Aspirin For Stroke Prevention Research Articles

Comprehensive systematic review and meta-analysis on anticoagulants and aspirin for stroke prevention in non-valvular atrial fibrillation patients.

Non-valvular atrial fibrillation (NVAF) is a common manifestation of cardiac arrhythmia, whose significance is heightened in the context of an aging global population and changing lifestyles, leading to an increased incidence. Stroke prevention in NVAF is a complex challenge that requires a comprehensive exploration of interventions. The emergence of Direct Oral Anticoagulants (DOACs) is a potential treatment, necessitating a thorough evaluation of their safety and efficacy. As the quest for the best strategy for thrombotic risk in these patients continues, the interaction between DOAC and aspirin has become the focus of research. With a rigorous methodological approach, we conducted a thorough search of scientific databases up to August 2023. The methodology involved meticulous screening, careful data extraction, and rigorous assessment of trial quality, all conducted by two independent investigators. The results were synthesized through standardized mean differences, accompanied by 95% confidence intervals. DOACs demonstrated significant enhancements in stroke prevention for NVAF, which was indicated by favorable outcomes in bleeding (RR = 4.04, 95% CI: 3.96, 4.12), coronary artery disease (RR = 2.45, 95% CI: 2.42, 2.48), mortality (RR = 0.49, 95% CI: 0.43, 0.56), myocardial infarction (RR = 1.85, 95% CI: 1.81, 1.88), and stroke (RR = 1.50, 95% CI: 1.47, 1.54). Notably, DOACs demonstrated optimal efficacy for NVAF patients with stroke. DOACs may be potentially effective for preventing stroke after NVAF.

Ticagrelor plus aspirin in patients with minor ischemic stroke and transient ischemic attack: a network meta-analysis

BackgroundDual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended as the secondary prevention of minor ischemic stroke or transient ischaemic attack (TIA). However, genetic polymorphisms of CYP2C19 had been identified as the major cause of poor responsiveness to clopidogrel. Ticagrelor, unlike clopidogrel, did not depend on metabolic activation, but it remained unclear whether ticagrelor was superior to clopidogrel in ischemic stroke. We performed a network meta-analysis to compare the efficacy and safety of ticagrelor, clopidogrel, and aspirin in the minor ischemic stroke and TIA populations.MethodsDatabases of Cochrane Library, ClinicalTrials.gov, and PubMed were searched up to June 19, 2023. Randomized controlled trials (RCTs) assessing antiplatelet drugs for minor stroke or TIA were included. Statistical processing was conducted by using multivariate meta-analysis routines of STATA.ResultsSeven RCTs were included involving 41,745 participants. There was no significant difference between the two DAPTs in preventing stroke recurrence (OR, 1.16; 95% CI, 0.93-1.44), ischemic stroke recurrence (OR, 1.16; 95% CI, 0.93-1.45), and major hemorrhage (OR, 1.22; 95% CI, 0.62,2.39). Compared with aspirin alone, the two DAPT regimen reduced the risk of stroke recurrence (clopidogrel: OR, 0.69; 95% CI, 0.60-0.80, ticagrelor: OR, 0.66; 95% CI, 0.49-0.87) and ischemic stroke recurrence, but increased the incidence of major hemorrhage (clopidogrel: OR, 2.05; 95% CI, 1.22- 3.77; ticagrelor: OR, 2.55; 95% CI, 1.25-4.99). Despite being associated with a higher risk of any bleeding, ticagrelor did not impact the composite of vascular events or mortality. While ticagrelor and aspirin reduced the risk of ischemic stroke recurrence (OR, 0.77; 95% CI, 0.63- 0.92) without increasing the risk of major bleeding (OR 0.94; 95% CI 0.45–1.95) in the Asian population mainly Chinese.ConclusionsDAPT was superior to aspirin in stroke prevention, but little difference existed between the two DAPT regimens. Asian population mainly Chinese may benefit from DAPT with aspirin and ticagrelor. But further head-to-head RCTs are needed to validate the study results.

Cost-effectiveness of apixaban versus other oral anticoagulants and aspirin for stroke prevention in atrial fibrillation in indian subcontinent

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Pfizer Ltd Background/Introduction Non-vitamin K antagonist oral anticoagulants (NOACs) are class I recommended by various guidelines for stroke prevention in atrial fibrillation. NOACs are associated with comparable or lower risk of stroke / systemic embolism and significantly lower major bleeding as compared to VKAs. Despite the fact that NOACs have demonstrated safety and efficacy in stroke prevention in AF by various randomized clinical trials and real-world evidences, the pharmacoeconomic data of NOACs in stroke prevention is lacking in India. In view of the higher initial and long-term cost of the NOAC therapy, it is important to analyze the cost effectiveness of such therapy to ensure wider acceptance and compliance to medication since majority of population in India is self-paying. Purpose The aim of this study was to evaluate the cost-effectiveness of apixaban versus other NOACs available in India (dabigatran and rivaroxaban), warfarin and aspirin for stroke prevention in atrial fibrillation from the healthcare providers’ and patients’ perspectives in the government healthcare as well as the private healthcare facilities across Indian subcontinent. Methods A Markov model was constructed using six-week cycle length over a lifetime horizon by including the available data from RCTs and real-world analyses of all NOACs. The clinical consequences of AF included in the analysis were stroke (ischemic and hemorrhagic), systemic embolism, bleeding (intracranial hemorrhage, other major and clinically relevant non-major), myocardial infarction, mortality and morbidity associated with NVAF not on anticoagulant. Innovator brands of NOACs were considered for this analysis, as NOACs are not under price control in India unlike warfarin and aspirin. Model outputs included quality-adjusted life years (QALY), life years gained, direct medical costs and incremental cost-effectiveness ratios (ICERs). Additional sensitivity and scenario analyses were conducted to test the robustness of the outcomes. Results From healthcare provider’s perspective irrespective of private medical facility or the government healthcare facilities, Apixaban was dominantly associated with cost-saving over other OACs. Apixaban was cost effective as compared to warfarin from patients’ perspective at the private medical facilities. Apixaban was cost-effective compared to dabigatran and rivaroxaban from patients’ perspective in the RWE-based analysis. Conclusion We conclude that apixaban is cost saving (less costly and more effective) compared to warfarin, aspirin and other NOACs from healthcare providers’ perspective. Apixaban may be a cost-effective alternative to dabigatran and rivaroxaban from patients’ perspective as per the RWD-based cost-effectiveness analysis. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare professionals and decision-makers. Abstract Figure. Incremental cost-effectiveness ratios

Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack.

In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points. In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%–2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%–0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%–1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. In patients with mild-moderate ischemic stroke or high-risk transient ischemic attack, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.

Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack in Prevention of Disabling Stroke

Reduction of subsequent disabling stroke is the main goal of preventive treatment in the acute setting after transient ischemic attack (TIA) or minor ischemic stroke. To evaluate the superiority of ticagrelor added to aspirin in preventing disabling stroke and to understand the factors associated with recurrent disabling stroke. The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) was a randomized clinical trial conducted between January 22, 2018, and December 13, 2019, with a 30-day follow-up, at 414 hospitals in 28 countries. The trial included 11 016 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk TIA, including 10 803 with modified Rankin Scale score (mRS) recorded at 30 days. Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo within 24 hours of symptom onset. All patients received aspirin, 300 to 325 mg on day 1 followed by 75 to 100 mg daily for days 2 to 30. Time to the occurrence of disabling stroke (progression of index event or new stroke) or death within 30 days, as measured by mRS at day 30. Disabling stroke was defined by mRS greater than 1. Among participants with 30-day mRS greater than 1, mean age was 68.1 years, 1098 were female (42.6%), and 2670 had an ischemic stroke (95.8%) as a qualifying event. Among 11 016 patients, a primary end point with mRS greater than 1 at 30 days occurred in 221 of 5511 patients (4.0%) randomized to ticagrelor and in 260 of 5478 patients (4.7%) randomized to placebo (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99, P = .04). A primary end point with mRS 0 or 1 at 30 days occurred in 70 of 5511 patients (1.3%) and 87 of 5478 patients (1.6%) (HR, 0.79; 95% CI, 0.57-1.08; P = .14). The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; 95% CI, 0.65-0.91; P = .002). Factors associated with disability were baseline National Institutes of Health Stroke Scale score 4 to 5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure, while treatment with ticagrelor was associated with less disability. In patients with TIA and minor ischemic stroke, ticagrelor added to aspirin was superior to aspirin alone in preventing disabling stroke or death at 30 days and reduced the total burden of disability owing to ischemic stroke recurrence. ClinicalTrials.gov Identifier: NCT03354429.

Abstract WMP112: Cilostazol versus Aspirin for Secondary Stroke Prevention: Systematic Review and Meta-Analysis

Introduction: Cilostazol has promise as an alternative to aspirin for secondary stroke prevention given its vasodilatory and anti-inflammatory properties in addition to platelet aggregation inhibition. We conducted a systematic review and meta-analysis to estimate the comparative effectiveness and safety of cilostazol compared to aspirin for stroke prevention in patients with previous stroke or TIA. Hypothesis: Cilostazol is more effective than aspirin in preventing recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials from inception to 2019. Randomized clinical trials that compared cilostazol vs aspirin and reported the endpoints of ischemic stroke, intracranial hemorrhage and bleeding were included. A random-effects estimate was computed based on Mantel-Haenszel methods. The pooled estimates with 95% confidence intervals were compared between cilostazol and aspirin and displayed as forest plots (Figure). Results: The search identified 5 randomized clinical trials comparing cilostazol vs aspirin for secondary stroke prevention that enrolled 7,240 patients from primarily Asian countries (3,615 received cilostazol and 3,625 received aspirin). The pooled results from the random-effects model showed that cilostazol was associated with significantly lower risk of recurrent ischemic stroke (Hazard ratio [HR] 0.70; 95%CI, 0.54-0.89), intracranial hemorrhage (HR 0.41; 95%CI, 0.25-0.65) and bleeding (HR 0.71; 95%CI, 0.55-0.91). See forest plots. Conclusion: This meta-analysis suggests cilostazol is more effective than aspirin in the prevention of recurrent ischemic stroke with lower risk of intracranial hemorrhage and bleeding. Confirmatory randomized trials of cilostazol for secondary stroke prevention to be performed in more generalizable populations are needed.

Correction to: Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors Japanese Primary Prevention Project.

Correction to: Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors Japanese Primary Prevention Project.

The management of childhood cancer survivors at risk for stroke: A Delphi survey of regional experts.

Evidence is not available to guide management of childhood cancer survivors (CCS) at risk for radiation-associated cerebral vascular disease (CVD) and stroke. We propose to use a consensus-based methodology to describe the collective opinion of regional experts for the care of these patients and identify areas of controversy. Thirty physicians from the New England region who care for CCS participated in a Delphi panel querying their management approach (imaging, laboratory tests, medications, counseling, referrals) to a CCS treated with cranial radiation formatted as five clinical scenarios (asymptomatic, small- and large-vessel CVD, transient ischemia, stroke) in three rounds of anonymous questionnaires. Consensus defined as≥90% agreement. Response rate was 100% for all three rounds. Panelists reached consensus on laboratory tests to assess stroke risk factors, stroke risk and prevention counseling, brain imaging to monitor survivors with known CVD, and acute care for stroke symptoms. Only 67% panelists agreed with MRI screening asymptomatic survivors with no history of CVD, 87% endorsed aspirin as stroke prevention for large-vessel CVD and 57% for small-vessel CVD. There was no consensus on specialty referrals. Overall, panelists practicing at large institutions and neurology subspecialists were more likely to advocate for screening, interventions, and referrals. Despite lack of evidence to guide stroke prevention in CCS treated with cranial radiation, a panel of regional physicians reached consensus on managing most clinical scenarios. Controversial areas requiring further study are surveillance imaging for asymptomatic survivors, aspirin for stroke prevention, and indications for specialty referral.

Aspirin for primary prevention of stroke in traumatic cerebrovascular injury: association with increased risk of transfusion.

Blunt traumatic extracranial carotid or vertebral artery injury (i.e., traumatic cerebrovascular injury [TCVI]) occurs in 1%-2% of all blunt trauma admissions, carries a 10% risk of thromboembolic ischemic stroke, and accounts for up to 9600 strokes annually in the US. Screening CT angiograms (CTAs) of patients with trauma has become ubiquitous in recent years, and patients with initially asymptomatic TCVI are commonly treated with antiplatelet agents to prevent stroke. Prophylaxis with antiplatelets is thought to be safer than anticoagulation, which carries a significant risk of hemorrhage in patients with trauma. However, the risk of hemorrhagic complications due to antiplatelets has not been assessed in this population. This is a retrospective cohort study of patients in whom a screening CTA was obtained after admission for blunt trauma at a Level 1 trauma center. Patients with CTAs indicating TCVI were treated routinely with 325 mg aspirin daily. The risk of transfusion > 24 hours after admission was compared according to CTA findings (CTA+ or CTA- for positive or negative findings, respectively) and aspirin treatment (ASA+ or ASA- for treatment or no treatment, respectively). The mean overall transfusion amount (number of units of packed red blood cells [PRBCs]) was 0.9 ± 2.1 for CTA+/ASA+ patients (n = 196) and 0.3 ± 1.60 for CTA-/ASA- patients (n = 2290) (p < 0.0001). In adjusted models, the overall relative risk (RR) of PRBC transfusion was 1.70 (1.32-2.20) for CTA+/ASA+ patients compared with CTA-/ASA- patients. Among age groups, participants whose ages were 50-69 years had the greatest significantly elevated RR (1.71, 95% CI 1.08-2.72) for CTA+/ASA+ patients compared with CTA-/ASA- patients. Treatment with aspirin for the prevention of stroke in patients with initially asymptomatic TCVI carries a significantly increased risk of PRBC transfusion. Future studies are needed to determine if this risk is offset by a reduced risk of ischemic stroke.

We have no real evidence related to anticoagulation plus aspirin for stroke prevention in atrial fibrillation

We have no real evidence related to anticoagulation plus aspirin for stroke prevention in atrial fibrillation

Cost Effectiveness of Apixaban versus Warfarin or Aspirin for Stroke Prevention in Patients with Atrial Fibrillation: A Greek Perspective

Strokes attributed to atrial fibrillation (AF) represent a major cause of adult disability and a great burden to society and healthcare systems. Our objective was to assess the cost effectiveness of apixaban, a direct acting oral anticoagulant (DOAC), versus warfarin or aspirin for patients with AF in the Greek healthcare setting. We used a previously published Markov model to simulate clinical events for patients with AF treated with apixaban, the vitamin K antagonist (VKA) warfarin, or aspirin. Clinical events (ischemic and hemorrhagic stroke, intracranial hemorrhage, other major bleed, clinically relevant non-major bleed, myocardial infarction, and cardiovascular [CV] hospitalizations) were modeled using efficacy data from the ARISTOTLE and AVERROES clinical trials. The cohort's baseline characteristics also sourced from these trials. Among VKA-suitable patients, 64.7% were men with a mean age of 70years and average CHADS2 (cardiac failure, hypertension, age, diabetes, stroke2) score of 2.1, whereas 58.5% of VKA-unsuitable patients were men with a mean age of 70years and a CHADS2 score of 2.0. A panel of experts (cardiologists and internists) provided information on the resource use associated with the management of AF. Cost calculations reflect the local clinical setting and a third-party payer perspective (€, discounted at 3%). Based on a simulation of 1000 VKA-suitable patients over a lifetime horizon, the use of apixaban versus warfarin resulted in 26 fewer strokes and systemic embolisms in total, 65 fewer bleeds, 41 fewer myocardial infarctions, and 29 fewer CV-related deaths, with an incremental cost-effectiveness ratio (ICER) of €14,478/quality-adjusted life-year (QALY). For VKA-unsuitable patients, apixaban versus aspirin resulted in 72 fewer strokes and systemic embolisms and 57 fewer CV-related deaths, with an ICER of €7104/QALY. Sensitivity analyses indicated that results were robust. Based on the present analysis, apixaban represents a cost-effective treatment option versus warfarin and aspirin for the prevention of stroke in patients with AF from a Greek healthcare payer perspective over a lifetime horizon.

Cost-effectiveness modelling of novel oral anticoagulants incorporating real-world elderly patients with atrial fibrillation

BackgroundNovel oral anticoagulants (NOACs) expand the treatment options for patients with atrial fibrillation (AF). Their benefits need to be weighed against the risk–benefit ratio in real-world elderly patients, prompting this cost-effectiveness study of NOACs (apixaban, dabigatran, edoxaban and rivaroxaban), warfarin and aspirin for stroke prevention in AF. MethodsApplying effectiveness estimates from a network meta-analysis involving over 800,000 patients from randomised controlled trials and observation studies, our Markov model projected cost and health outcomes for a cohort of 65-year-old AF patients over a life-time. We performed subgroup analysis stratified by age (65–74 and ≥75years), with further analysis limited to observational studies involving dabigatran and rivaroxaban. ResultsCompared to warfarin, NOACs (except dabigatran 110) were associated with incremental cost-effectiveness ratios ranging from USD 24,476 to USD 41,448 that were within cost-effectiveness threshold of USD 49,700 (one gross domestic product per capita in Singapore in 2015). Aspirin regimens were dominated. In elderly aged ≥75years, cost effectiveness of NOACs (except apixaban) decreased, owing to worsened performance in safety profile. Analysis limited to observational studies revealed that dabigatran 150 and rivaroxaban were not cost-effective, reflecting increased bleeding risks in non-controlled settings. Threshold analyses revealed that apixaban was no longer cost-effective at two to three times higher bleeding risk. ConclusionsWhilst NOACs are cost-effective in the younger elderly compared to warfarin, their benefits appear to be offset by worsened risk profile in older elderly, especially in non-controlled settings. Decisions on appropriate AF treatment should balance treatment-related benefits, risks, and patient preference.

Extended-release acetylsalicylic acid for secondary prevention of stroke and cardiovascular events

ABSTRACTIntroduction: Aspirin has been the bedrock of antiplatelet treatment strategies for the secondary prevention of recurrent cardiovascular and cerebrovascular events for the last 3 decades. The limitations of standard aspirin therapy include bleeding, gastrotoxicity, and loss of antiplatelet effect over a 24-hour period in selected high-risk patients. An extended-release (ER) aspirin formulation, Durlaza® (New Haven Pharmaceuticals, Inc., North Haven, CT), has been developed to address some of the latter limitations and may provide an alternative to standard aspirin in the secondary prevention of cardiovascular disease.Areas covered: We searched articles describing the use aspirin for secondary prevention of stroke and cardiovascular events in PubMed published until May 2016. This is a comprehensive review which describes active- and placebo-controlled clinical trials, overview of American and European recommendations, controversies surrounding standard aspirin use, and a description of pharmacodynamics of standard and extended release aspirin formulations.Expert commentary: Available data indicates an increased bleeding risk with the use of standard aspirin therapy in conjunction with potent P2Y12 receptor blockers, and/or oral anticoagulants. Trials evaluating the efficacy of replacing aspirin with a low-dose oral anticoagulant in patients with stable cardiovascular disease or acute coronary syndrome are ongoing. Future studies are warranted to determine if the use of ER-ASA formulation may obviate safety concerns surrounding standard aspirin therapy.

Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors: Japanese Primary Prevention Project.

The effect of aspirin in primary prevention of stroke is controversial among clinical trials conducted in Western countries, and no data are available for Asian populations with a high risk of intracranial hemorrhage. The objective of this study was to evaluate the effect of aspirin on the risk of stroke and intracranial hemorrhage in the Japanese Primary Prevention Project (JPPP). A total of 14 464 patients (age, 60-85 years) with hypertension, dyslipidemia, and diabetes mellitus participated and were randomized into 2 treatment groups: 100 mg of aspirin or no aspirin. The median follow-up period was 5.02 years. The cumulative rate of fatal or nonfatal stroke was similar for the aspirin (2.068%; 95% confidence interval [CI], 1.750-2.443) and no aspirin (2.299%; 95% CI, 1.963-2.692) groups at 5 years; the estimated hazard ratio was 0.927 (95% CI, 0.741-1.160; P=0.509). Aspirin nonsignificantly reduced the risk of ischemic stroke or transient ischemic attack (hazard ratio, 0.783; 95% CI, 0.606-1.012; P=0.061) and nonsignificantly increased the risk of intracranial hemorrhage (hazard ratio, 1.463; 95% CI; 0.956-2.237; P=0.078). A Cox regression adjusted by the risk factors for all stroke, which were age >70 years, smoking, and diabetes mellitus, supported the above result. Aspirin did not show any net benefit for the primary prevention of stroke in elderly Japanese patients with risk factors for stroke, whereas age >70 years, smoking, and diabetes mellitus were risk factors for stroke regardless of aspirin treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00225849.

Experts Say Abandon Aspirin for Stroke Prevention in AFib

Experts Say Abandon Aspirin for Stroke Prevention in AFib

Itchy erythroderma in a neoplastic patient—mind the mite!

A 75 year-old Caucasianman presentedwith an itchy erythrodermic dermatosis showing scaling in the arms and in the gluteal region (Fig. 1A, upper panel). Hewasundergoing amultidrug therapywith ciprofloxacin and salmeterol for a BPCO exacerbation, timolol for a glaucoma, citalopram and lormetazepam for anxious-depressive symptoms, and aspirin for stroke prevention. He had been surgically treated 4 years before for a prostatic adenocarcinoma (pT2c N0 at staging) and was recently diagnosed with a superficially invasive transitional carcinoma of the bladder. Due to the worsening erythroderma, he underwent a skin biopsy with a clinical suspect of erythrodermic psoriasis or adverse drug reaction. On histology, the skin showed only a mild perivascular inflammatory infiltrate of the dermis. The patient was then treated with methylprednisolone without any improvement. Therefore, a second histological examination was performed with three punch biopsies on the scaly sites. On histology, many mite parts and eggs were identified in the stratum corneum on a spongiotic epidermal background (Fig. 1B, lower panel). In the dermis, a mild perivascular inflammatory infiltrate was present.

Treatment Discontinuations With New Oral Agents for Long-term Anticoagulation: Insights From a Meta-analysis of 18 Randomized Trials Including 101,801 Patients

ObjectiveTo systematically examine discontinuation rates with new US Food and Drug Administration–approved oral anticoagulants (NOACs) in patients with various indications for long-term anticoagulation. Patients and MethodsPoor adherence to medications is considered a potential and frequent cause of treatment failure. We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases for articles published from January 1, 2001, through September 15, 2013. The following Medical Subject Heading terms and/or keywords were used for our database searches: rivaroxaban, dabigatran, apixaban, new oral anticoagulants, oral thrombin inhibitors, and oral factor Xa inhibitors. Articles in English that focused on randomized controlled trials (RCTs) comparing NOACs (apixaban, dabigatran, and rivaroxaban) with conventional therapy or placebo were abstracted. Independent extraction of relevant data was performed by 2 authors. The primary end point of interest was discontinuation due to all causes. Other end points of interest were discontinuation due to adverse events, consent withdrawal, and nonadherence. ResultsEighteen RCTs including a total of 101,801 patients were included for analysis. Total study drug discontinuation rates were not statistically different with NOACs in comparison to pharmacologically active comparators for treatment of venous thromboembolism/pulmonary embolism (risk ratio [RR], 0.91; 95% CI, 0.74-1.13; P=.40) and for NOACs in comparison to warfarin and aspirin for prevention of stroke in patients with atrial fibrillation (RR, 1.01; 95% CI, 0.87-1.17; P=.92). In contrast, in acute coronary syndromes, total study drug discontinuation with NOACs was significantly higher than with placebo (RR, 1.40; 95% CI, 1.07-1.83; P=.01). Overall discontinuations were comparable to those with active comparators. ConclusionStudy drug discontinuations with NOACs were not significantly different from those with conventional drugs in treatment of venous thromboembolism/pulmonary embolism and prevention of stroke in patients with atrial fibrillation but were worse in acute coronary syndromes as noted in evidence from contemporary RCTs.

Cost-effectiveness of Apixaban versus Warfarin and Aspirin in Sweden for Stroke Prevention in Patients with Atrial Fibrillation

IntroductionAtrial fibrillation (AF), one of the major risk factors for stroke, imposing a substantial burden to the Swedish health care system. Apixaban has demonstrated superiority to warfarin and aspirin in stroke prevention amongst patients with AF in two large randomised clinical trials. The aim of this study was to assess the economic implications of apixaban against warfarin and aspirin in these patients from a Swedish societal perspective. Materials and MethodsA Markov cohort model was constructed to characterise the consequences of anticoagulant treatment with regards to thromboembolic and bleeding events, as well as the associated health care costs, life-years and quality-adjusted life years (QALYs) for patients with AF treated with apixaban, warfarin or aspirin. Incremental cost-effectiveness ratios (ICERs) per QALY gained of apixaban relative to warfarin (among patients suitable for warfarin treatment) and aspirin (among patients unsuitable for warfarin treatment) were calculated. Costs (in 2011 SEKs) and QALYs were discounted at 3% per annum. ResultsThe model estimated the ICER of apixaban versus warfarin amongst patients who are suitable for warfarin therapy to be SEK 33,458/QALY gained and that of apixaban versus aspirin amongst those unsuitable for warfarin therapy to be SEK 41,453/QALY gained. Probabilistic sensitivity analyses indicate that apixaban is an optimal treatment option compared with warfarin and aspirin, when the willingness-to-pay is above SEK 35,000 and SEK 45,000 per QALY, respectively. ConclusionsApixaban was found to be a cost-effective alternative to warfarin and aspirin for stroke prevention in patients with AF in Sweden.

Intracranial Stenosis: Impact of Randomized Trials on Treatment Preferences of US Neurologists and Neurointerventionists

Background and Purpose: Medical and endovascular treatment options for stroke prevention in patients with symptomatic intracranial stenosis have evolved over the past several decades, but the impact of 2 major multicenter randomized stroke prevention trials on physician practices has not been studied. We sought to determine changes in US physician treatment choices for patients with intracranial atherosclerotic stenosis (ICAS) following 2 NIH-funded clinical trials that studied medical therapies (antithrombotic agents and risk factor control) and percutaneous transluminal angioplasty and stenting (PTAS). Methods: Anonymous surveys on treatment practices in patients with ICAS were sent to physicians at 3 time points: before publication of the NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial (pre-WASID survey, 2004), 1 year after WASID publication (post-WASID survey, 2006) and 1 year after the publication of the NIH-funded Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (post-SAMMPRIS survey, 2012). Neurologists were invited to participate in the pre-WASID survey (n = 525). Neurologists and neurointerventionists were invited to participate in the post-WASID (n = 598) and post-SAMMPRIS (n = 2,080) surveys. The 3 surveys were conducted using web-based survey tools delivered by E-mail, and a fax-based response form delivered by E-mail and conventional mail. Data were analyzed using the χ² test. Results: Before WASID, there was equipoise between warfarin and aspirin for stroke prevention in patients with ICAS. The number of respondents who recommended antiplatelet treatment for ICAS increased across all 3 surveys for both anterior circulation (pre-WASID = 44%, post-WASID = 85%, post-SAMMPRIS = 94%) and posterior circulation (pre-WASID = 36%, post-WASID = 74%, post-SAMMPRIS = 83%). The antiplatelet agent most commonly recommended after WASID was aspirin, but after SAMMPRIS it was the combination of aspirin and clopidogrel. The percentage of neurologists who recommended PTAS in >25% of ICAS patients increased slightly from pre-WASID (8%) to post-WASID surveys (12%), but then decreased again after SAMMPRIS (6%). The percentage of neurointerventionists who recommended PTAS in >25% of ICAS patients decreased from post-WASID (49%) to post-SAMMPRIS surveys (17%). Conclusions: The surveyed US physicians' recommended treatments for ICAS differed over the 3 survey periods, reflecting the results of the 2 NIH-funded clinical trials of ICAS and suggesting that these clinical trials changed practice in the USA.

Abstract T P338: To Evaluate the Efficacy and Safety of Cilostazol in Ischemic Stroke Patients with Peripheral Arterial Disease (SPAD) Study: Methodology and Baseline Data

Background and Purpose: Ischemic stroke often co-exists with peripheral arterial disease (PAD). Patients with polyvascular diseases carry higher risks of vascular events and death. We initiated a study to evaluate the safety and efficacy of cilostazol in ischemic Stroke patients with PAD (SPAD) and have been taking aspirin for stroke prevention. Methods: The SPAD study is a prospective, multicenter, national, double-blinded, placebo-controlled, randomized trial. Patients with previous ischemic stroke or TIA who have been taking aspirin (100 mg per day), aged 50 years or older, with PAD in the lower limbs based on ankle-brachial index (ABI) &lt;1.0 were randomized to the treatment group with cilostazol (200 mg/day) or the placebo group with a 1:1 basis. Each patient is periodically followed-up for one year. The primary endpoint of the study is the change in the ABI. The secondary endpoints are the change in the common carotid artery intima-media thickness (IMT); major cardiovascular events, including recurrent stroke, myocardial infarction, unstable angina, other vascular events, and all death; and the safety, including major bleeding events, hemorrhagic stroke, and any death. Results: From September, 2010 to July, 2012, a total of 800 patients (male, 59.9%; female, 40.1%; average age, 70.4±9.3 years) were enrolled in the SPAD study, including 722 (90.2%) with ischemic stroke or 78 (9.8%) with TIA. Several atherosclerotic risk factors were commonly seen in this study population, including hypertension (88%), diabetes mellitus (48%), hypercholesterolemia (54%), smoking habit (41%), and carotid stenosis (15%). The distribution of baseline ABI were 0.90-0.99 (n=294), 0.70-0.89 (n=371), and &lt;0.70 (n=136). Patients with lower ABI were more frequently associated with old age, lower body mass index, smoking habit, diabetes mellitus, carotid stenosis ≥50%, and higher systolic blood pressure. Conclusions: The SPAD trial is the first study to evaluate the safety and efficacy of dual antiplatelets, aspirin plus cilostazol, in ischemic stroke patients with PAD. The trial findings are expected to help in choosing better strategy for prevention of vascular events in this polyvascular disease.