Icosapent Ethyl Cost-effective Compared With Standard Care: REDUCE-IT

Compared with standard care, using icosapent ethyl (Vascepa; Amarin) in patients with high cardiovascular risk whose triglyceride levels remain high despite statin therapy is a cost-effective strategy, according to a new analysis of the REDUCE-IT trial.

REDUCE-IT included 8,179 statin-treated patients who had controlled LDL cholesterol, persistently elevated triglycerides, and either established CVD or diabetes plus at least one additional risk factor. Both the original findings and a subsequent analysis showed reductions in MACE and total events of 25% and 31%, respectively, with icosapent ethyl 4 g/d versus placebo, and the US Food and Drug Administration expanded the drug’s indication in 2019.

While studies have shown the potential of icosapent ethyl to prevent CV events, some say it is priced too high and that patients aren’t always able to receive it.

What these results show, however, is that at an average price of $4-$6 per day, “we think that the drug provides good value,” lead author William S. Weintraub, MD (MedStar Washington Hospital Center, Washington DC), told TCTMD. “It's very safe. We prevent a lot of cardiovascular events. There's a slight increase in atrial fibrillation, slight increase in minor bleeding, but overall prevention of cardiovascular events, cardiovascular death, stroke, and myocardial infarction is so strong that appropriate patients really should be treated with this.”

Commenting on the study for TCTMD in an email, Fatima Rodriguez, MD, MPH (Stanford University School of Medicine, CA), said the results were good to see. “I think it is reasonable to conclude that icosapent ethyl is cost-effective for patients similar to the high-risk patients enrolled in the REDUCE-IT trial and when the cost of the drug is around $4/day. This is a negotiated drug cost and may not reflect what is happening across payers in the US.”

Meeting Benchmarks for Cost-effectiveness

For the analysis, published online Monday in JAMA Network Open, Weintraub and colleagues looked at the price of icosapent ethyl—$4.16 per day after rebates using SSR Health net cost (SSR) and $9.28 per day using the wholesale acquisition cost (WAC)—and event rates over the median 4.9-year follow-up period of the REDUCE-IT trial.

The study drug was associated with more quality adjusted life years (QALYs) than standard care both in the trial (3.34 vs 3.27) and projected over a lifetime (10.59 vs 10.35).

Within the trial, total health care costs were higher with icosapent ethyl both with the SSR cost ($18,786) or WAC ($24,544) compared with standard care ($17,273), with the cost per QALY gained being $22,311 using SSR and $107,218 using WAC. With lifetime projections, icosapent ethyl was expected to be cost-effective using SSR costs ($195,276) versus standard care ($197,064), but higher with WAC ($202,830).

At $4 per day, the probability of costing less with greater effectiveness was 58.4% over a lifetime with icosapent ethyl compared with standard care. Additionally, the researchers calculated 89.4% and 72.5% probabilities of costing less than $50,000 per QALY gained when using SSR cost and WAC, respectively.

“It was gratifying to find out that if [this is] what people really pay, it provides very good value,” Weintraub said. “Now what do people really pay for this? [If it’s] somewhere between $4 and $6 a day, it's very little to [pay] because you're preventing so many events.”

Acknowledging that some insurance companies have made it tough for patients to both receive and afford icosapent ethyl in the past, he said those hurdles are likely to ease in the near future. “I think you're going to find that the drug is going to become widely available for appropriate patients,” he said.

Costs of Finding Patients?

In an accompanying editorial, Dariush Mozaffarian, MD, DrPH (Tufts University, Boston, MA), writes, “Based on the most data-driven ‘in-trial’ estimates, icosapent ethyl appears to be a cost-effective treatment for patients who have hypertriglyceridemia and either existing CVD or diabetes and another risk factor.”

However, he notes several caveats. First, because the cost-effectiveness data was based on patients treated in 11 countries, there is the possibility that the results may not be generalizable to the United States.

Even so, Rodriguez notes, “the study findings are most pertinent to the US where drug pricing and other healthcare costs have a lot of variation (and are typically higher than other countries).”

A US-based cost analysis has already been presented as an abstract, Weintraub said, but a manuscript is expected to be published within the year showing that the drug is “even more cost-effective in the United States,” he noted.

Mozaffarian also points out that the study did not include costs related to incremental physician visits, screening, or laboratory testing, which would “not be trivial,” nor would they be the same as the costs of regular patient care outside of a trial. “Based on the additional costs of a few extra clinic visits and blood tests over a 4.9-year period, the cost-effectiveness of [icosapent ethyl] treatment is likely overestimated,” he cautioned.

Weintraub, however, said this concern is “completely” off-base, since previous analyses have shown no incremental follow-up costs associated with icosapent ethyl. Additionally, “we think that patients are going to be found incidentally when they have routine lipid screening, . . . so there's no cost in finding the patients,” he said. “Our findings are actually conservative, and he was just wrong about that. We were quite disappointed to see that in the editorial.”

Rodriguez sided with Weintraub. “Preventing cardiovascular events saves a lot of money, so the incremental costs of outpatient clinician visits and follow-up laboratory, although not considered in this analysis, are likely acceptable,” she said.

Regardless, Mozaffarian said that “containing the drug cost of icosapent ethyl at or below $4 per day is critical to maintain its cost-effectiveness as a treatment. At a time when Congress is actively debating the need for payers to have greater ability to negotiate prescription drug prices, this sensitivity of cost-effectiveness to drug price has particular salience, especially when pharmaceutical spending per capita in the US is already two- to three-fold higher than in other high-income countries.”

Rodriguez agreed, saying: “I hope that drug manufacturers for cardiovascular therapies consider the importance of value–the balance between clinical benefit and cost.”