Digitalis revisited

Still helpful, after all these years

Digitalis has a longer clinical history than the stethoscope. But its role in treating heart failure wasn’t formally defined until about two years ago.

"Didge’ is a great story," says Americo Simonini, MD, cardiologist at Cedars-Sinai Medical Center in Los Angeles. For hundreds of years, everyone knew it could help CHF patients; stories recounting how a woman’s CHF symptoms were eased after she chewed foxglove leaves are nearly legendary. But from that point, experts say it was good enough to know digitalis could help. Details — such as how much was most effective or how it affected survival — went unstudied.

"No one really did a randomized study until the multicenter DIG trial," he says. Doctors knew it was helpful for controlling arrhythmia and increasing exercise performance but didn’t really get the specifics until 1997, when the Digitalis Investigation Group (DIG) published its report in the New England Journal of Medicine. This trial showed:

• Digitalis, or digoxin, had no effect on patient survival.
• It did reduce CHF hospitalization by 28% and general hospitalizations by 6%.

Digoxin’s defined role is to help patients deal with the effects of their disease — even when they are being maintained on complex schedules of diuretics, ACE inhibitors, and beta-blockers.

"People on maximal therapy can also benefit symptomatically from digoxin," says Stephen S. Gottlieb, MD, a cardiologist at the University of Maryland in Baltimore and one of the 150 authors of the ACTION HF guidelines for treating heart failure, published in the American Journal of Cardiology in January.

Everyone with symptoms’ should take it

"Everyone with symptoms of heart failure should be on digoxin," adds Simonini. Just look at the DIG trial, he says. There was less pump failure, improved quality of life, and reduced hospitalization. "That’s not a bad deal for a drug so cheap, it’s a generic."

So while ACE inhibitors and beta-blockers get a lot of press about their ability to lower patient mortality, digoxin still makes the list of recommended drugs because it improves a patient’s quality of life, although it doesn’t add any more days to it.

"It’s quality of life rather than quantity of life," says David Roffman, PharmD, BCPS, associate professor at the University of Maryland’s School of Pharmacy. "Digoxin is dumped down to a lower rung of increasing exercise tolerance."

Consider however, for patients over 65, CHF is the No. 1 cause of hospitalization and rehospitalization, notes Emmanuel Saltiel, PharmD, clinical pharmacist at Cedars-Sinai. Digoxin can reduce those numbers. "That’s not a trivial outcome."

Roffman, who is also a CCU therapeutic consultant, says that as an inotropic agent, digoxin is used to increase the muscular contractility of the heart. The better squeeze increases cardiac output, so patients can do things such as walk longer without symptoms.

"It’s tempting to make that leap of faith that it will improve survivability," Roffman says. In fact, no inotropic has been shown to improve survival of CHF patients. Several drugs have been shown to do the opposite — they were found to increase mortality, he says. In testing the hypothesis of the stronger inotropic improving survival, the opposite was true — the stronger the agent, the shorter the survival. Here are some of the drugs and the studies that were done with them:

• Milrinone: Packer M, et al. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991; 325:1,468.

• Vesnarinone: Cohn J, et al. A dose-dependent increase in mortality with Vesnarinone among patients with severe heart failure. N Engl J Med 1998; 339:1,810-1,816.

Other drugs such as Flosequinan and Manoplax had similar findings.