Borderline Cost-effectiveness for SGLT2 Inhibitors in HFpEF

If the cost of the drugs can be lowered, however, they would shift into the high-value category, the analysis shows.

Borderline Cost-effectiveness for SGLT2 Inhibitors in HFpEF

Adding sodium-glucose cotransporter 2 (SGLT2) inhibitors to standard medical therapy for heart failure with preserved ejection fraction (HFpEF) provides just low-to-intermediate economic value to the healthcare system, a cost-effectiveness analysis indicates.

And that’s assuming at least a small reduction in the risk of cardiovascular mortality with the agents, which did not demonstrate a significant reduction in that endpoint in pivotal trials. Use of SGLT2 inhibitors would not be considered cost-effective at all without a survival benefit.

On the other hand, lowering the cost of using the drugs—currently $4,000 a year or more—would shift them into the high-value category, researchers led by Laura Cohen, MD (Massachusetts General Hospital, Boston, MA), report in a study published online recently in JAMA Cardiology. Cohen also presented the results as a poster at the recent American College of Cardiology/World Congress of Cardiology (ACC/WCC) 2023 meeting.

These findings should not be used to influence decisions around use of SGLT2 inhibitors for individual patients with HFpEF, Cohen told TCTMD. “Obviously we think about cost when we’re thinking about prescribing drugs, and we’re thinking about the individuals, but this type of analysis is really looking more from an economic or societal perspective,” she said.

It’s not surprising that these medications look less attractive from a cost-effectiveness perspective for patients with HFpEF than for those with heart failure with reduced ejection fraction (HFrEF), because there was a clearer mortality benefit in the HFrEF trials, Cohen said. What’s more surprising, she added, is that even with the lesser impact on CV mortality and the high cost of the drugs, they remained in the “intermediate-value” range.

But regardless of the cost-effectiveness, it remains important to at least try SGLT2 inhibitors in patients with HFpEF who are good candidates, Cohen said, noting that “these are the only drugs that have shown a proven benefit in randomized controlled trials in improving cardiovascular outcomes” in this population.

Dhruv Kazi, MD (Beth Israel Deaconess Medical Center, Boston, MA), one of the senior authors of the paper, agreed. “I still think the patients who do qualify for SGLT2 inhibitors should be on it, [as] it’s the only therapy for which we have very clear evidence” in HFpEF, he told TCTMD. He added, “It’s really important that cost-effectiveness analyses not be used for individual-level decision-making.”

The implications are more at the level of healthcare systems, Kazi said. “The way I’m thinking about it is that there is a need for the system to do a better job at price control for these drugs or price negotiations for these drugs,” he said, because the estimates of cost-effectiveness were very sensitive to the annual cost.

An Economic Look

The SGLT2 inhibitors empagliflozin (Jardiance; Boehringer Ingelheim/Eli Lilly) and dapagliflozin (Farxiga; AstraZeneca) both demonstrated significant improvements in clinical outcomes for patients with HFpEF in their respective trials, EMPEROR-Preserved and DELIVER, with the benefits driven by reductions in heart failure hospitalizations.

In the US Medicare population alone, there are roughly 3 million people with HFpEF, and that number is on the rise, Kazi noted. “This is a promising therapy that is going to be useful for a lot of individuals, and so the cost-effectiveness and budget impact of that medication becomes immediately policy relevant,” he said.

Cohen, Kazi, and colleagues dug into this question by simulating monthly health outcomes and direct medical costs associated with adding SGLT2 inhibitors to standard HFpEF therapies. They used data from the published literature—including a meta-analysis of the EMPEROR-Preserved and DELIVER trials—and other publicly available sources. The base-case annual cost was set at $4,506.

The addition of SGLT2 inhibitors was projected to reduce the mean number of lifetime heart failure hospitalizations and to increase survival, with a rise in lifetime quality-adjusted life-years (QALYs) from 5.27 to 5.46.

That bump in QALYs came at the cost of $26,312 in direct health spending compared with standard care, resulting in an incremental cost-effectiveness ratio (ICER) of $141,200 per QALY gained. That falls in the intermediate range of the value framework established by the ACC and the American Heart Association, in which an ICER below $50,000 represents high value, from $50,000 to < $150,000 represents intermediate value, and $150,000 or higher represents low value.

In most of the simulations (59.1%), the addition of SGLT2 inhibitors had intermediate value, and in the rest, they had low value.

Cost-effectiveness was most sensitive to the effects on CV death and to the costs of the drugs. The analyses assumed a 12% relative reduction in CV death (HR 0.88), and when the HR went higher—ie, less beneficial effect—the addition of SGLT2 inhibitors became a low-value approach. Assuming no effect on mortality, the ICER ballooned to $373,400 per QALY gained.

As for cost, use of SGLT2 inhibitors would represent high value if the annual price of the drugs could be cut to below $1,431—which might be reasonable once generics are available, the authors say—and low value if the annual price would exceed $4,795.

From a broader perspective, US healthcare spending would increase by $4.3 billion if all eligible adults with HFpEF were started on SGLT2 inhibitors in addition to their standard therapies, accounting for $4.8 billion in new drug spending and $500 million in savings from avoided CV hospitalizations.

“The cost-effectiveness findings should be interpreted in the context that SGLT2 inhibitors are the first pharmaceutical class to meet primary endpoints in randomized clinical trials of patients with HFpEF, and the Class 2a recommendation in the recent HF guidelines is likely to be upgraded in the future given the recent positive trial results,” the investigators write.

‘Improving Outcomes in HFpEF Patients Is Hard’

Commenting for TCTMD via email, Alexander Sandhu, MD (Stanford University and Palo Alto VA Medical Center, CA), who wrote an accompanying editorial with David Cohen, MD (St. Francis Hospital and Heart Center, Roslyn, NY), said the findings of this analysis are generally consistent with a similar one focused on empagliflozin published last year in JAMA Internal Medicine.

He pointed out that there are some differences between the general HFpEF population and the participants in EMPEROR-Preserved and DELIVER that could color the interpretation of cost-effectiveness in everyday practice. In particular, real-world patients tend to be sicker, with higher rates of chronic kidney disease (CKD), worse health status, and greater risks of hospitalization and death.

“Each of these factors may increase the magnitude of clinical benefit observed with SGLT2 inhibitor use in general practice compared with the trial populations,” Sandhu said. “On the other hand, patients in clinical practice are often older with more comorbidities that increase their risk of noncardiovascular death, which would be expected to lower the absolute benefit of therapy because they may die before reaping the cardiovascular benefits of therapy. So how the therapy effectiveness seen in these trials would translate to clinical benefit and cost-effectiveness in a general practice population remains an important question.”

But in agreement with Cohen and Kazi, Sandhu said that cost-effectiveness analyses, though they can provide information on the average magnitude of clinical benefits, should not be used to guide decision-making on an individual level.

“Most HFpEF patients would benefit from being on SGLT2 inhibitors, the only current therapy demonstrated to improve clinical outcomes and health status,” he said, noting that patients with CKD and those who are more symptomatic are likely to derive even greater benefits. “So I’ve been especially focusing on promoting uptake among those populations in my own practice. But I think it is really a matter of shared decision-making, helping patients understand the expected benefit and their out-of-pocket costs to make the decision whether the treatment is valuable to them.”

Assessing cost-effectiveness “helps us think about priorities for investing in implementation and uptake,” Sandhu said. “This analysis does suggest increasing uptake at current costs for some payers is likely not high value. It is worth noting that there is substantial cost variation across payers. Many payers likely purchase SGLT2 inhibitors at a cost that would be substantially higher value.”

Kazi noted that there are some changes in the works that may make SGLT2 inhibitors more cost-effective in the coming years. He pointed to parts of the Inflation Reduction Act, which was signed into law last year, that are aimed at controlling drug costs through negotiation of the prices of top-selling medications, limiting price increases so they cannot exceed rises in inflation, and capping out-of-pocket costs at $2,000 per year.

“I’m hoping that more patients will be able to afford the comprehensive guideline-directed therapy they need,” he said. “At the same time, [I recognize] that a $2,000 out-of-pocket cap is still fairly high and many patients will still be priced out of these lifesaving therapies if we’re not cautious about how we use them.”

For Sandhu, these types of analyses “emphasize improving outcomes in HFpEF patients is hard.” He added that “it remains a challenge for us in the heart failure community to find additional interventions that can improve outcomes in this challenging population.”

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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  • Laura Cohen and Kazi report no relevant conflicts of interest.
  • David Cohen reports grants from Edwards Lifesciences, Abbott, Boston Scientific, Corcinch, Zoll Medical, Philips, iRhythm, Medtronic, and Corvia and personal fees from Edwards Lifesciences, Medtronic, Abbott, Boston Scientific, Corvia, and Bristol Myers Squibb outside the submitted work.
  • Sandhu reports support from the National Heart, Lung, and Blood Institute.