Recently published guidelines for the pharmacologic management of heart failure in patients with reduced ejection fraction (HFrEF) focus on two drugs – both of which have been approved by the Food and Drug Administration – that have shown promise in managing heart failure patients.
The guideline committee has deemed that the combination drug sacubitril-valsartan (Entresto, Novartis) and ivabradine (Corlanor, Amgen) as “milestone” achievements. In this reader’s mind, compared with the mortality and morbidity effect of beta-blockers and ACE inhibitors, they really don’t make it to that status. They do, however, reach the threshold of important adjuncts to the care for heart failure treatment.
Ivabradine was shown to improve the combination of rehospitalization and mortality when added to conventional therapy, including beta-blockers, by decreasing heart rate. Unfortunately, many of the patients in the trial were not adequately treated with beta-blockers. Sacubitril-valsartan, a drug we have commented about in previous columns, is interesting and adds an additional effect on mortality and morbidity when compared with enalapril alone. In the PARADIGM-HF trial, it showed a significant 20% decrease in rehospitalization and total mortality. A strong case can be made that it should be used instead of an ACE inhibitor, although it is associated with some increased hypotension and angioneurotic edema.
Sacubitril-valsartan poses a significant social issue in regard to its pricing. Most of the drugs we use for the treatment of heart failure cost less than a dollar a day when introduced, and pennies now, and they are immensely effective. Sacubitril-valsartan on average moves the mortality needle a bit, but at a cost of 20 times its competitor, enalapril. It doesn’t do it in all patients, so that it might be reasonable to use it just in those patients who are failing with an ACE inhibitor alone. This is the first time heart failure doctors have had to grapple with the problem of drug pricing, whereas the oncologist and the lipid specialists have been facing this issue for some time. Is it worth $500 a month, compared to $25 a month, to possibly move the mortality index, which has already been modified with the previous ACE inhibitors, down a bit? I suppose that the decision is up to all of us to make.
Reading the guidelines, however, provided me with some insight that I have missed in the past. Of the 17 members of the guideline writing team representing the American College of Cardiology, American Heart Association, and the Heart Failure Society of America, eight had “significant relationships” with the two pharmaceutical companies in question. Committee members were advised not to vote if they had a relevant relationship with industry. How they functioned in the committee proceeding it’s impossible to tell, but the potential for bias is there. I would imagine that eight other heart failure specialists who did not have a conflict could have been found to serve on the writing committee. As guidelines have become such a major part of the construct of the pharmacopoeia, potential bias like this should and easily can be avoided.
Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.