Drug Approvals Provide New Options for Treating Heart Failure
2015 saw the first two approvals of new heart failure drugs in a decade. Here’s how a Cleveland Clinic heart failure expert sees the new agents fitting into the mix of options.
Earlier this year, the U.S. Food and Drug Administration approved two new drugs that provide the first new options in a decade in treating chronic heart failure.
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Heart failure affects about 5.1 million Americans, according to the FDA, and is a leading cause of death and disability. Sacubitril/valsartan (Entresto®; formerly known as LCZ696) and ivabradine (Corlanor®) are the first new heart medications on the market in almost 10 years, providing hope in the fight against an obstinate disease.
Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor that improves blood flow by widening the arteries while also lowering the volume of fluid in the body. The FDA approved the combination agent, the first commercially available therapy to act by neprilysin inhibition, in summer 2015. Sacubitril/valsartan is indicated for patients who have chronic stable heart failure with reduced ejection fraction. It’s an option for all patients with heart failure and an ejection fraction of less than 40 percent who previously tolerated a standard dose of angiotensin-converting enzyme (ACE) inhibitor therapy, says Randall Starling, MD, MPH, Medical Director of Cleveland Clinic’s Kaufman Center for Heart Failure.
Dr. Starling was the U.S. leader of the steering committee of the 8,400-patient phase 3 PARADIGM clinical trial that formed much of the basis of the agent’s approval, and Cleveland Clinic was a participating center. That trial was stopped early due to better-than-expected results in reducing mortality and hospitalization in heart failure patients with reduced ejection fraction.
Dr. Starling says the drug can be provided to a wide spectrum of patients on an outpatient basis with close blood pressure monitoring. In general, patients need to have a systolic blood pressure over 100-110 mm Hg. “Sacubitril/valsartan offers incremental benefits beyond our existing treatments, such as beta blockers and enalapril, by reducing hospitalizations and mortality,” he notes.
This new combination agent is administered orally in tablet form. Its most notable side effect is a risk of hypotension, with other side effects including risk of hyperkalemia and kidney function complications.
Ivabradine was approved by the FDA in spring 2015. It works by inhibiting the l(f) current in the sinoatrial node to slow the heart rate without affecting ventricular repolarization or myocardial contractility.
Its use is limited to chronic systolic heart failure patients on guideline-directed medical therapy, including beta blockers, who have a resting heart rate over 70 beats per minute. Patients who do not tolerate beta blockers can be treated with ivabradine with a goal of lowering the heart rate.
Dr. Starling says ivabradine has the ability to reduce hospital readmissions. Studies have shown the drug can decrease the risk of hospitalization and cardiovascular death by 18 percent for patients with worsening heart failure.
Previous drug therapies not only slow the heart rate, but also lower blood pressure. Ivabradine is indicated as an add-on therapy to reduce risk of hospitalization in patients with stable symptomatic chronic heart failure.
Ivabradine is taken orally twice daily. Its most common side effects in clinical trials — bradycardia, atrial fibrillation, increased blood pressure and vision changes—were reversible by lowering the dose.
For both new therapies, patients are started on the lowest of three doses with levels up-titrated after a follow-up visit with their heart failure specialist.