Indeed, three major randomized trials showed roughly a 25% reduction in total mortality, compared with placebo, in patients on standard background therapy including a beta-blocker and ACE inhibitor, along with a 20% decrease in risk of sudden cardiac death. The doses used were spironolactone at 12.5-25 mg/day or eplerenone (Inspra) at 25-50 mg/day.
An intriguing retrospective analysis conducted in close to 7,000 patients with heart failure following an acute myocardial infarction concluded that getting the aldosterone antagonist onboard early in that situation is key. Patients who started on the drug less than 7 days post MI had a 29% reduction in total mortality and a 47% decrease in sudden cardiac death, compared with those started on day 7 or later (Eur. J. Heart Fail. 2009;11:1099-1105). That benefit is believed to be the result of early left ventricular remodeling.
A definitive European prospective, randomized trial looking at the impact of starting an aldosterone antagonist within 7 days after acute MI is due to be presented later this year. The inside word is the results are highly favorable, she noted.
Hyperkalemia is a legitimate concern when prescribing an aldosterone antagonist. These agents should be avoided in a patient who has a creatinine level above 2.5 mg/dL or an estimated glomerular filtration rate below 30 mL/min per 1.73 m2, or if other potassium-sparing drugs are onboard. Potassium levels should be checked after the first 3-7 days of therapy, again at 1 month, and then every 3 months, as well as anytime a patient becomes dehydrated.
• Digoxin: In the classic digoxin trial involving close to 7,000 patients, heart failure hospitalization was a prospectively defined endpoint. In patients with a left ventricular ejection fraction of 25%-45%, hospital admission for heart failure was reduced by 26% in patients assigned to digoxin. In those whose ejection fraction was less than 25%, the reduction in hospitalization was 39%.
"So don’t forget that digoxin is still a good drug in patients with low ejection fraction or who have substantial symptoms," Dr. Lindenfeld said. "If we had a drug approved today that didn’t change mortality but reduced hospital admissions by 39%, we’d all be giving it – and we’d be paying a lot for it."
• Role of iron deficiency in heart failure: A new European study is illuminating on this score: Among a cohort of 1,506 patients with chronic heart failure, fully 50% were determined to have iron deficiency, as defined by a ferritin level less than 100 mcg/L, or a ferritin level of 100-299 mcg/L with a transferring saturation lower than 20%. In a multivariate regression analysis, iron deficiency was a strong independent predictor for mortality, associated with a 42% increased risk (Am. Heart J. 2013;165:575-82).
"I think if you restricted the study to hospitalized heart failure patients, the iron deficiency rate would be even higher. It’s just appalling how many people we send home iron deficient without iron replacement therapy," Dr. Lindenfeld asserted.
She noted that in the European FAIR-HF trial involving 459 hospitalized iron-deficient heart failure patients randomized at discharge to intravenous iron corrective and maintenance therapy or to a matching placebo, the iron replacement group demonstrated significant improvement in quality of life and exercise capacity. The benefits were seen regardless of whether a patient’s baseline hemoglobin was high or low.
In addition, the rate of the combined endpoint of first hospitalization for worsening heart failure or death was 7.5% in the iron recipients, compared with 13.9% in placebo-treated controls – a difference that didn’t achieve statistical significance because the study was underpowered to evaluated that endpoint (N. Engl. J. Med. 2009;36:2436-48).
"Iron replacement is a distinct advantage for these patients, so you should be looking for iron deficiency. You probably don’t need to use IV iron, but if your patient is in the hospital anyway, IV iron is pretty benign and will get him iron-repleted almost immediately," Dr. Lindenfeld continued.
Before sending iron-deficient patients home on oral iron, make sure they can absorb it. Many older individuals can’t. Indeed, among patients hospitalized at the University of Colorado heart failure service, only 13% can actually absorb oral iron, she explained.
A simple way to tell is to draw a serum iron level, give the patient an iron tablet, and check the serum iron level again in 1-3 hours. It should roughly double, Dr. Lindenfeld explained.
Dr. Lindenfeld reported serving as a consultant for Medtronic, St. Jude, and other companies.
*Correction, 8/12/2013: An earlier version of this story misstated the meaning of ACE.