted within less than a year because of a roughly 35% reduction in mortality, compared with placebo. And that mortality benefit became apparent at 3 months.
"These are huge reductions in mortality," Dr. Lindenfeld noted. "You don’t want to have a patient come back every 4 weeks to up-titrate their ACE inhibitor for 5 months and miss the opportunity to get the patient on an effective dose of a beta-blocker, when the lifesaving benefit begins so early."
The recommended maximum doses in heart failure patients are carvedilol (Coreg) at 25 mg twice daily, or 50 mg twice daily for patients weighing more than 85 kg; 200 mg/day for extended-release metoprolol (Toprol XL); and 10 mg/day for bisoprolol (Zebeta). The three beta-blockers are similar in their efficacy for treating heart failure, Dr. Lindenfeld said. However, bisoprolol has the fewest pulmonary effects and is thus the best choice in patients with chronic obstructive pulmonary disease (COPD), even though it lacks a specific Food and Drug Administration (FDA)-approved indication for heart failure, she continued.
• Aldosterone antagonists: In terms of mortality benefit, the randomized trial data show that the aldosterone antagonists are nearly as good as beta-blockers. Yet they remain widely underutilized in the United States, according to Dr. Lindenfeld.