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Treating acute coronary syndromes (ACS) patients with ticagrelor rather than clopidogrel for 12 months is clearly a cost-effective strategy, according to a health-economic substudy of the PLATO trial published online June 19, 2012, ahead of print in the European Heart Journal.

PLATO (PLATelet Inhibition and Patient Outcomes) randomized 18,624 ACS patients to aspirin plus ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). Results showed that the potent direct P2Y12 receptor antagonist reduces the rate of the primary composite of cardiovascular death, MI, or stroke as well as all-cause death without increasing overall major bleeding.

For the substudy, investigators led by Elisabet Nikolic, of Linköping University (Linköping, Sweden), performed analyses that estimated cost-effectiveness over the course of the 12-month trial and long-term. Costs were expressed in euros at 2010 prices and based on a Swedish setting. Ticagrelor was priced at €2.21 per day and generic clopidogrel at €0.06.

Ticagrelor Costs More—But Is Worth It

During the 12-month trial, the drug cost for patients receiving ticagrelor was €590 higher than that for patients receiving clopidogrel (P < 0.001). Overall, the mean per patient cumulative health-care cost—including expenses related to hospital stay, interventions, blood products, reoperations, and other factors—in the ticagrelor group was €96 higher than in the clopidogrel group, but the difference did not reach statistical significance (P = 0.679). In addition, mean estimated quality-adjusted life years (QALY; survival adjusted for disease burden) for the trial period were similar between the ticagrelor and clopidogrel groups at 0.846 and 0.840, respectively.

The long-term model was based on several possible clinical scenarios at the end of the PLATO study, estimating quality-adjusted survival and costs according to whether patients experienced MI, stroke, death, or neither of those events. For patients who did not experience stroke or MI, the ongoing annual risk of those events was estimated by extrapolating from the risk of clopidogrel-treated patients beyond 1 year. The annual mortality risk was based on age-specific rates from Swedish life tables.

Overall, the ticagrelor strategy was associated with a QALY gain of 0.1316 at an incremental cost of €362, yielding a cost per QALY gained of €2,753. The cost per life year gained was €2,372.

In sensitivity analyses, the results of the case-based scenarios were robust in the face of plausible variations in cost and QALY estimates. The highest cost per QALY, obtained by applying a ticagrelor price of €3, was €7,293.

In addition, the cost-effectiveness results were consistent across several subgroups, including patients with different forms of ACS (unstable angina, NSTEMI, or STEMI) and those with planned invasive management or diabetes. The highest cost per QALY with ticagrelor was for unstable angina at €6,400, and the lowest was for STEMI at €102.

Overall, treating ACS patients with ticagrelor compared with generic clopidogrel improved quality-adjusted survival at a cost well below generally accepted thresholds of cost-effectiveness.

Cost-Effectiveness Driven by Mortality Advantage

According to Deepak L. Bhatt, MD, MPH, of Brigham and Women's Hospital (Boston, MA), the key to the findings is that ticagrelor decreased all-cause mortality in the PLATO study. “When there’s a reduction in this hardest of all endpoints, in general cost-effectiveness follows,” he told TCTMD in a telephone interview. “So it’s not surprising that in ACS patients ticagrelor is cost-effective, but it’s nice to see it quantified at a level that most would deem highly cost-effective.”

David J. Cohen, MD, MSc, of Saint Luke’s Mid America Heart and Vascular Institute (Kansas City, MO), agreed. “Many people suspected the results would look something like this, and the authors’ methods seem quite solid,” he told TCTMD in a telephone interview.

But, he added, although the general conclusion regarding cost-effectiveness can probably be extrapolated to ACS care in the United States, “the specifics do not translate well.”

Lost in Translation?

The real question, Dr. Cohen continued, centers on the final costs, and how those translate “is a lot harder to say.” Though plugging the current US costs of clopidogrel and ticagrelor into the model is unlikely to change the overall conclusion, it would certainly change the numbers, he said, noting that ticagrelor is substantially less expensive in Sweden than in the United States.

On the other side of the equation, Dr. Bhatt observed that the very low price of generic clopidogrel used in the Swedish analysis reinforces the price differential between the drugs, making the finding of the cost-effectiveness of ticagrelor more robust. He added that although clopidogrel is now generic in the United States, the full effect of competition on the price has yet to be felt.

Dr. Bhatt also noted that a clinical argument could be made for performing a US-based analysis on the grounds of geographic heterogeneity in the PLATO results since ticagrelor did not reduce mortality in North American patients. If that finding cannot be explained by chance or differences in clinical practice, for example, the new drug would clearly not be cost-effective, he commented.

Dr. Cohen said he did not think the current analysis would carry much weight with US payers because it is designed for a European—and more specifically a Swedish—health-care audience. “I think you need to tailor the analysis directly to the payer you’re interested in,” he said. “I would be shocked if a US-specific analysis were not forthcoming.”

Related Stories:

• Ticagrelor More Effective Than Clopidogrel in ACS-With No Extra Bleeding
• Efficacy Data, Cost-Effectiveness Favor Ticagrelor and Prasugrel Over Clopidogrel in ACS
• Cost Effectiveness Results Favor Prasugrel Over Clopidogrel

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