Antiplatelet therapies for secondary stroke prevention: an update on clinical and cost-effectiveness.
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ABSTRACT:
SUBMITTER: Rothlisberger JM
PROVIDER: S-EPMC5549663 | biostudies-other | 2015 Aug
REPOSITORIES: biostudies-other
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Project description:Aspirin is recommended for patients with acute ischemic stroke within 24 hours of symptom onset. It may be beneficial for dual antiplatelet therapy including clopidogrel and aspirin to be administered in patients with minor stroke or transient ischemic attack for early secondary prevention, however, bleeding risk remains uncertain. This article will review the published literature concerning the role of dual antiplatelet therapy for secondary stroke prevention with focus on balancing both risk and benefit.
| S-EPMC6699814 | biostudies-literature
Project description:ObjectiveTo compare the cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in patients with atrial fibrillation (AF).MethodsUsing standard methods, we created a Markov decision model based on the estimated cost of apixaban and data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and other trials of warfarin therapy for AF. We quantified the cost and quality-adjusted life expectancy resulting from apixaban 5 mg twice daily compared with those from warfarin therapy targeted to an international normalized ratio of 2-3. Our base case population was a cohort of 70-year-old patients with no contraindication to anticoagulation and a history of stroke or TIA from nonvalvular AF.ResultsWarfarin therapy resulted in a quality-adjusted life expectancy of 3.91 years at a cost of $378,500. In comparison, treatment with apixaban led to a quality-adjusted life expectancy of 4.19 years at a cost of $381,700. Therefore, apixaban provided a gain of 0.28 quality-adjusted life-years (QALYs) at an additional cost of $3,200, resulting in an incremental cost-effectiveness ratio of $11,400 per QALY. Our findings were robust in univariate sensitivity analyses varying model inputs across plausible ranges. In Monte Carlo analysis, apixaban was cost-effective in 62% of simulations using a threshold of $50,000 per QALY and 81% of simulations using a threshold of $100,000 per QALY.ConclusionsApixaban appears to be cost-effective relative to warfarin for secondary stroke prevention in patients with AF, assuming that it is introduced at a price similar to that of dabigatran.
| S-EPMC3525294 | biostudies-literature
Project description:Clopidogrel's effectiveness is likely reduced significantly for prevention of thrombotic events after acute coronary syndrome (ACS) in patients exhibiting a decreased ability to metabolize clopidogrel into its active form. A genetic mutation responsible for this reduced effectiveness is detectable by genotyping. Ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. In 2011, clopidogrel will lose its patent protection and likely will be substantially less expensive than ticagrelor.To determine the cost-effectiveness of ticagrelor compared with a genotype-driven selection of antiplatelet agents.A hybrid decision tree/Markov model was used to estimate the 5-year medical costs (in 2009 US$) and outcomes for a cohort of ACS patients enrolled in Medicare receiving either genotype-driven or ticagrelor-only treatment. Outcomes included life years and quality-adjusted life years (QALYs) gained. Data comparing the clinical performance of ticagrelor and clopidogrel were derived from the Platelet Inhibition and Patient Outcomes trial.The incremental cost-effectiveness ratio (ICER) for universal ticagrelor was $10,059 per QALY compared to genotype-driven treatment, and was most sensitive to the price of ticagrelor and the hazard ratio for death for ticagrelor compared with clopidogrel. The ICER remained below $50,000 per QALY until a monthly ticagrelor price of $693 or a 0.93 hazard ratio for death for ticagrelor relative to clopidogrel. In probabilistic analyses, universal ticagrelor was below $50,000 per QALY in 97.7% of simulations.Prescribing ticagrelor universally increases quality-adjusted life years for ACS patients at a cost below a typically accepted threshold.
| S-EPMC3384486 | biostudies-literature
Project description:Our objective is to provide the reader with an overview as well as an update on current antiplatelet therapy for secondary stroke prevention. Relevant journals were hand-searched by the authors to compile a broad but by far not comprehensive summary of innovative and clinically relevant studies. Aspirin, clopidogrel and the combination of dipyridamole plus aspirin are the cornerstone therapy in secondary prevention after non-cardio-embolic stroke or transient ischaemic attack. A head-to-head comparison showed no difference in the prevention of recurrent stroke between dipyridamole plus aspirin and clopidogrel. More potent antiplatelet drugs or the combination of aspirin and clopidogrel prevent more ischaemic events, but also lead to more bleeding complications. For secondary stroke prevention in patients with atrial fibrillation, oral anticoagulation is more effective than aspirin or the combination of aspirin and clopidogrel.
| S-EPMC4373475 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Percutaneous transcatheter closure of patent foramen ovale (PFO closure) plus antiplatelet therapy has been shown to reduce the risk of recurrent stroke compared with medical therapy alone in carefully selected patients after cryptogenic stroke presumed to be from paradoxical embolism. Our objective was to determine the cost-effectiveness of PFO closure after cryptogenic stroke compared with conservative medical management from a US healthcare payer perspective. METHODS:A decision analytic Markov model estimated the 15-year cost and outcomes associated with the additional benefit of PFO closure compared with medical management alone. Model inputs were obtained from published literature, national databases, and a meta-analysis of 5 published randomized clinical trials on PFO closure. Health outcomes were measured in quality-adjusted life years (QALY). Cost-effectiveness used the incremental cost per QALY gained, whereas the net monetary benefit assumed a willingness to pay of $150?000/QALY. One-way and probabilistic sensitivity analyses estimated the uncertainty of model results. RESULTS:At 15 years, PFO closure compared with medical therapy alone improved QALY by 0.33 at a cost saving of $3568, representing an incremental net monetary benefit of $52?761 (95% interval -$8284 to $158?910). When the meta-analysis hazard ratio for stroke was increased to the 95% interval's upper bound of 0.77, one-way sensitivity analyses suggested that PFO closure's cost-effectiveness was $458?558 per additional QALY. Probabilistic sensitivity analysis suggested cost-effectiveness in 90% of simulation runs. CONCLUSIONS:PFO closure for cryptogenic strokes in the right setting is cost-effective, producing benefit in QALYs gained and potential cost savings. However, patient selection remains vitally important as marginal declines in treatment effectiveness can dramatically affect cost-effectiveness.
| S-EPMC5970986 | biostudies-literature
Project description:Antiplatelet agents are a cornerstone in the treatment of acute arterial thrombotic events and in the prevention of thrombus formation. However, existing antiplatelet agents (mainly aspirin, the combination of aspirin and dipyridamole and clopidogrel) reduce the risk of vascular events only by about one quarter compared with placebo. As a consequence, more efficacious antiplatelet therapies with a reduced bleeding risk are needed. We give an overview of several new antiplatelet agents that are currently investigated in secondary stroke prevention: adenosine 5'-diphosphonate receptor antagonists, cilostazol, sarpogrelate, terutroban and SCH 530348. There are unique features in secondary stroke prevention that have to be taken into account: ischaemic stroke is a heterogeneous disease caused by multiple aetiologies and the blood-brain barrier is disturbed after stroke which may result in a higher intracerebral bleeding risk. Several small randomized trials indicated that the combination of aspirin and clopidogrel might be superior to antiplatelet monotherapy in the acute and early post-ischaemic phase. There is an ongoing debate about antiplatelet resistance. Decreasing response to aspirin is correlated independently with an increased risk of cardiovascular events. However, there is still no evidence from randomized trials linking aspirin resistance and recurrent ischaemic events. Similarly, randomized trials have not demonstrated a clinical significantly decreased antiplatelet effect by the concomitant use of clopidogrel and proton pump inhibitors. Nevertheless, a routine use of this drug combination is not recommended.
| S-EPMC3823155 | biostudies-literature
Project description:Background The objective of the study was to assess the cost-effectiveness of cilostazol (a selective phosphodiesterase 3 inhibitor) added to aspirin or clopidogrel for secondary stroke prevention in patients with noncardioembolic stroke. Methods and Results A Markov model decision tree was used to examine lifetime costs and quality-adjusted life years (QALYs) of patients with noncardioembolic stroke treated with either aspirin or clopidogrel or with additional cilostazol 100 mg twice daily. Cohorts were followed until all patients died from competing risks or ischemic or hemorrhagic stroke. Probabilistic sensitivity analysis using Monte Carlo simulation was used to model 10 000 cohorts of 10 000 patients. The addition of cilostazol to aspirin or clopidogrel is strongly cost saving. In all 10 000 simulations, the cilostazol strategy resulted in lower health care costs compared with aspirin or clopidogrel alone (mean $13 488 cost savings per patient; SD, $8087) and resulted in higher QALYs (mean, 0.585 more QALYs per patient lifetime; SD, 0.290). This result remained robust across a variety of sensitivity analyses, varying cost inputs, and treatment effects. At a willingness-to-pay threshold of $50 000/QALY, average net monetary benefit from the addition of cilostazol was $42 743 per patient over their lifetime. Conclusions Based on the best available data, the addition of cilostazol to aspirin or clopidogrel for secondary prevention following noncardioembolic stroke results in significantly reduced health care costs and a gain in lifetime QALYs.
| S-EPMC9238703 | biostudies-literature
Project description:Stroke is one of the world's leading causes of disability and death. Antiplatelet agents are administered to acute ischemic stroke patients as secondary prevention. Clopidogrel involves biotransformation by cytochrome P450 (CYP) enzymes into an active metabolite, and single nucleotide polymorphisms (SNPs) can influence the efficacy of this biotransformation. Despite the therapeutic advantages of aspirin, there is significant inter-individual heterogeneity in response to this antiplatelet drug. In this clinical review, the recent advances in the biomarkers of antiplatelet agents in acute ischemic stroke are discussed. The studies reviewed herein highlight the clinical relevance of antiplatelet resistance, pharmacotherapy of antiplatelet agents predicting drug response, strategies for identifying aspirin resistance, pharmacogenetic variants of antiplatelet agents, miRNAs, and extracellular vesicles (EVs) as biomarkers toward the personalized approach in the management of acute ischemic stroke. The precise pathways contributing to antiplatelet resistance are not very well known but are presumably multi-factorial. It is essential to understand the clinical relevance of clopidogrel and aspirin-related single nucleotide polymorphism (SNPs) as potential predictive and prognostic biomarkers. Prasugrel is a next-generation antiplatelet agent that prevents ADP-platelet activation by binding irreversibly to P2Y12 receptor. There are sporadic reports of prasugrel resistance and polymorphisms in the Platelet endothelial aggregation receptor-1 (PEAR1) that may contribute to a change in the pharmacodynamics response. Ticagrelor, a direct-acting P2Y12-receptor antagonist, is easily absorbed and partly metabolized to major AR-C124910XX metabolite (ARC). Ticagrelor's primary active metabolite, ARC124910XX (ARC), is formed via the most abundant hepatic cytochrome P450 (CYP) enzyme, CYP3A4, and CYP3A5. The integration of specific biomarkers, genotype as well as phenotype-related data in antiplatelet therapy stratification in patients with acute ischemic stroke will be of great clinical significance and could be used as a guiding tool for more effective, personalized therapy.
| S-EPMC8222621 | biostudies-literature
Project description:Stroke is one of the leading causes of disability and death. Ischemic stroke is a syndrome with heterogeneous mechanisms and multiple etiologies, rather than a singularly defined disease. Approximately one third of ischemic strokes are preceded by another cerebrovascular ischemic event. Stroke survivors are at high risk of vascular events (i.e., cerebrovascular and cardiovascular events), particularly during the first several months after the ischemic event. The use of antiplatelet agents remains the fundamental component of secondary stroke prevention. Based on the available data, antiplatelet agents should be used for patients with noncardioembolic stroke. The use of combination therapy (aspirin plus clopidogrel) has not been proven to be effective or safe to use for prevention of early stroke recurrence or in long-term treatment. There is no convincing evidence that any of the available antiplatelet agents are superior for a given stroke subtype. Currently, the uses of aspirin, clopidogrel, or aspirin combined with extended release dipyridamole are all valid alternatives after an ischemic stroke or transient ischemic attack. However, to maximize the effects of these agents, the treatment should be initiated as early as possible and be continued on a lifelong basis.
| S-EPMC3250274 | biostudies-literature
Project description:Background and objectivesRivaroxaban is noninferior to warfarin for preventing stroke or systemic embolism in patients with high-risk atrial fibrillation (AF) and is associated with a lower rate of intracranial hemorrhage (ICH). We assessed the cost-effectiveness of rivaroxaban compared to adjusted-dose warfarin for the prevention of stroke in patients with nonvalvular AF.MethodsWe built a Markov model using the Korean Health Insurance Review & Assessment Service database. The base-case analysis assumed a cohort of patients with prevalent AF who were aged 18 years or older without contraindications to anticoagulation.ResultsNumber of patients with CHA?DS?-VASc scores 0, 1 and ?2 were 56 (0.2%), 1,944 (6.3%) and 28,650 (93.5%), respectively. In patients with CHA?DS?-VASc scores ?2, the incidence rate of ischemic stroke was 3.11% and 3.76% in warfarin and rivaroxaban groups, respectively. The incidence rates of ICH were 0.42% and 0.15%, and those of gastrointestinal bleeding were 0.32% and 0.15% in warfarin and rivaroxaban, respectively. Patients with AF treated with rivaroxaban lived an average of 11.8 quality-adjusted life years (QALYs) at a lifetime treatment cost of $20,886. Those receiving warfarin lived an average of 11.4 QALYs and incurred costs of $17,151. Patients with rivaroxaban gained an additional 0.4 QALYs over a lifetime with an additional cost of $3,735, resulting in an incremental cost-effectiveness ratio of $9,707 per QALY.ConclusionsPatients who had been treated with rivaroxaban may be a cost-effective alternative to warfarin for stroke prevention in Korean patients with AF.
| S-EPMC6393322 | biostudies-literature