Investigating the cost-effectiveness of antiplatelet medications in patients with type 2 diabetes for the secondary prevention of acute coronary syndromes

Gkountouras, Georgios (2020) Investigating the cost-effectiveness of antiplatelet medications in patients with type 2 diabetes for the secondary prevention of acute coronary syndromes. PhD thesis, University of Nottingham.

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Acute Coronary Syndrome (ACS) is a condition with very high clinical burden and financial burden worldwide and in the UK. ACS is more common in populations with Type 2 Diabetes Mellitus(T2DM), due to the vascular complications that people with T2DM face. This fact results in increased occurrence of ACS compared to the general population. ACS management is complex in T2DM populations because of the additional need for glycaemic control. Oral antiplatelet medication (clopidogrel, aspirin) is among the most important treatments for the secondary prevention of ACS.

New oral antiplatelet agents (ticagrelor, prasugrel) were compared as alternative treatments to clopidogrel in the general population. The new agents performed better than clopidogrel in terms of effectiveness and cost-effectiveness. The results of the effectivess of those agents in T2DM subgroups were available, but they were presented as an ad hoc analysis of the initial trials. This gap in research provided an opportunity for investigating effectiveness of antiplatelet medications in T2DM populations using real world data.

This study investigated the economic impact of different antiplatelet regimens in people with T2DM post-ACS, from the perspective of the NHS in England. The study aimed to gain an understanding of the characteristics of people with T2DM prescribed antiplatelet medications for secondary prevention post-ACS (demographics, clinical outcomes, medication usage, medication adherence, healthcare resource used, and costs), explain the variation in those clinical outcomes and costs, and investigate the effectiveness and cost-effectiveness of antiplatelet regimens in this population.

Using routinely collected data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES), a cohort study was carried out in order to investigate the effect of different antiplatelet regimens in patients with T2DM. Inverse probability treatment weights were obtained from propensity score models, and those weights were used to address the confounding that arised from the non-random assignment in antiplatelet regimens in the retrospectively observed data.

The time to event analysis found that the newer antiplatelet medications had better results than aspirin-clopidogrel for the outcomes investigated. The time to reccurence of a major adverse cardiovascular event (MACE) in patients treated with aspirin-prasugrel was approximately 4.4 times longer [Time Ratio (TR): 4.42; 95%CI: 1.73 to 11.28] compared to that of patients on aspirin-clopidogrel. No effect was found in patients who were prescribed aspirin-ticagrelor. Aspirin-prasugrel was associated with a 96% decrease in the hazard rate of stroke [Hazard Ratio (HR): 0.04 ;95% CI: 0.01 to 0.32] and aspirin-ticagrelor with a 78% decrease [Hazard Ratio (HR): 0.22 ;95% CI: 0.05 to 0.95] when compared with aspirin-clopidogrel.

The time to recurrence of a bleeding event in patients on aspirin-ticagrelor was approximately 12 times longer compared to that of patients on aspirin-clopidogrel [TR:11.89; 95%CI: 0.95 to 148.03]. No effect in bleeding was found in patients who were prescribed aspirin-prasugrel. Patients on aspirin-ticagrelor and aspirin-prasugrel survived 2.6 times [TR: 2.57;95% CI: 1.61 to 4.12] and 1.4 times longer [TR: 1.43;95% CI: 1.01 to 2.06] compared to patients treated with aspirin-clopidogrel. The findings are in partial accordance with the literature around the effectiveness of newer antiplatelet agents versus aspirin-clopidogrel.

The cost association analysis found that, on average, patients on aspirin-ticagrelor and aspirin-clopidogrel incur annually £6345 in total care health care costs. Patients on aspirin-prasugrel incurred 35% less costs (£4098).

The adherence analysis found that the average proportion of days covered (PDC) for all regimens is high and above the cut-off point of 80%. Patients on dual antiplatelet therapy regimens started discontinuing their therapies after 180 days. For the groups of aspirin- ticagrelor and aspirin-prasugrel there where no patients continuing their prescription after 450 days. In the aspirin-clopidogrel group the number of patients with prescriptions lasting more than 450 days was decreasing and the number of patients continuing with therapy for more than 450 days and less than 720 days was very small.

A decision analytical model was used to estimate the cost-effectiveness of alternative dual antiplatelet regimens and aspirin only. The analysis demonstrated that aspirin-ticagrelor generated more QALYs [0.67;95% CI:0.05 to 1.22] compared with aspirin only and costs [£1459.96; 95% CI: -5797.66 to 10056.77] over the lifetime horizon. Aspirin-prasugrel and aspirin-clopidogrel were extendedly dominated.

The probabilistic model estimated that aspirin-ticagrelor had the highest probability of being cost-effective for willingness to pay levels higher than £2000 per QALY. For a maximum willingness-to pay of £20000 per QALY the probability of cost-effectiveness was 90%. These findings were in accordance with similar studies for the general population.

This study allowed for a head-to-head comparison of alternative antiplatelet regimens for T2DM patients who suffered an ACS. Study findings were relevant for England only and not UK wide, because of the linkage of primary and secondary care data. The time-to-event and the cost analyses, even though they were carried out with the use of doubly robust estimation methods, potentially did not sufficiently address some of the confounding. In the Markov model, it was not possible to use a more complex treatment pattern in the patients who were assigned in DAPT regimen, and that could result in the potential overestimation cost-effectiveness.

Many T2DM patients were on monotherapy regimens for secondary prevention, even though this is not suggested in the clinical guidelines. Further investigation for this specific group is needed. T2DM patients who are on a DAPT regimen, tend to discontinue the treatment from the sixth month. This practice implication indicates the need for interventions that reduce DAPT discontinuation.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Elliott, Rachel
Avery, Anthony
Tanajewski, Lukasz
Keywords: Type 2 Diabetes, Markov modelling, adherence, antiplatelet, cost analysis, electronic health records, CPRD, time to event analysis, cost effectiveness
Subjects: R Medicine > RS Pharmacy and materia medica
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 61581
Depositing User: Gkountouras, Georgios
Date Deposited: 31 Dec 2020 04:40
Last Modified: 31 Dec 2020 04:40

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