Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes

Abstract Aim and hypotheses The THEMIS randomized trial compared ticagrelor plus aspirin versus placebo plus aspirin for patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), and without prior myocardial infarction (MI) or stroke. The aim of the study was to quantify the size of the CAD-T2DM population without prior MI or stroke population in a real-world setting, and more specifically populations with similar THEMIS selection criteria (THEMIS-like and THEMIS-PCI-like populations), as well as their risk of major outcomes in current practice. Methods A 2-year follow-up cohort study included all CAD-T2DM without MI/stroke prevalent patients on January 1st, 2014 in the SNDS French nationwide claims database. The THEMIS-like population concerned those ≥ 50 years of age with similar THEMIS inclusion and exclusion criteria. Prevalence was standardized to the European population. The cumulative incidence function was used to estimate the incidence of clinical outcomes (MI, ischemic stroke, and major bleeding according to the TIMI classification) with death as competing risk, and the Kaplan–Meier estimate for all-cause death and a composite outcome of MI, stroke and all-cause death. Results From a population of about 50 million adults, the prevalence of CAD-T2DM without MI/stroke, THEMIS-like and THEMIS-PCI-like populations was respectively at 6.04, 1.50 and 0.27 per 1000 adults, with a mean age of 72.7, 72.3 and 70.9 years and less comorbidities and diabetic complications for the THEMIS-like and THEMIS-PCI-like population. The 2-year cumulative incidence was respectively 1.7%, 1.3% and 1.6% for MI, 1.7%, 1.5% and 1.4% for stroke, 4.8%, 3.1% and 2.9% for major bleeding, 13.6%, 9.7% and 6.8% for all-cause death, and 16.2%, 12.0% and 9.5% for the composite outcome. Conclusion THEMIS-like prevalence was estimated at 1.50 per 1,000 adults, representing about a quarter of CAD-T2DM without MI/stroke patients, and 0.27 per 1000 adults for the THEMIS-PCI-like populations. In current French practice, the median age of both these populations was about 5–6 years older than in the THEMIS trial, with a 2-year incidence of major outcomes between two or four time above the ones of the placebo arm of the THEMIS trial using very close definitions. Registration No. EUPAS27402 (http://www.ENCEPP.eu).

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Cost-effectiveness of ticagrelor in patients with type 2 diabetes and coronary artery disease with a history of PCI: an economic evaluation of THEMIS-PCI using a Swedish healthcare perpective

European Heart Journal ◽

10.1093/ehjci/ehaa946.3538 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Steg ◽

D.L Bhatt ◽

S.K James ◽

O Darlington ◽

L Hoskin ◽

...

Keyword(s):

Myocardial Infarction ◽

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Cost Effectiveness ◽

Coronary Artery ◽

Cost Effective ◽

Funding Source ◽

History Of ◽

Artery Disease

Abstract Background The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) evaluated ticagrelor compared to placebo for the prevention of myocardial infarction (MI), stroke and cardiovascular (CV) death in 19 220 patients with type 2 diabetes (T2DM) and stable coronary artery disease (CAD) with no prior myocardial infarction (MI) or stroke. THEMIS-PCI was a pre-specified subgroup of 11 154 patients who had a history of percutaneous coronary intervention (PCI) when entering the study. In THEMIS, ticagrelor reduced CV death, MI or stroke, although with an increase in major bleeding compared to aspirin alone, and there was a significant interaction between a prior history of PCI and the net benefit of ticagrelor. In the THEMIS-PCI population, ticagrelor plus aspirin provided a favourable net clinical benefit with a significant 15% reduction in all-cause death, MI, stroke, fatal bleed, or intracranial haemorrhage. Objective The objective of this analysis was to estimate the cost-effectiveness of ticagrelor for the prevention of CV events based on the results of the THEMIS-PCI population using a lifetime horizon from a Swedish healthcare perspective. Methods A lifetime Markov state transition model was developed with health states aligned to the THEMIS trial endpoints. Health state transitions were informed by parametric survival equations fitted to patient level data from THEMIS-PCI population. Treatment discontinuation rates were informed by the THEMIS-PCI population, with all patients assumed to discontinue treatment with ticagrelor after four years. The incidence of bleeding and dyspnoea were modelled as adverse events. Costs (2019 Euros) and utility data were derived from the published literature and the THEMIS-PCI population, respectively, and discounted at 3.0% annually. Probabilistic (PSA) and deterministic sensitivity analysis (DSA) were conducted to quantify uncertainty of key input parameters. Results Treatment with ticagrelor plus aspirin over four years resulted in estimated Quality Adjusted Life Year (QALY) gains of 0.09 at an incremental cost of €1,891 compared to aspirin alone. The estimated incremental cost-effectiveness ratio (ICER) was €19,959/QALY. PSA indicated that ticagrelor was cost-effective in 93% of simulations using a willingness-to-pay threshold of €47,000/QALY and DSA showed that cost-effectiveness was robust to changes in key input parameters (ICER range: €16,504 to €25,012/QALY). Conclusion Based on the results of the THEMIS trial, dual antiplatelet therapy with ticagrelor plus aspirin is likely to be a cost-effective treatment compared with aspirin alone for the prevention of CV events in patients with T2DM and CAD with a history of PCI. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

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