PLATO economic analysis: Ticagrelor increased life expectancy at favorable additional cost

Treatment with ticagrelor plus aspirin was associated with extended life expectancy at an additional cost that was within accepted U.S. benchmarks for medical interventions, relative to treatment with clopidogrel plus aspirin, according to an economic analysis of the PLATO trial.

“Ticagrelor therapy for PLATO-eligible ACS patients, in combination with low-dose aspirin, is economically attractive relative to clopidogrel from the perspective of the U.S. health care system under a wide range of assumptions regarding health care costs and mortality benefit,” Patricia A. Cowper, PhD, from Duke Clinical Research Institute, Duke University Medical Center, and colleagues wrote.

The researchers analyzed patient-level clinical and resource use data from the PLATO trial to investigate the cost effectiveness and costs associated with ticagrelor (Brilinta, AstraZeneca) compared with clopidogrel in patients with ACS.

According to a lifetime extrapolation model, the undiscounted life expectancy of patients in the PLATO trial was 16.6 years in the ticagrelor group compared with 16.38 years in the clopidogrel group. After discounting at 3% per year, the average life expectancy with ticagrelor that exceeded that with clopidogrel by 0.16 years (P = .004). Quality of life, based on the EuroQol five-dimensional health state classification instrument, was 0.886.

Data on lifetime costs and cost effectiveness indicated that 1 year of treatment with ticagrelor cost $29,665 per quality-adjusted life-year gained compared with generic clopidogrel; 99% of bootstrap estimates were under the $100,000 willingness-to-pay threshold. The cost effectiveness of ticagrelor was improved when the researchers removed the QOL adjustment (incremental cost-effectiveness ratio = $25,457 per quality adjusted life year gained) and when they excluded the annual cost of medical care beyond the PLATO trial (incremental cost-effectiveness ratio = $16,050 per quality adjusted life year gained). The cost-effectiveness profile of ticagrelor was also better if the average cost of clopidogrel was raised to the proprietary cost of $6 per day (incremental cost-effectiveness ratio = $17,288); this finding was associated with 99% likelihood of meeting the $100,000 threshold, according to the results. If researchers limited the lifetime horizon to 5 years, the incremental cost-effectiveness ratio rose to $58,049 per quality adjusted life year gained and met the $100,000 threshold with “near certainty,” according to the results.

“Only in the most extreme scenario, which assumes that reductions in mortality observed in PLATO did not produce additional life expectancy beyond 1 year, was ticagrelor unlikely to be cost effective,” they wrote. In this case, the incremental cost-effectiveness ratio was $268,881 per quality adjusted life year gained.

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Extensive sensitivity analyses that included cost variations of clopidogrel, exclusion of costs in prolonged life years and survival estimates reflecting reduced mortality risk in the US population confirmed these results.

The researchers noted that the findings of this economic analysis “rest entirely on the mortality reduction observed in PLATO.”

Previously reported PLATO data demonstrated that ticagrelor plus aspirin was superior to clopidogrel plus aspirin for the prevention of vascular death, MI and stroke in patients with ACS (n = 18,624).

“Although our analyses showed ticagrelor to be a cost-effective treatment relative to clopidogrel in the US setting, the financial impact on pharmacy budgets of widespread adoption of the new therapy at the current price could still be substantial. Furthermore, in the current fragmented, multi-payer environment, those funding the medication may differ from those who recoup any potential cost offsets,” Cowper and colleagues wrote.

Mark A. Hlatky

Dhruv S. Kazi, MD, from the departments of medicine and epidemiology and biostatistics, University of California, San Francisco, and Mark A. Hlatky, MD, from the departments of health research and policy and medicine, Stanford University School of Medicine, discussed the findings in an accompanying editorial.

They noted that the data yielded “moderate variations” in the incremental cost-effectiveness ratio in certain clinical subgroups. For example, ticagrelor was more cost effective in patients who received invasive treatment ($27,300 per quality adjusted life year) compared with patients who received medical management ($47,000 per quality adjusted life year).

Kazi and Hlatky acknowledged that there are several limitations of this economic analysis, including the lack of consideration of alternative treatment options and no testing for the possibility of systematic variations in relative risk reduction from ticagrelor.

However, the wrote, with time, a better understanding of the effectiveness of ticagrelor in the real world, particularly compared with contemporary alternatives such as prasugrel or genotype-tailored strategies, will help identify the most cost-effective strategy for managing antiplatelet therapy after ACS.”

References:

Cowper PA, et al. J Am Coll Cardiol. 2015;doi:10.1016/j.jacc.2014.11.034.

Kazi DV, et al. J Am Coll Cardiol. 2015:doi:10.1016/j.jacc.2014.11.033.

Disclosure: The researchers report associations with companies including AGA Medical, AstraZeneca, Athera Biotechnologies, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Eli Lilly, Gilead, GlaxoSmithKline, Ikaria, Medtronic, Promedior, Regado Biosciences and Vertex. Kazi and Hlatky report no relevant financial disclosures.