ORLANDO – The combined formulation of sacubitril and valsartan substantially cut the rate of 30-day heart failure rehospitalizations, trimming the control rate by 38% in an analysis of data from the PARADIGM-HF trial, Dr. Scott D. Solomon reported at the American Heart Association scientific sessions.
This is an especially meaningful additional benefit for heart failure patients who take sacubitril/valsartan (Entresto) in place of enalapril or similar drugs because heart failure rehospitalizations have become a closely tracked metric for U.S. hospitals.
Dr. Scott D. Solomon
The sacubitril/valsartan combination received Food and Drug Administration approval last summer for treating chronic heart failure with reduced ejection fraction on the strength of results from PARADIGM-HF, which showed the two-drug combination substantially cut the rate of cardiovascular death and heart failure hospitalizations, compared with enalapril (N Engl J Med. 2014 Sep 11;371:993-1004).
“The data suggest that chronic heart failure patients treated with sacubitril/valsartan relative to enalapril are less likely to be initially hospitalized, and subsequent to discharge are less likely to return to the hospital within 30 days, thereby reducing the risk to patients and the potential financial burden to the health care system,” said Dr. Solomon, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital in Boston.
This finding may help spur faster adoption of sacubitril/valsartan as the top drug for treating the renin-angiotensin-aldosterone system in heart failure patients, commented Dr. Adrian F. Hernandez, professor and heart failure specialist at Duke University in Durham, N.C. “The fact that you can derive an early clinical benefit” that becomes an early financial benefit should help counter the higher cost for sacubitril/valsartan, compared with generic ACE inhibitors and angiotensin-receptor blockers, he said in an interview. Health system administrators “face an issue when they can only look at long-term horizons. But data like these, with the early benefit of reduced readmissions” make it easier to justify paying a higher drug cost. Health care systems increasingly focus on treatments that can produce rapid benefits, both clinically and financially, said Dr. Hernandez, director of health services and outcomes research at Duke.
Dr. Adrian F. Hernandez
In fact, a cost-effectiveness analysis of sacubitril/valsartan treatment in PARADIGM-HF that included the hospital readmissions data showed that the combined formulation was “highly cost effective,” compared with enalapril, said Dr. Solomon, who added that he and his associates will have a full report on this in 2016.
“Not only does sacubitril/valsartan reduce mortality and hospital admissions, but it also reduced readmissions. That is very exciting. This is one of the few treatments to have this effect”, commented Dr. Jennifer Thibodeau, medical director of the heart failure disease management program at the University of Texas Southwestern Medical Center in Dallas. The 38% reduction in total heart failure readmissions, compared with enalapril, and the 44% reduction in number of patients with a 30-day readmission was “pretty good,” she said in an interview. “Anything that could reduce readmissions that much is pretty good.” Plus, clinicians have already been quite excited about sacubitril/valsartan based on the primary-endpoint benefits it showed in PARADIGM-HF, “although there is always caution when a drug is brand new,” she added.
Dr. Jennifer Thibodeau
Since U.S. marketing for sacubitril/valsartan began last summer, “there has not been a big rush to adopt it,” primarily out of the usual concerns about new agents. “As we continue to see findings like these [reduced readmissions], there will be [substantial] adoption of this drug. The new findings definitely add to its attraction.” Dr. Thibodeau said.
The two subgroups of patients who had heart failure hospitalizations in PARADIGM-HF, the 675 patients in the sacubitril/valsartan arm and the 775 in the enalapril arm, closely matched each other for virtually all demographic and clinical parameters aside from history of atrial fibrillation, which was significantly more common in the enalapril patients. Even though these two subgroups had not been randomized, the near uniform consistency of their profiles made this “a valid analysis,” Dr. Solomon said. Overall, 20% of the PARADIGM-HF patients who had a heart failure hospitalization had a rehospitalization for any cause within 30 days.
The 30-day heart failure readmission rate was 10% among patients on sacubitril/valsartan and 13% among those on enalapril, a 38% relative risk reduction that was statistically significant. The number of patients with a heart failure readmission was 44% lower in the group on the combined formulation. After 60 days, readmissions for any cause were 23% lower in the sacubitril/valsartan arm, compared with enalapril, and the combined formulation dropped the number with any 60-day readmission by 30%, he reported.