Long-term Ticagrelor Post-MI of ‘Intermediate Value’: Cost-Effectiveness Study

There are significant costs to adding ticagrelor to low-dose aspirin, an economic analysis of PEGASUS-TIMI 54 shows.

Long-term Ticagrelor Post-MI of ‘Intermediate Value’: Cost-Effectiveness Study

Adding long-term 60-mg ticagrelor to low-dose aspirin in patients with prior MI is not necessarily a cost-effective treatment in most patients, according to a new economic analysis of the PEGASUS-TIMI 54 trial. Only in a subset of patients could the drug be considered a high-value therapy, researchers say.

Over a lifetime horizon, the addition of ticagrelor yielded an incremental cost-effectiveness ratio (ICER) of $94,917 per quality-adjusted life year (QALY) gained, falling outside of the current American College of Cardiology/American Heart Association guidelines range for “high value” of less than $50,000 for QALY gained.

“Cost-effectiveness analyses can yield information regarding patient subsets for whom an expensive therapy might be targeted to,” Elizabeth A Magnuson, ScD (Saint Luke’s Mid America Heart Institute, Kansas City, MO), told TCTMD. “In this case it was patients with peripheral artery disease or those less than 75 years old where ticagrelor would be considered a high-value treatment.”

The study appears early online today in the Journal of the American College of Cardiology.

Calculating Costs

The PEGASUS-TIMI 54 trial randomly assigned 21,162 patients to low-dose aspirin alone, ticagrelor 60 mg twice daily plus aspirin, or ticagrelor 90 mg twice daily plus aspirin. Treatment with both doses of ticagrelor reduced cardiovascular death, MI, or stroke compared with aspirin alone, but with an increased risk of major bleeding. The US Food and Drug Administration has since approved the 60-mg dose for long-term prevention of ischemic events in patients with a history of MI

Magnuson and colleagues performed a prospective economic substudy of the PEGASUS data by collecting medical resource data over a median of 33 months of follow-up and assessing costs based on the US healthcare system. By combining survival, utility, and cost data with lifetime projections, the researchers evaluated lifetime cost-effectiveness of the 60-mg dose of ticagrelor.

There was no significant difference in total hospitalization costs during the follow-up period for patients assigned ticagrelor compared with placebo (aspirin alone). Hospital costs were $2,262 per patient for ticagrelor and $2,333 for placebo. However, when the $10.52 cost of daily ticagrelor 60 mg was added, total costs were significantly greater for patients assigned to the drug ($10,016 vs $2,333; P < 0.001).

Cumulative QALYs during the trial period were similar between both study groups. Incorporating estimated long-term effects of nonfatal MI, stroke, and major bleeding events on projected survival, calculated over a lifetime horizon, assignment to ticagrelor was associated with a 0.078 QALY gain and incremental costs of $7,435, for a ICER of $94,917 per QALY gained.

Confirms ‘Bleeding Liability’

“Our analysis was the first cost-effectiveness analysis, I believe, related to this class of drugs that considered the long-term impact of nonfatal bleeding events,” Magnuson said. “When we removed that from the analysis, the cost-effectiveness ratio was reduced to around $70,000 per QALY.”

According to Eliano P. Navarese, MD, PhD (Inova Heart and Vascular Institute, Falls Church, VA), the incorporation of bleeding into this analysis, “confirms the importance of bleeding liability from both a clinical and economic perspective that was neglected in previous cost-effectiveness evaluations, which looked at ischemic risk reduction and associated costs only.”

Subgroup analyses revealed several categories of patients that might gain additional cost-effectiveness with ticagrelor. Patients with more than one prior MI, multivessel disease, diabetes, or renal dysfunction all had ICERs between $50,000 and $70,000 per QALY gained. Additionally, patients aged younger than 75 had an ICER of $44,779 per QALY gained and those with peripheral artery disease had an ICER of $13,427 for QALY gained.

“These findings highlight the importance of careful scrutiny of eligibility as applied to individual patients in routine practice,” said Navarese, who co-wrote an editorial published along with the study results. “Among the post-MI cohort investigated, only high ischemic risk groups had more favorable cost-efficacy profiles.”

According to Magnuson, data from cost-effectiveness studies are used to back up clinical practice guidelines and to help determine reimbursement policies and insurance coverage. Navarese added that the analysis confirms that one size does not fill all for most medications from a clinical and an economic standpoint.

“Antiplatelet therapy is associated with heterogeneity in benefit; a non-patient-centered strategy is intrinsically inefficient in terms of cost, safety, and outcomes,” Navarese said. “There is therefore an unmet need to fine-tune an individualized approach with the right medication to the right patient.”

The long-term use of ticagrelor after MI should be reserved for only those patients at the highest ischemic risk for whom it is cost-effective, Navarese said; however, this does not often happen in practice.

“Future non-industry-sponsored studies should be therefore directed to explore, one, the long-term use (beyond 1 year) after MI in overall and high ischemic risk patients of other antiplatelet medications as standard clopidogrel and compare them to ticagrelor from a cost-efficacy point of view, as well as, two, possible shortening of DAPT durations (less than 1 year) in high bleeding risk subjects,” Navarese said.

  • Magnuson EA, Li H, Wang K, et al. Cost-effectiveness of long-term ticagrelor in patients with prior myocardial infarction. Results from the PEGASUS-TIMI 54 Trial. J Am Coll Cardiol. 2017;70:572-586.

  • Navarese EP, Tijssen JGP. Striking the balance between benefits and costs of ticagrelor beyond 1 year after myocardial infarction. J Am Coll Cardiol. 2017:559-541.

  • Magnuson has received grant support from Abbott Vascular, AstraZeneca, Boston Scientific, Daiichi-Sankyo, Edwards Lifesciences, Merck, CSI, Eli Lilly, and Medtronic; and consulting fees from Daiichi-Sankyo.
  • Magnuson has received grant support from Abbott Vascular, AstraZeneca, Boston Scientific, Daiichi-Sankyo, Edwards Lifesciences, Merck, CSI, Eli Lilly, and Medtronic; and consulting fees from Daiichi-Sankyo.

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