New Treatments, New Legislation Bring Change to the HF Landscape
Two new drugs approved for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) and emerging technologies for smaller, more durable ventricular assist devices (VADs) for patients with advanced HF are changing the landscape of managing HF. Strategies to remotely monitor pulmonary congestion for earlier detection to prevent HF hospitalization (HFH), such as the implantable CardioMEMS device are being pursued. Together these advances are providing new tools to address the challenge of HFH and reduce mortality in an expanding HF population.
Entresto, the combination of sacubitril and valsartan, is the biggest advance in the last several years, says Mary Norine Walsh, MD, FACC, vice president of the ACC. Shown to be superior to best standard of care, the reduction in cardiovascular mortality and HFH with Entresto in the well-conducted PARADIGM-HF trial truly represents a paradigm shift, with the potential to improve care in many HF patients. This first-in-class drug, approved by the U.S. Food and Drug Administration (FDA) in July 2015, was shown to improve median survival by 1.5 years in a recent analysis of patients in the pivotal study, a substantial life extension for a condition that has a median survival of five years from its diagnosis.
Careful attention must be paid to the side effect profile of Entresto, particularly angioedema, as physicians consider moving their patient from the cornerstone treatment of angiotensin-converter enzyme inhibitors and angiotensin-receptor blockers to the angiotensin-receptor/neprilysin inhibitor combination. Cost will be another consideration, with patients and payers weighing in on the move from a generic to a nongeneric drug.
Corlanor (ivabradine), approved by the FDA in April 2015 for patients with HFrEF who are in sinus rhythm and have a heart rate >70 bpm, slows heart rate, but has few if any other cardiovascular effects. In the SHIFT trial, the reduction in HFH was the primary driver of the reduction in the combined endpoint of HFH and cardiovascular death with Corlanor. For patients unable to tolerate a beta-blocker, Corlanor provides a new treatment option.
“These are important drug advances for HFrEF, which carries a high baseline morbidity and mortality, with a high burden of HFH on our health care system,” says Christopher O’Connor, MD, FACC, editor-in-chief of JACC: Heart Failure. The coverage of cardiac rehabilitation by the Centers for Medicare and Medicaid Services is another important advancement. Shown to reduce HFH and improve quality of life in patients with HFrEF in the HF-ACTION study led by O’Connor, cardiac rehabilitation was assigned a Class Ia recommendation in the ACC/American Heart Association HF guidelines.
The miniaturization of VADs for patients with advanced, stage D HF is a major advance, and their use as destination therapy as a permanent alternative to heart transplant likely will continue to grow as more VADs are approved. Ultimately, in perhaps a decade, VADs that are sufficiently small enough, including the power source, to be fully implanted similar to a cardiac resynchronization device, will open the door to many more patients, says Walsh. The current generation of VADs require less surgical dissection, and other surgical approaches to further reduce this burden are being investigated, such as a lateral thoracotomy in the HVAD LATERAL trial.
Meaningful improvements in mid-term survival (median survival four years) and quality of life have been provided by the first continuous flow VAD approved for destination therapy, HeartMate II, for patients who otherwise face a very poor chance of survival, says Sean Patrick Pinney, MD, FACC. HeartMate 3 was recently shown to have a six-month survival of 92 percent in 50 patients and to improve quality of life and functional status in a European study comparing them with historical controls in the HeartMate II registry. The first results with HeartMate 3 in the U.S. are anticipated in early 2017 from the MOMENTUM 3 study. Results are awaited from the ENDURANCE Supplemental trial of the HeartWare device for its approval as destination therapy. The ENDURANCE trial had shown HeartWare was noninferior to any FDA-approved device for destination therapy.
Also expected to be reported soon is the PAL-HF disease management study of palliative care in very advanced HF, with the predominant goal of identifying strategies to improve quality of life, regardless of mortality risk. O’Connor is also a co-investigator of this National Institutes of Health-funded study. In the HFpEF arena, “there has been no big win yet,” says Walsh. Notably, the NEAT trial demonstrated that nitrates are contraindicated in HFpEF patients, with physical activity lower and side effects higher with nitrates. The PARAGON-HF trial is examining Entresto in HFpEF, and is expected to wrap up in 2019. Signals from a Swedish registry and the TOPCAT trial suggest that neurohormonal activation may drive outcomes in HFpEF, too, says Pinney.
The move to value-based care requires more effective home-based disease management strategies. With the objective of reducing HFH, implantable and noninvasive devices are being investigated to monitor pulmonary congestion to provide actionable data for altering treatment earlier. The FDA-approved CardioMEMS pulmonary artery pressure monitor reduced HFH and rehospitalization at six months in the CHAMPION trial. However, realizing the potential of these devices requires a robust HF disease management program with a clinician dedicated to monitoring the data and making treatment decisions.
The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) legislation is crucial and will have a direct impact on the care of HF, says Walsh, benefiting patients, clinicians and health care systems. Physician-directed, nurse-managed, value-based care will be more effectively delivered under a system that does not require a fee for individual components of care that require a lot of time and focus from the health care team.
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