Anticancer Activity and Mechanisms of Action of MAPK pathway inhibitors

We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a 50,000/quality-adjusted life-year threshold

We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a 50,000/quality-adjusted life-year threshold. Results Quality-adjusted life-years and costs of dual pathway inhibition were highest, the incremental cost-effectiveness ratios versus aspirin were 32,109 in coronary artery disease and 26,381 in peripheral arterial disease patients, with 92% and 56% cost-effectiveness probability, respectively (clopidogrel was extendedly dominated). for peripheral arterial disease, 75?mg clopidogrel. A comprehensive assessment of benefits, risks and costs of dual pathway inhibition versus standard of care is needed. Methods We used a state transition model including cardiovascular, ischaemic limb and bleeding events to compare dual pathway inhibition to aspirin antiplatelet therapy in coronary artery disease, and additionally to clopidogrel antiplatelet therapy in peripheral arterial disease patients. We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a 50,000/quality-adjusted life-year threshold. Results Quality-adjusted life-years and costs of dual pathway inhibition were highest, the incremental cost-effectiveness ratios versus aspirin were 32,109 in coronary artery disease and 26,381 in peripheral arterial disease patients, with 92% and 56% cost-effectiveness probability, respectively (clopidogrel was extendedly dominated). Incremental cost-effectiveness ratios were below 20,000 in comorbid peripheral Moxonidine Hydrochloride arterial disease patients and coronary artery disease patients younger than 65 years, incremental cost-effectiveness ratios were above 50,000 in carotid artery disease patients and coronary artery disease patients older than 75 years. Conclusion Lifelong preventive treatment of coronary artery disease and peripheral arterial disease patients at risk of cardiovascular events with dual pathway inhibition improves health outcomes and seems overall cost-effective relative to aspirin antiplatelet therapy and also to clopidogrel antiplatelet therapy for peripheral arterial disease, particularly in comorbid patients, but not in older patients and in carotid artery disease patients. These findings may warrant a targeted approach. strong class=”kwd-title” Keywords: Peripheral arterial disease, coronary artery disease, rivaroxaban, aspirin, clopidogrel, cost-benefit analysis Introduction Rivaroxaban is a selective oral factor Xa inhibitor that can be taken in combination with aspirin for cardiovascular risk reduction in patients with a history of cardiovascular disease.1 The COMPASS trial assessed the effectiveness of dual pathway inhibition (DPI) with rivaroxaban 2.5?mg twice daily plus 100?mg aspirin once daily (European Medicines Agency-recommended dose for atherosclerotic event prevention) compared with single antiplatelet therapy (ATP) with 100?mg aspirin in coronary artery disease (CAD) and peripheral arterial disease (PAD) patients.1,2 A cost-effectiveness analysis quantifying costs and health effects (quality of life (QoL) and survival) of DPI and relevant comparators, including clopidogrel 75?mg for PAD, is needed to support decision-making regarding the treatment of CAD and PAD patients with DPI. The main outcome of the COMPASS trial was major adverse cardiovascular events (MACE), the composite endpoint of non-fatal myocardial infarction (MI), ischaemic and haemorrhagic stroke (IS and HS) and cardiovascular death, and in PAD patients also, major adverse limb events (MALE), the composite endpoint of acute and chronic limb ischaemia and major vascular amputation. The trial showed a reduction of MACE and MALE with DPI versus aspirin ATP (CAD: hazard ratio (HR) MACE 0.74, 95% confidence interval (CI) 0.65C0.86;2 PAD: Moxonidine Hydrochloride HR MACE 0.72, 95% CI 0.57C0.90,1 HR MALE 0.54, 95% CI 0.35C0.82).1 However, the number of major bleedings was also higher (HR 1.66, 95% CI 1.37C2.03 in CAD,2 HR 1.61, 95% CI 1.12C2.31 in PAD).1 Risk reduction with anticoagulant and antiplatelet therapies are cornerstones in preventing cardiovascular and ischaemic limb events, which are responsible for the substantial morbidity and mortality associated with cardiovascular disease.3,4 New anticoagulant drugs such as rivaroxaban may reduce this disease burden. However, adding costly new drugs to the treatment regimen may put considerable health and financial burden on patients and society. Recently, health technology assessment bodies in England and The Netherlands recommended DPI for CAD and PAD treatment based on analyses provided by the manufacturer.5,6 A thorough assessment of health and financial effects by an independent party is needed. Based on results of the COMPASS trial and other literature, we estimated the cost-effectiveness of DPI with rivaroxaban plus aspirin versus aspirin ATP in CAD and PAD patients. Using a decision analytical model allowed us to consider a lifetime time horizon and to include clopidogrel ATP for PAD, which was not included in the COMPASS trial. The analysis reflects the costs and health consequences of cardiovascular events, limb events and bleeding events, and thereby addresses the trade-off between benefits and risks, and health outcomes.The ICER of DPI from a UK payer perspective was 23,605 in CAD patients and 40,889 in PAD patients (vs. dual pathway inhibition to aspirin antiplatelet therapy in coronary artery disease, and additionally to clopidogrel antiplatelet therapy in peripheral arterial disease patients. We calculated the incremental cost-effectiveness ratio from costs and quality-adjusted life-years of lifelong treatment, and the cost-effectiveness probability at a 50,000/quality-adjusted life-year threshold. Results Quality-adjusted life-years and costs of dual pathway inhibition were highest, the incremental cost-effectiveness ratios versus aspirin were 32,109 in coronary artery disease and 26,381 in peripheral arterial disease patients, with 92% and 56% cost-effectiveness probability, respectively (clopidogrel was extendedly dominated). Incremental cost-effectiveness ratios were below 20,000 in comorbid peripheral arterial disease patients and coronary artery disease patients younger than 65 years, incremental cost-effectiveness ratios were above 50,000 in carotid artery disease patients and coronary artery disease patients older than 75 years. Conclusion Lifelong preventive treatment of coronary artery disease and peripheral arterial disease patients at risk of cardiovascular events with dual pathway inhibition improves health outcomes and seems overall cost-effective relative to aspirin antiplatelet therapy and also to clopidogrel antiplatelet therapy for peripheral arterial disease, particularly in comorbid patients, but not in older patients and in carotid artery disease patients. These findings may warrant a targeted approach. strong class=”kwd-title” Keywords: Peripheral arterial disease, coronary artery disease, rivaroxaban, aspirin, clopidogrel, cost-benefit analysis Introduction Rivaroxaban is a selective oral factor Xa inhibitor that can be taken in combination with aspirin for cardiovascular risk reduction in patients with a history of cardiovascular disease.1 The COMPASS trial assessed the effectiveness of dual pathway inhibition (DPI) with rivaroxaban 2.5?mg twice SLC2A4 daily in addition 100?mg aspirin once daily (Western Medicines Agency-recommended dose for atherosclerotic event prevention) compared with solitary antiplatelet therapy (ATP) with 100?mg aspirin in coronary artery disease (CAD) and peripheral arterial disease (PAD) individuals.1,2 Moxonidine Hydrochloride A cost-effectiveness analysis quantifying costs and health effects (quality of life (QoL) and survival) of DPI and relevant comparators, including clopidogrel 75?mg for PAD, is needed to support decision-making regarding the treatment of CAD and PAD individuals with DPI. The main outcome of the COMPASS trial was major adverse cardiovascular events (MACE), the composite endpoint of non-fatal myocardial infarction (MI), ischaemic and haemorrhagic stroke (Is definitely and HS) and cardiovascular death, and in PAD individuals also, major adverse limb events (MALE), the composite endpoint of acute and chronic limb ischaemia and Moxonidine Hydrochloride major vascular amputation. The trial showed a reduction of MACE and MALE with DPI versus aspirin ATP (CAD: risk percentage (HR) MACE 0.74, 95% confidence interval (CI) 0.65C0.86;2 PAD: HR MACE 0.72, 95% CI 0.57C0.90,1 HR MALE 0.54, 95% CI 0.35C0.82).1 However, the number of major bleedings was also higher (HR 1.66, 95% CI 1.37C2.03 in CAD,2 HR 1.61, 95% CI 1.12C2.31 in PAD).1 Risk reduction with anticoagulant and antiplatelet therapies are cornerstones in preventing cardiovascular and ischaemic limb events, which are responsible for the considerable morbidity and mortality associated with cardiovascular disease.3,4 New anticoagulant medicines such as rivaroxaban may reduce this disease burden. However, adding expensive new medicines to the treatment regimen may put considerable health and monetary burden on individuals and society. Recently, health technology assessment bodies in England and The Netherlands recommended DPI for CAD and PAD treatment based on analyses provided by the manufacturer.5,6 A thorough assessment of health and financial effects by an independent party is needed. Based on results of the COMPASS trial and additional literature, we estimated the cost-effectiveness of DPI with rivaroxaban plus aspirin versus aspirin ATP in CAD and PAD individuals. Using a decision analytical model allowed us to consider a lifetime time horizon and to include clopidogrel ATP for PAD, which was not included in the COMPASS trial. The analysis reflects the costs and health effects of cardiovascular events, limb events.