201 research outputs found
Clinical update on the therapeutic use of clopidogrel: treatment of acute ST-segment elevation myocardial infarction (STEMI)
The pathogenesis of ST-elevation myocardial infarction (STEMI) involves plaque disruption, platelet aggregation and intracoronary artery thrombus formation. Aspirin is the cornerstone of antiplatelet therapy in patients with STEMI, reducing the risk of recurrent myocardial infarction or death during the acute phase and long term by about one-quarter. Recent large randomized trials have demonstrated that the addition of clopidogrel to aspirin reduces the risk of major ischemic events by up to a further one-third in patients with STEMI treated with fibrinolytic therapy and undergoing percutaneous coronary intervention, with no significant increase in bleeding. Thus, dual antiplatelet therapy with the combination of clopidogrel and aspirin is becoming the new standard of care for the management of patients with STEMI
Implications of the antiplatelet therapy gap left with discontinuation of prasugrel in Canada
Background
The current Canadian Cardiovascular Society antiplatelet therapy guidelines recommend the use of ticagrelor or prasugrel over clopidogrel as first-line platelet P2Y12 receptor antagonists for treatment of moderate- to high-risk acute coronary syndromes. Recently, Effient (prasugrel [Eli Lilly Canada Inc, Toronto, Canada]) was discontinued by its distributor in Canada.
Methods
Five members of the Canadian Cardiovascular Society antiplatelet therapy 2018 guidelines committee undertook an independent, evidence-based review to outline patients for whom prasugrel should be the optimal P2Y12 agent and discuss alternative strategies to consider without prasugrel.
Results
Several clinical scenarios where prasugrel should be indicated are identified and discussed. Considerations to be undertaken for alternative therapies are summarized, including a review of national and international guidelines for de-escalation of P2Y12 receptor antagonists.
Conclusions
The discontinuation of prasugrel poses a challenge for clinicians. Clinicians must consider key factors in determining the best alternate therapy.Introduction
Dans ses lignes directrices actuelles sur la thĂ©rapie antiplaquettaire, la SociĂ©tĂ© canadienne de cardiologie recommande lâutilisation du ticagrĂ©lor ou du prasugrel plutĂŽt que lâutilisation du clopidogrel comme antagonistes des rĂ©cepteurs plaquettaires P2Y12 de premiĂšre intention dans le traitement des patients qui prĂ©sentent un risque modĂ©rĂ© Ă Ă©levĂ© de syndromes coronariens aigus. Depuis peu, le distributeur a cessĂ© la distribution dâEffient (prasugrel) au Canada.
MĂ©thodes
Cinq membres du comitĂ© des lignes directrices 2018 sur la thĂ©rapie antiplaquettaire de la SociĂ©tĂ© canadienne de cardiologie ont entrepris une revue indĂ©pendante fondĂ©e sur les donnĂ©es probantes pour dresser le profil des patients pour lesquels le prasugrel devrait ĂȘtre la meilleure option parmi les antagonistes des rĂ©cepteurs P2Y12 et se pencher sur les traitements alternatifs en l'absence de prasugrel.
RĂ©sultats
Plusieurs scĂ©narios cliniques oĂč le prasugrel devrait ĂȘtre indiquĂ© sont recensĂ©s et abordĂ©s. Les rĂ©flexions sur les solutions de rechange au traitement, notamment une revue des lignes directrices nationales et internationales en matiĂšre de dĂ©sescalade des antagonistes des rĂ©cepteurs P2Y12, sont prĂ©sentĂ©es.
Conclusions
La cessation de la distribution du prasugrel pose problÚme aux cliniciens. Les cliniciens doivent tenir compte des facteurs clés pour déterminer le meilleur traitement de remplacement
Double-Dose Versus Standard-Dose Clopidogrel According to Smoking Status Among Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention
Background: Prior Studies have suggested better outcomes in smokers compared with nonsmokers receiving clopidogrel (âsmoker's paradoxâ). The impact of a more intensive clopidogrel regimen on ischemic and bleeding risks in smokers with acute coronary syndromes requiring percutaneous coronary interventions remains unclear. Methods and Results: We analyzed 17 263 acute coronary syndrome patients undergoing percutaneous coronary intervention from the CURRENTâOASIS 7 (Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent EventsâSeventh Organization to Assess Strategies in Ischemic Symptoms) trial, which compared doubleâdose (600 mg day 1;150 mg days 2â7; then 75 mg daily) versus standardâdose (300 mg day 1; then 75 mg daily) clopidogrel in acute coronary syndrome patients. The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days. Interactions between treatment allocation and smoking status (current smokers versus nonsmokers) were evaluated. Overall, 6394 patients (37.0%) were current smokers. For the comparison of doubleâ versus standardâdose clopidogrel, there were significant interactions in smokers and nonsmokers for the primary outcome (P=0.031) and major bleeding (P=0.002). Doubleâ versus standardâdose clopidogrel reduced the primary outcome among smokers by 34% (hazard ratio [HR] 0.66, 95% confidence interval [CI], 0.50â0.87, P=0.003), whereas in nonsmokers, there was no apparent benefit (HR 0.96, 95% CI, 0.80â1.14, P=0.61). For major bleeding, there was no difference between the groups in smokers (HR 0.77, 95% CI, 0.48â1.24, P=0.28), whereas in nonsmokers, the doubleâdose clopidogrel regimen increased bleeding (HR 1.89, 95% CI, 1.37â2.60, P<0.0001). Doubleâdose clopidogrel reduced the incidence of definite stent thrombosis in smokers (HR 0.41, 95% CI, 0.24â0.71) and nonsmokers (HR 0.63, 95% CI, 0.42â0.93; P for interaction=0.19). Conclusions: In smokers, a doubleâdose clopidogrel regimen reduced major cardiovascular events and stent thrombosis after percutaneous coronary intervention, with no increase in major bleeding. This suggests that clopidogrel dosing in patients with acute coronary syndromes should be personalized, taking into consideration both ischemic and bleeding risk. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00335452
Cost-effectiveness of ticagrelor in patients with type 2 diabetes and coronary artery disease: a European economic evaluation of the THEMIS trial.
To conduct a health economic evaluation of ticagrelor in patients with type 2 diabetes and coronary artery disease (CAD) from a multinational payer perspective. Cost-effectiveness and cost-utility of ticagrelor were evaluated in the overall effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS) trial population and in the predefined patient group with prior percutaneous coronary intervention.
A Markov model was developed to extrapolate patient outcomes over a lifetime horizon. The primary outcome was incremental cost-effectiveness ratios (ICERs), which were compared with conventional willingness-to-pay thresholds [âŹ47 000/quality-adjusted life-year (QALY) in Sweden and âŹ30 000/QALY in other countries].Treatment with ticagrelor resulted in QALY gains of up to 0.045 in the overall population and 0.099 in patients with percutaneous coronary intervention (PCI). Increased costs and benefits translated to ICERs ranged between âŹ27 894 and âŹ42 252/QALY across Sweden, Germany, Italy, and Spain in the overall population. In patients with prior PCI, estimated ICERs improved to âŹ18 449, âŹ20 632, âŹ20 233, and âŹ13 228/QALY in Sweden, Germany, Italy, and Spain, respectively, driven by higher event rates and treatment benefit.
Based on THEMIS results, ticagrelor plus aspirin compared with aspirin alone may be cost-effective in some European countries in patients with T2DM and CAD and no prior myocardial infarction (MI) or stroke. Additionally, ticagrelor is likely to be cost-effective across European countries in patients with a history of PCI.This work was supported by AstraZeneca.S
External applicability of the Effect of ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) trial: An analysis of patients with diabetes and coronary artery disease in the REduction of Atherothrombosis for Continued Health (REACH) registry.
THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry.
The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients â„50Â years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of â„50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy.
In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.'
http://www.
gov identifier: NCT01991795.The THEMIS trial was funded by AstraZeneca. The REACH registry
was sponsored by Sanofi, Bristol-Myers Squibb, and the Waksman
Foundation (Tokyo, Japan) and is endorsed by the World Heart
Federation.S
Probabilistic analysis of the phase space flow for linear programming
The phase space flow of a dynamical system leading to the solution of Linear
Programming (LP) problems is explored as an example of complexity analysis in
an analog computation framework. An ensemble of LP problems with variables
and constraints (), where all elements of the vectors and matrices are
normally distributed is studied. The convergence time of a flow to the fixed
point representing the optimal solution is computed. The cumulative
distribution of the convergence rate
to this point is calculated analytically, in the asymptotic limit of large
, in the framework of Random Matrix Theory. In this limit is found to be a scaling function, namely it is a function
of one variable that is a combination of , and rather then a
function of these three variables separately. From numerical simulations also
the distribution of the computation times is calculated and found to be a
scaling function as well.Comment: 8 pages, latex, 2 eps figures; final published versio
Psychological Ownership: Theoretical Extensions, Measurement, and Relation to Work Outcomes
Viewing psychological ownership as a positive resource for impacting human performance in organizations, the present study investigated the components of an expanded view of psychological ownership. Confirmatory factor analyses on a proposed measure of psychological ownership provided support for a positively-oriented, ââpromotion-focusedââ aspect of psychological ownership comprised of four dimensions: self-efficacy, accountability, sense of belongingness, and self-identity. In addition, territoriality was examined as a unique and more ââprevention-focusedââ form of ownership. Practical implications and suggestions for future research on psychological ownership and positive organizational behavior conclude the article
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