This news release summarizes a study that estimated the benefits of sacubitril/valsartan (marketed as Entresto) vs enalapril (an ACE-inhibitor) in treating heart failure patients with lowered ejection fraction (the amount of blood pumped from the heart). In the study published in the medical journal JAMA Cardiology, researchers created a statistical model that estimated that about 28,000 patients per year with heart failure and a lowered ejection fraction could benefit from Entresto, a twice-daily pill approved in 2015. The model found that patients on Entresto lived a year longer, on average, than those treated with enalapril, and that the medication was “cost effective” when used with concurrent standard therapies. The release from the drugmaker, Novartis, describes their complex analysis and highlights their conclusion that the heart failure medication is cost effective. But the release does not include any discussion of the extremely high cost of the drug.
An estimated 6 million people in the United States have heart failure, and about half of those with heart failure also have reduced ejection fraction, so any treatment for them matters for their individual health and for society’s costs of overall health treatment. The release states that the analysis reinforces a strong recommendation from several medical societies that the condition be treated with sacubitril/valsartan. This release about the statistical model of effectiveness for the drug Entresto claims that it could delay or prevent thousands of deaths per year, but does not include analysis that the total cost of treating the majority of those eligible could drastically tax the health system. A 2015 story in Kaiser Health News reports on a nonprofit analysis that raised questions about the cost-effectiveness of Entresto.
The release mentions cost-effectiveness several times but does not give any indication of what the price of therapy with Entresto would be, nor the comparative cost between Entresto and other medications. Nor does it quantify what it means when it says the drug is “cost-effective.” The Institute for Clinical and Economic Review, ICER, warned in a draft report that the drug’s current price was too high and that widespread use could overwhelm the health system. The drug cost was estimated at about $4,600 per year for a typical patient. According to the report:
“At the list price of $4,560 per year, Entresto does not save money over the long term but its added costs are well-aligned with the degree of benefit it brings to patients, meaning that Entresto can be judged “cost-effective” in the long-term according to commonly accepted cost-effectiveness thresholds.”
“However, ICER’s analysis predicts that nearly 2 million patients could be prescribed Entresto over the first five years, creating a total budget impact so high that excessive cost burdens would be placed on the overall health care system. In order to keep health care cost growth in line with growth in the national economy, ICER’s value-based price benchmark for Entresto is $3,779 annually, a 17% discount off the list price. Private insurers and Medicaid programs are frequently able to achieve discounts at this level.”
The published study did address cost in terms of quality-adjusted life-years (QALYs). It would have been helpful for the release to add at least some costs which would add context.
The release makes several statements about benefits to an entire population, not necessarily the benefits to an individual patient. The release provides a useful number-needed-to-treat explanation.
“For every 1,000 patients treated with Entresto vs. enalapril, potentially 59.7 HF hospital admissions could be averted per each year alive in the model.3 In addition, Entresto increased life expectancy at an incremental cost-effectiveness ratio consistent with other high-value widely accepted cardiovascular interventions such as implantable cardioverter defibrillators (ICDs) and cholesterol-lowering statins before they became generic.3″
One weakness in describing the benefits was the omission in the release (but not in the published study) of actual figures or percentages to back up the cost-effectiveness claim.
The release includes extensive information on harms, including this summary of side effects: “Entresto may cause serious side effects including serious allergic reactions causing swelling of the face, lips, tongue, and throat (angioedema) that may cause trouble breathing and death.”
The release provides some detail on the statistical model used and the analysis findings. Data was drawn from a previous trial to model health outcomes and cost-effectiveness of the drug over a 30-year period.
The release would have been stronger with a discussion of possible limitations of the analysis. Patients out in the real world tend to be older, sicker, and have other differences compared with those who participate in clinical trials, so it’s not clear that the benefits seen in the trial can be extrapolated to the broader population. In the study itself, the researchers mention several issues that could throw their findings off, but the release doesn’t address them.
There is no disease mongering.
The news release is coming from the manufacturer of the drug, Entresto, so the conflict of interest is clear. However, we would have liked it better if the release had identified, as the study did, that the principal author of the study receives grant support from Novartis, and several other authors are employees of Novartis.
Entresto was compared to enalapril and found to be associated with — on average — a year longer of survival as well as reduced hospital admissions.
It’s noted that the drug is FDA approved.
The release states that this analysis is not the first, but is novel because it quantifies “possible” impact in reducing death.
“This analysis, based on an application of the results of PARADIGM-HF to published heart failure statistics, is the first to quantify the possible impact of Entresto’s potential benefit in reducing death.1″
There was no unjustifiable language.