Long-term Ticagrelor Therapy Cost-Effective in US Patients

From the perspective of the US healthcare system, 1 year of ticagrelor therapy is reasonably cost-effective compared with clopidogrel in patients with ACS, according to an economic analysis of the PLATO trial published February 2, 2015, in the Journal of the American College of Cardiology.

The multicenter PLATO (Platelet Inhibition and Patient Outcomes) trial, published in the New England Journal of Medicine in September 2009, randomized 18,624 ACS patients with or without STEMI to aspirin with either ticagrelor (Brilinta; AstraZeneca;180-mg loading dose followed by 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose followed by 75 mg daily thereafter). At 12 months, ticagrelor reduced the primary endpoint of cardiovascular death, MI, or stroke (9.8% vs 11.7%; P < .001), as well as all-cause death (4.5% vs 5.9%; P < .001), without increasing major bleeding (11.6% vs 11.2%; P = .43).Take Home: Long-term Ticagrelor Therapy Cost-Effective in US Patients

For the economic analysis, Patricia A. Cowper, PhD, of Duke University Medical Center (Durham, NC), and colleagues used patient-level clinical and resource use data from PLATO to assess both the cost and the cost-effectiveness of prescribing ticagrelor instead of clopidogrel in ACS patients from the perspective of US healthcare system thresholds. Consistent with the FDA approval for ticagrelor, it was assumed that the drug would be prescribed in the context of low-dose aspirin therapy.

Within Willingness-to-Pay Thresholds

Use of resources during the index hospitalization was similar in the ticagrelor and clopidogrel arms (mean length of stay 3.9 vs 4.1 days, respectively; P = .59), with approximately 70% of patients in each group undergoing PCI or CABG. Additionally, there were no differences in the mean number of readmissions.

Using a projection model, ticagrelor was predicted to improve life expectancy relative to clopidogrel by 1.92 months.

The additional cost of 1 year of ticagrelor therapy, relative to generic clopidogrel, was $29,665 per quality-adjusted life-year (QALY) gained, with a 98.7% likelihood of cost-effectiveness at a willingness-to-pay threshold of $100,000.

Cost-effectiveness improved slightly when the quality-of-life adjustment was removed ($25,457 per life-year gained) and when the annual cost of medical care after the trial was excluded ($16,050 per QALY gained). In sensitivity analyses, which included recalibrating survival projections to address concerns that the clinical effect achievable in the United States may be overestimated by the overall PLATO results, the incremental benefit fell from 0.14 to 0.10 QALYs, resulting in an incremental cost-effectiveness ratio (ICER) of $36,507 per QALY gained, with a 92% likelihood of cost-effectiveness.

Interestingly, ICERs varied across subgroups, with ticagrelor showing greater cost-effectiveness in those who underwent invasive procedures compared with those who received medical therapy ($27,331 vs $47,068 per QALY).

“Our analysis suggests that relative to the established [dual antiplatelet therapy] regimen of clopidogrel plus aspirin, ticagrelor plus low-dose aspirin increases life expectancy in ACS patients at an additional cost that compares favorably with accepted benchmarks for US medical interventions,” the study authors write.

However, they observe that “the financial impact on pharmacy budgets of widespread adoption of the new therapy at the current price could still be substantial,” and in the context of a “fragmented multipayer environment, those funding the medication may differ from those who recoup any potential cost offsets.”

Aspirin Dose, Price Differentials May Impact Results

In an accompanying editorial, Dhruv S. Kazi, MD, MSc, MS, of the University of California, San Francisco (San Francisco, CA), and Mark A. Hlatky, MD, of Stanford University School of Medicine (Stanford, CA), note that the PLATO results suggested that US patients had less benefit from ticagrelor than those in the rest of the world. One post hoc analysis theorizes that this may have been due to higher doses of aspirin given in the North American cohort.

Two factors in the new economic analysis deserve closer attention, according to Drs. Kazi and Hlatky.

“First, because incremental costs in this analysis were driven almost entirely by drug costs, the cost-effectiveness of ticagrelor varied substantially based on the price difference between ticagrelor and clopidogrel: the smaller the difference, the more economically attractive ticagrelor became,” they say. “Second, using outcomes from the entire study cohort might have overestimated the benefit of ticagrelor in the United States (as mortality in US patients was lower and absolute risk reductions drove the cost-effectiveness ratio).”

Trials Not Always Indicative of Real-World Use

Despite the study’s strengths, the editorialists caution that a number of limitations exist. “Incremental cost-effectiveness is always defined relative to an alternative, and the PLATO study examined only 1 of the many strategies for post-ACS antiplatelet use,” they write. Prasugrel was not considered as an alternative nor was personalized therapy with platelet testing or genotyping.

“Trial-based economic evaluations are necessarily tied to the design of the parent clinical trial and cannot address alternatives other than the randomized strategies,” Drs. Kazi and Hlatky add. “Also, the authors assumed that heterogeneity of treatment effectiveness for ticagrelor comparing the United States with the rest of the world was explained by the aspirin dose; they did not test the possibility of systematic variations in relative risk reduction from ticagrelor, which would have increased the uncertainty in the results beyond the bootstrap confidence intervals.”

Furthermore, they caution against assuming that the effectiveness of treatments in real-world practice will be the same as what is seen in randomized trials. In the case of ticagrelor, the twice-daily dosing—compared with just once a day for clopidogrel and prasugrel—along with higher risk of dyspnea may translate into patients not adhering to their drug regimen, the editorialists suggest.

“These cost-effectiveness estimates should be updated when real-world, postmarketing data for ticagrelor and prasugrel become available,” they conclude.

 


Sources:
1. Cowper PA, Pan W, Anstrom KJ, et al. Economic analysis of ticagrelor therapy from a U.S. perspective: results from the PLATO study. J Am Coll Cardiol. 2015;65:465-476.

2. Kazi DS, Hlatky MA. A delicate balance: the cost effectiveness of new antiplatelet agents [editorial]. J Am Coll Cardiol. 2015;65:477-479.

Disclosures:

  • This study was supported through a research grant from AstraZeneca. 
  • Dr. Cowper reports research support from AGA Medical, AstraZeneca, Bristol-Myers Squibb/Pfizer, and Eli Lilly.
  • Drs. Kazi and Hlatky report no relevant conflicts of interest.

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