Absolute Risk Reduction Of Stroke Research Articles

Number needed to treat for net effect of anticoagulation in atrial fibrillation: Real-world vs. clinical-trial evidence.

The net benefit of oral anticoagulants (OACs) in atrial fibrillation (AF) is poorly understood. We aimed to determine the NNT for net effect (NNTnet ) using calculator of absolute stroke risk (CARS) in anticoagulated patients with AF in real-world and clinical trial cohorts. Post-hoc analysis of patient-level data from the real-world Murcia AF Project and AMADEUS clinical trial. Baseline risk of stroke was determined using CARS. The risk of stroke and major bleeding events with OAC were determined using the number of respective events at 1-year. NNTnet was calculated as a reciprocal of the net effect of absolute risk reduction with OAC (NNTnet =1/(absolute risk reduction of stroke[ARRstroke ] - absolute risk increase of major bleeding[ARIbleeding ])). In total, 3511 patients were included (1306 [37.2%] real-world patients and 2205 [62.8%] clinical trial participants). The absolute 1-year stroke risk was similar across both cohorts. In the real-world cohort, OAC was associated with a 4.0% ARRstroke , 25 NNTbenefit , 1.0% ARIbleeding , 100 NNTharm and 34 NNTnet . In the clinical trial cohort, OAC was associated with a 3.8% ARRstroke , 27 NNTbenefit , 1.6% ARIbleeding , 63 NNTharm and 46 NNTnet . In both cohorts, the NNTnet was significantly lower in patients with an excess stroke risk of ≥2% by CARS. Overall, the NNTnet approach in AF incorporates information regarding baseline risk of stroke and major bleeding, and relative effects of OAC with the potential to include multiple additional outcomes and weighting of events based on their perceived effects by individual patients.

Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin.

Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo added to aspirin (300-325 mg on day 1 followed by 75-100 mg daily for days 2-30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56-0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19-171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74-1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04-16.9], P=0.001). In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19-171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta-Analysis, and New Insights From the CLOSE Study.

BackgroundWe conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with PFO‐associated cryptogenic stroke.Methods and ResultsWe searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random‐effects meta‐analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17–0.79; I2=59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11–0.70; I2=42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43–1.47; I2=12%). Major complications occurred in 2.40% (95% CI, 1.03–4.25; I2=77%) of procedures. New‐onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37–7.89; I2=14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00–1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05–0.63; I2=12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference.Conclusions PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle‐aged patients. PFO closure was associated with an increased risk of atrial fibrillation.

Clinical Effect and Cost-Effectiveness of Screening for Asymptomatic Carotid Stenosis: A Markov Model

The cost-effectiveness of screening depends on the cost of screening, prevalence of asymptomatic carotid artery stenosis (ACAS), and the potential effect of medical intervention in reducing the risk of stroke. The aim of the study was to determine the threshold values for these parameters in order for screening for ACAS to be cost-effective. The clinical effect and cost-effectiveness of ultrasound screening for ACAS with subsequent initiation of preventive therapy versus not screening was assessed in a Markov model with a lifetime perspective. Key parameters, including stroke risk, all cause mortality, and costs, were based on contemporary published data, population statistics, and data from an ongoing screening program in Uppsala county (population 300,000), Sweden. Prevalence of ACAS (2%) and the rate of best medical treatment (BMT; 40%) were based on data from a male Swedish population recently screened for ACAS. The required stroke risk reduction from BMT, incremental cost-efficiency ratio (ICER), absolute risk reduction for stroke (ARR), and number needed to screen (NNS) were calculated. Screening was cost-effective at an ICER of €5744 per incremental quality adjusted life year (QALY) gained. ARR was 135 per 100,000 screened, NNS was 741, and QALYs gained were 6700 per 100,000 invited. At a willingness to pay (WTP) threshold of €50,000 per QALY the minimum required stroke risk reduction from BMT was 22%. The assumed degree of stroke risk reduction was the most important determinant of cost-efficiency. A moderate (22%) reduction in the risk of stroke was required for an ACAS screening strategy to be cost-effective at a WTP of €50,000/QALY. Targeting populations with a higher prevalence of ACAS could further improve cost-efficiency.

Coronary surgery is superior to drug eluting stents in multivessel disease. Systematic review and meta-analysis of contemporary randomized controlled trials

ObjectiveCurrent randomized controlled trials (RCTs) comparing percutaneous coronary intervention with drug eluting stent (DES-PCI) with coronary artery bypass grafting (CABG) in multivessel disease are underpowered to detect a difference in hard clinical end-points such as mortality, myocardial infarction and stroke. We aimed to overcome this limitation by conducting a meta-analysis of contemporary RCTs. MethodsA systematic literature search was conducted for all RCTs comparing DES-PCI versus CABG in multivessel disease published through May 2015. Inverse variance weighting was used to pool data from individual studies (<1 favouring DES-PCI and >1 CABG favouring surgery). ResultsA total of five randomized trials including 4563 subjects were analysed. After an average follow-up of 3.4years, DES-PCI was associated with a significantly increased risk of overall mortality (HR 1.51; 95%CI 1.23–1.84; P<0.001), MI (HR 2.02; 95%CI 1.57–2.58; P<0.001) and repeat revascularization (HR 2.54; 95%CI 2.07–3.11; P=<0.001). CABG marginally increased the risk of stroke (HR 0.70; 95%CI 0.50–0.98; P=0.04). The absolute risk reduction for all-cause mortality (3.3%) and myocardial infarction (4.3%) with CABG was larger than the absolute risk reduction for stroke (0.9%) with DES-PCI. ConclusionIn patients with multivessel coronary disease, CABG was found to be superior to DES-PCI by reducing the risk of mortality and subsequent myocardial infarction at the expense of a marginally increased risk of stroke.

A decisional model to individualize warfarin recommendations: Expected impact on treatment and outcome rates in a real-world population with atrial fibrillation

BackgroundHow the adoption of prediction models to decide which patient with atrial fibrillation (AF) to anticoagulate can affect prescription rates and outcomes is unclear. MethodsWe retrospectively analyzed data from Danish registries on patients with a first-time recorded AF from 2005 to 2010. We simulated the adoption of a decisional model based on the individual absolute risk reduction of stroke and absolute risk increase of bleeding with warfarin, as expected from the patient CHA2DS2-VASc and HAS-BLED, adjusted for a 0.6 relative value for bleeding versus stroke. We studied 3 different model versions and calculated for each of them the net benefit associated with its adoption, measured as the value-adjusted reduction in stroke and bleeding events at 1year, compared with i) the actual practice, or ii) recommending warfarin consistently with the European Society of Cardiology (ESC) guidelines, irrespective of HAS-BLED. ResultsWe included 41,455 patients; 31.9% actually received warfarin. The expected treatment rate with the model ranged from 21% to 87% according to the version used. The model version resulting into the highest treatment rate (i.e. treating any patient with CHA2DS2-VASc ≥1) was associated with the greatest net benefit (0.98; 95% credible interval 0.72–1.23), compared with the actual practice, with a 1/3 reduction in overall mortality, as with the adoption of ESC guidelines. ConclusionsPreliminarily to a randomized impact study, our analysis suggests that individualizing anticoagulation for AF using a decisional model might have a clinical advantage over actual practice, and no added advantage over following ESC guidelines.

Impact of routine transoesophageal echocardiography on safety, outcomes, and cost of pulmonary vein ablation: inferences drawn from a decision analysis model

The practice of routine vs. selective transoesophageal echocardiography (TEE) surveillance for left atrial appendage or intracavitary thrombus prior to pulmonary vein isolation (PVI) varies widely as evidence to guide this decision in terms of important clinical outcomes is lacking. We constructed a decision analysis model to compare the cost-effectiveness of routine TEE for detection of left atrial thrombus vs. no TEE. The model incorporated health outcomes and costs. Markov methodology was used to follow patients as they transition through varying health states. We examined a hypothetical cohort of patients with symptomatic atrial fibrillation suitable for PVI, and expected outcomes were modelled over a period of 2 years. Simulated patients (SPs) undergoing a strategy of a routine TEE experienced significantly fewer transient ischemic attacks (TIAs) [OR 0.28 (0.22-0.37)], and debilitating strokes [OR 0.23 (0.15-0.33)]. Routine TEE led to an absolute risk reduction for stroke of 1.2% [number needed to treat (NNT) 84 (79-100)] and 1.9% for TIA [NNT 53 (48-59)]. The incremental cost-effectiveness ratio (ICER) for TEE was $226,608 per quality-adjusted life year (QALY). The ICER for TEE among high-risk SPs, with pre-existing clot in the left atrium, was $2232 per QALY. Decision analysis and microsimulation suggest that routine use of TEE in an unselected population prior to PVI lowers the incidence of cerebral thrombo-embolic events but with considerable cost per QALY.

Role of aspirin in tuberculous meningitis: A randomized open label placebo controlled trial

ObjectiveTo evaluate the efficacy and safety of aspirin in preventing stroke and mortality in tuberculous meningitis (TBM). MethodsPatients with TBM diagnosed on the basis of clinical, MRI and cerebrospinal fluid (CSF) criteria were randomized into aspirin 150mg daily or placebo. All the patients received four drug antitubercular treatment- RHZE (rifampicin, isoniazide, pyrazinamide and ethambutol) with or without corticosteroid. The primary endpoint was MRI proven stroke at 3months and secondary end points were mortality and functional outcome assessed by Barthel Index score at 3months. The adverse drug reactions were also analyzed. Results118 TBM patients were randomized into aspirin and placebo groups. The baseline demographic, clinical (severity of meningitis, MRI and CSF changes) were not significantly different between the two groups. 19 (16.1%) patients lost from follow up. 21 (33.3%) patients developed stroke after randomization which was insignificantly lesser in aspirin (24.2%) compared to the placebo group (43.3%; OR 0.42, 95%CI 0.12-1.39). Aspirin resulted in absolute risk reduction of stroke in 19.1% and significant reduction in mortality compared to placebo (21.7% Vs 43.4%, P=0.02). On binary logistic regression analysis, the age (OR 1.09, CI 1.03-1.14, P=0.001) was the only independent risk factor of stroke and aspirin was significantly related to survival (OR 3.17, 95% CI 1.21-8.31). Aspirin was well tolerated and was not withdrawn in any patient because of side effects. InterpretationAspirin resulted in insignificantly lesser strokes and significantly reduced 3month mortality in patients with TBM.

Evidence-Based Medicine, Conscience-Based Medicine, and the Management of Low-Risk Prostate Cancer

Evidence-Based Medicine, Conscience-Based Medicine, and the Management of Low-Risk Prostate Cancer

Evaluation and Management of Atrial Fibrillation

Atrial fibrillation (AF) is the most common clinically encountered arrhythmia affecting 0.4% of the general population. Its prevalence increases with age, affecting more than 6% of people over 80 years of age. The annual risk of ischemic stroke in patients with lone AF is approximately 1.3%. This annual risk increases up to 10% -12% in patients with a prior stroke or transient ischemic attack. Randomized clinical trials (RCT) comparing adjusted-dose oral anticoagulation and placebo showed a risk reduction of 61% (95% CI 47% to 71%). The absolute risk reduction for stroke with oral anticoagulants is about 3% per year. Aspirin has been shown in meta-analyses to have on average a 20-25% relative risk reduction, and is inferior to oral anticoagulants. In high risk patients with AF warfarin is a class I ACC/AHA indication unless there is a contraindication for anticoagulation. Unfortunately, this therapy requires frequent monitoring with blood samples and the interaction with food and several medications makes its use difficult and sometimes unreliable. It requires strict patient compliance and its use is also linked to potentially serious bleeding complications. In clinical practice, less than 60% of patients who do not have contraindications to oral anticoagulation are actually receiving them. Additionally, of those that receive oral anticoagulation, less than 50% are consistently within therapeutic targets. As such, the "real world" efficacy of a strategy towards prescribing oral anticoagulants is likely significantly lower than that demonstrated in clinical trials. As such, the need to discover other methods of anticoagulation with oral bioavailability, predictable pharmacokinetics, and minimal interactions with diet and other pharmacological agents is imperative. Low molecular weight heparin has a more predictable bioavailability and a longer half-life, but its subcutaneous mode of administration and long-term risks, in particular, osteoporosis makes the chronic use of this medication non-feasible. Antiplatelet agents such as clopidogrel have proven efficacy and superiority compared to aspirin to prevent systemic vascular events in at-risk patient populations, but currently they do not play an important role in the prevention of AF related thromboembolic events. The ACTIVE study is a randomized trial comparing the combination of clopidogrel and aspirin therapy to oral anticoagulation with warfarin in patients with AF, and was unfortunately terminated prematurely by the data safety and monitoring board because of increased events in the antiplatelet arm. Direct thrombin inhibitors, such as ximelagatran, may be as effective as warfarin for stroke-risk reduction in patients with AF. No anticoagulation monitoring is needed and it has excellent bioavailability, with a twice-daily oral dose. Elevation of liver enzymes was an initial concern regarding the use of this new drug, which is not available for general use. Ongoing pharmacological research and future clinical trials may one day leave the "warfarin days" behind. Unfortunately, the new therapies that are being tested seem to be at least several years away from being available on a widespread basis. In this review, we discuss the underlying pathophysiology of AF and stroke. We also provide a comprehensive discussion regarding various available therapies to treat AF.

Reporting Standards for Carotid Artery Angioplasty and Stent Placement

Reporting Standards for Carotid Artery Angioplasty and Stent Placement