SAN DIEGO — With no medical therapy, patients with stage C and D heart failure face a 2-year mortality risk of 35%, Lee Goldberg, M.D., said at the 100th International Conference of the American Thoracic Society.
But clinicians can reduce the 2-year mortality in this population of patients by 12%–24% if they treat patients with the available medical therapies.
“The number needed to treat to save one life is four patients,” said Dr. Goldberg of the heart failure/transplant program at the University of Pennsylvania Health System, Philadelphia.
“So it's extremely cost effective to treat heart failure patients. Many of the medical therapies we have are underutilized—especially in patients who are less symptomatic,” Dr. Goldberg said.
He reviewed the following treatments, commonly used in patients with stage C and D heart failure:
▸ Diuretics. Although there are no clinical trial data proving their efficacy in this patient population, diuretics are the most commonly prescribed drugs for patients with advanced heart failure.
“But we know from epidemiologic data that diuretics don't change the natural history of heart failure,” Dr. Goldberg said. “Morbidity and mortality after taking them doesn't change very much.”
Loop diuretics are the most commonly used type, although many centers use thiazide diuretics in combination to augment the effects of loop diuretics.
“I would titrate to signs and symptoms of volume overload,” he advised. “Many disease management programs have action plans of sliding-scale diuretics to help patients control their volume status. It keeps them out of the hospital and keeps them safe, but it doesn't prolong their life, and it doesn't change the [heart] remodeling process.”
The symptomatic benefits of diuretics occur more rapidly than those of other drugs, and diuretics are the only class of drugs that adequately control chronic fluid retention. Adverse effects may include volume depletion and renal insufficiency. Metabolic effects may include electrolyte imbalance, hyperuricemia, and hyperglycemia.
There are lingering questions about this approach, however: Will newer agents replace the loop diuretics? Which are the best combinations? “These questions still need to be studied,” he said.
▸ ACE inhibitors. There are “buckets of data” on the use of these agents in advanced heart failure. ACE inhibitors interfere with the renin-angiotensin system and enhance the action of kinins. “They alleviate symptoms, reduce death, and reduce hospitalizations,” Dr. Goldberg said. “So they hit all three of our goals [in treating these patients]: heart remodeling, symptoms, and mortality.”
These drugs are typically given to all patients with systolic dysfunction. “A lot of people believe they should also be used in diastolic dysfunction, but we don't have good data for that yet,” he said.
Adverse effects may include hypotension, azotemia, hyperkalemia, cough, and angioedema. Unanswered questions include whether there is a class effect. “The answer is probably yes,” he said. Also, it is not known whether there is a significant interaction with aspirin. “Most of us are comfortable using both aspirin and ACE inhibitors,” said Dr. Goldberg, also of the University of Pennsylvania.
▸ β-Blockers. These drugs inhibit the adverse effects of the sympathetic system, and they delay and reverse heart remodeling. “The No. 1 way to increase the ejection fraction in patients with heart failure is to actually put them on a β-blocker,” Dr. Goldberg said.
β-Blockers are currently given to all patients with systolic heart failure in the absence of fluid overload. Adverse effects may include hypotension, bradycardia, and worsening heart failure.
The ideal target dose for β-blockers has not been determined. This is one remaining question about this class of drugs. “There is probably not a class effect,” he said. “It appears that the long-acting β-blockers and nonselective β-blockers may have an advantage over the shorter-acting and selective ones.”
▸ Angiotensin II receptor blockers. These drugs block the effect of angiotensin II at the receptor site. They delay heart remodeling and reduce symptoms, and they have been shown to reduce hospitalizations and deaths.
ARBs are currently given to patients who can't tolerate ACE inhibitors—specifically, the side effects of angioedema and cough.
The Valsartan Heart Failure Trial (Val-HeFT) and the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) trial showed some improvement in the efficacy of ARBs when used with ACE inhibitors. However, patients in the Val-HeFT trial who took ARBs with an ACE inhibitor and a β-blocker had worse outcomes. This association was not found in the CHARM trial.
Adverse effects may include hypotension, azotemia, hyperkalemia, and cough.
Will ARBs ever replace ACE inhibitors? That's a key question about this class of drugs, Dr. Goldberg said.