scholarly journals Using the Case-Crossover Design to Assess Short-Term Risks of Bleeding and Arterial Thromboembolism After Switching Between Oral Anticoagulants in a Population-Based Cohort of Patients With Atrial Fibrillation

2020 ◽  
Vol 189 (12) ◽  
pp. 1467-1477
Author(s):  
Maja Hellfritzsch ◽  
Shirley V Wang ◽  
Erik Lerkevang Grove ◽  
Joshua J Gagne ◽  
Jesper Hallas ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Confidence Intervals ◽  
Odds Ratio ◽  
Oral Anticoagulant ◽  
Conditional Logistic Regression ◽  
Population Based ◽  
Short Term ◽  
Arterial Thromboembolism ◽  
Case Crossover

Abstract Using nationwide Danish registries, we conducted a population-based case-crossover study evaluating the association between switching from a vitamin K antagonist (VKA) to a direct oral anticoagulant (DOAC), and vice versa, and 30-day risks of bleeding and arterial thromboembolism in patients with atrial fibrillation (AF). The case-crossover population was identified among oral anticoagulant users during 2011–2018 (n = 123,217) as patients with AF with 1) a case-defining outcome and 2) an anticoagulant switch during the 180 days preceding the outcome. Odds ratios were estimated using conditional logistic regression by comparing the occurrence of switching during the 30-day window immediately preceding the outcome to that in reference windows in the same individual 60–180 days before the outcome. The case-crossover populations for switching from VKA to DOAC and DOAC to VKA comprised 1,382 and 287 case patients, respectively. Switching from VKA to DOAC, but not from DOAC to VKA, was associated with an increased short-term risk of bleeding (odds ratio = 1.42; 95% confidence intervals: 1.13, 1.79, and 1.06; and 0.64, 1.75, respectively) and ischemic stroke (odds ratio = 1.74; 95% confidence intervals: 1.21, 2.51, and 0.92; and 0.46, 1.83, respectively). Our findings suggest that switching from VKA to DOAC is an intermittent risk factor of bleeding and ischemic stroke in patients with AF.

scholarly journals Assessing short-term risk of ischemic stroke in relation to all prescribed medications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imre Janszky ◽  
Ioannis Vardaxis ◽  
Bo Henry Lindqvist ◽  
Jens Wilhelm Horn ◽  
Ben Michael Brumpton ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Odds Ratio ◽  
Crossover Design ◽  
Lasso Regression ◽  
Short Term ◽  
Case Crossover ◽  
Increased Risk ◽  
Follow Up Studies ◽  
Prescription Databases

AbstractWe examined the short-term risk of stroke associated with drugs prescribed in Norway or Sweden in a comprehensive, hypothesis-free manner using comprehensive nation-wide data. We identified 27,680 and 92,561 cases with a first ischemic stroke via the patient- and the cause-of-death registers in Norway (2004–2014) and Sweden (2005–2014), respectively, and linked these data to prescription databases. A case-crossover design was used that compares the drugs dispensed within 1 to 14 days before the date of ischemic stroke occurrence with those dispensed 29 to 42 days before the index event. A Bolasso approach, a version of the Lasso regression algorithm, was used to select drugs that acutely either increase or decrease the apparent risk of ischemic stroke. Application of the Bolasso regression algorithm selected 19 drugs which were associated with increased risk for ischemic stroke and 11 drugs with decreased risk in both countries. Morphine in combination with antispasmodics was associated with a particularly high risk of stroke (odds ratio 7.09, 95% confidence intervals 4.81–10.47). Several potentially intriguing associations, both within and across pharmacological classes, merit further investigation in focused, follow-up studies.

Abstract TP167: Short-Term Exposures to Ambient Air Pollution and Risk of Recurrent Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jeffrey J Wing ◽  
Sara D Adar ◽  
Brisa N Sanchez ◽  
Lewis B Morgenstern ◽  
Melinda A Smith ◽  
...  
Keyword(s):  
Air Pollution ◽  
Ischemic Stroke ◽  
Conditional Logistic Regression ◽  
Ambient Air ◽  
Population Based ◽  
Ambient Air Pollution ◽  
Stroke Recurrence ◽  
Short Term ◽  
Logistic Regression Models ◽  
Poor Outcomes

Background: Recurrent strokes are associated with poor outcomes and mortality. Short-term ambient air pollution may be an important environmental risk factor for stroke recurrence. Although associations between air pollution and stroke risk have been observed, the evidence for short-term effects of air pollution on risk of stroke recurrence is in its infancy. We investigated the association between short-term changes in ambient pollution (particulate matter <2.5μm (PM 2.5 ) and ozone (O 3 )) and the risk of recurrent ischemic stroke among individuals living in a bi-ethnic community. Methods: We identified recurrent ischemic stroke cases from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) Project, an ongoing population-based stroke surveillance study in Nueces County, Texas, between 2000 and 2012. Associations between lags of 0 to 3 days PM 2.5 and O 3 levels and odds of ischemic stroke were assessed using a time-stratified case-crossover design. Conditional logistic regression models were used to calculate odds ratios (ORs) for a 10 unit change in exposure. Results: There were 317 recurrent ischemic strokes with mean age of 72 years (SD=12). Median levels of PM 2.5 and O 3 over the study period were 7.7μg/m 3 (IQR: 5.6-10.7μg/m 3 ) and 35.2ppb (IQR: 25.0-46.1ppb), respectively. No associations were observed across the different lagged exposures (0 to 3 days) after adjusting for ambient temperature and relative humidity (Figure). Co-adjustment of both pollutants results did not change the results. Conclusion: No association between PM 2.5 and O 3 and risk of recurrences was observed. Research on the influence of air pollutants on risk of recurrence is still in its infancy, and more research is needed to understand the relation.

scholarly journals Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation

Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2347-2354
Author(s):  
Michela Giustozzi ◽  
Monica Acciarresi ◽  
Giancarlo Agnelli ◽  
Valeria Caso ◽  
Fabio Bandini ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Vitamin K ◽  
Major Bleeding ◽  
Odds Ratio ◽  
Oral Anticoagulant ◽  
Primary Outcome ◽  
Oral Anticoagulants ◽  
Early Recurrence

Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50–1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53–2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation–related acute ischemic stroke, who started on oral anticoagulant.

Abstract TP416: Comparative Effectiveness of Addition of Antiplatelet to Oral Anticoagulant in Acute Ischemic Stroke With Atrial Fibrillation

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Joon-tae Kim ◽  
Hee-Joon Bae ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Oral Anticoagulant ◽  
Recurrent Stroke ◽  
Cox Proportional Hazards ◽  
Large Artery ◽  
Vascular Events ◽  
Nihss Score ◽  
Composite Events

Introduction: Atrial fibrillation (AF) and large artery diseases (LAD) share several risk factors and often coexist in the same patient. Optimal treatments for acute ischemic stroke (AIS) patients with concomitant AF and LAD have not been extensively studied so far. Objective: This study aimed to compare the effectiveness of the addition of antiplatelet (AP) to oral anticoagulant (OAC) with that of OAC alone in AIS with AF according to the LAD. Methods: Using a multicenter stroke registry, acute (within 48h of onset) and mild-to-moderate (NIHSS score ≤15) stroke patients with AF were identified. Propensity scores using IPTW were used to adjust baseline imbalances between the OAC+AP group and the OAC alone group in all patients and in each subgroup by LAD. The primary outcome was major vascular events, defined as the composite of recurrent stroke, MI, and all-cause mortality at up to 3 months after index stroke. Results: Among the 5469 patients (age, 72±10yrs; male, 54.9%; initial NIHSS score, 4 [2-9]), 79.0% (n=4323) received OAC alone, and 21.0% (n=1146) received OAC+AP. By weighted Cox proportional hazards analysis, a tendency of increasing the risk of 3-months primary composite events in the OAC+AP group vs the OAC alone (HR 1.36 [0.99-1.87], p=0.06), with significant interaction with treatments and LAD (Pint=0.048). Briefly, among patients with moderate-to-severe large artery stenosis, tendency of decrease in 3-months primary composite events of the OAC+AP group, compared with OAC alone group, was observed (HR 0.54 [0.17-1.70]), whereas among patients with complete occlusion, the OAC+AP group markedly increased the risk of 3-months composite events (HR 2.00 [1.27-3.15]), compared with the OAC alone group. No interaction between direct oral anticoagulant and warfarin on outcome was observed (Pint=0.35). Conclusion: In conclusion, treatment with addition of AP to OAC had a tendency to increase the risk of 3-months vascular events, compared with OAC alone in AIS with AF. However, the effects of antithrombotic treatment could be modified according to the LAD, with substantial benefits of OAC alone in subgroup of large artery occlusion. Our results address the need for the further study to tailor the optimal treatment in AIS with concomitant AF and LAD.

scholarly journals Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study

2017 ◽  
Vol 176 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Olaf M Dekkers ◽  
Erzsébet Horváth-Puhó ◽  
Suzanne C Cannegieter ◽  
Jan P Vandenbroucke ◽  
Henrik Toft Sørensen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Cardiovascular Events ◽  
Population Based ◽  
Arterial Embolism ◽  
Registration System ◽  
Increased Risk ◽  
All Cause Mortality

Objective Several studies have shown an increased risk for cardiovascular disease (CVD) in hyperthyroidism, but most studies have been too small to address the effect of hyperthyroidism on individual cardiovascular endpoints. Our main aim was to assess the association among hyperthyroidism, acute cardiovascular events and mortality. Design It is a nationwide population-based cohort study. Data were obtained from the Danish Civil Registration System and the Danish National Patient Registry, which covers all Danish hospitals. We compared the rate of all-cause mortality as well as venous thromboembolism (VTE), acute myocardial infarction (AMI), ischemic and non-ischemic stroke, arterial embolism, atrial fibrillation (AF) and percutaneous coronary intervention (PCI) in the two cohorts. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated. Results The study included 85 856 hyperthyroid patients and 847 057 matched population-based controls. Mean follow-up time was 9.2 years. The HR for mortality was highest in the first 3 months after diagnosis of hyperthyroidism: 4.62, 95% CI: 4.40–4.85, and remained elevated during long-term follow-up (>3 years) (HR: 1.35, 95% CI: 1.33–1.37). The risk for all examined cardiovascular events was increased, with the highest risk in the first 3 months after hyperthyroidism diagnosis. The 3-month post-diagnosis risk was highest for atrial fibrillation (HR: 7.32, 95% CI: 6.58–8.14) and arterial embolism (HR: 6.08, 95% CI: 4.30–8.61), but the risks of VTE, AMI, ischemic and non-ischemic stroke and PCI were increased also 2- to 3-fold. Conclusions We found an increased risk for all-cause mortality and acute cardiovascular events in patients with hyperthyroidism.

scholarly journals A novel weighting method to remove bias from within-subject exposure dependency in case-crossover studies

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kiyoshi Kubota ◽  
Thu-Lan Kelly ◽  
Tsugumichi Sato ◽  
Nicole Pratt ◽  
Elizabeth Roughead ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crossover Study ◽  
Odds Ratio ◽  
Time Trends ◽  
Rate Ratio ◽  
Conditional Logistic Regression ◽  
Time Varying ◽  
Weighting Method ◽  
Case Crossover ◽  
Crossover Studies

Abstract Background Case-crossover studies have been widely used in various fields including pharmacoepidemiology. Vines and Farrington indicated in 2001 that when within-subject exposure dependency exists, conditional logistic regression can be biased. However, this bias has not been well studied. Methods We have extended findings by Vines and Farrington to develop a weighting method for the case-crossover study which removes bias from within-subject exposure dependency. Our method calculates the exposure probability at the case period in the case-crossover study which is used to weight the likelihood formulae presented by Greenland in 1999. We simulated data for the population with a disease where most patients receive a cyclic treatment pattern with within-subject exposure dependency but no time trends while some patients stop and start treatment. Finally, the method was applied to real-world data from Japan to study the association between celecoxib and peripheral edema and to study the association between selective serotonin reuptake inhibitor (SSRI) and hip fracture in Australia. Results When the simulated rate ratio of the outcome was 4.0 in a case-crossover study with no time-varying confounder, the proposed weighting method and the Mantel-Haenszel odds ratio reproduced the true rate ratio. When a time-varying confounder existed, the Mantel-Haenszel method was biased but the weighting method was not. When more than one control period was used, standard conditional logistic regression was biased either with or without time-varying confounding and the bias increased (up to 8.7) when the study period was extended. In real-world analysis with a binary exposure variable in Japan and Australia, the point estimate of the odds ratio (around 2.5 for the association between celecoxib and peripheral edema and around 1.6 between SSRI and hip fracture) by our weighting method was equal to the Mantel-Haenszel odds ratio and stable compared with standard conditional logistic regression. Conclusion Case-crossover studies may be biased from within-subject exposure dependency, even without exposure time trends. This bias can be identified by comparing the odds ratio by the Mantel-Haenszel method and that by standard conditional logistic regression. We recommend using our proposed method which removes bias from within-subject exposure dependency and can account for time-varying confounders.

scholarly journals Trends in initiation of direct oral anticoagulant therapies for atrial fibrillation in a national population-based cross-sectional study in the French health insurance databases

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e018180 ◽  
Author(s):  
Laetitia Huiart ◽  
Cyril Ferdynus ◽  
Christel Renoux ◽  
Amélie Beaugrand ◽  
Sophie Lafarge ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Multivariate Analysis ◽  
National Health ◽  
Oral Anticoagulant ◽  
Vitamin K Antagonists ◽  
Population Based ◽  
Administrative Database ◽  
Direct Oral Anticoagulant ◽  
Health Authorities ◽  
First Choice

ObjectiveUnlike several other national health agencies, French health authorities recommended that the newer direct oral anticoagulant (DOAC) agents only be prescribed as second choice for the treatment of newly diagnosed non-valvular atrial fibrillation (NVAF), with vitamin K antagonists (VKA) remaining the first choice. We investigated the patterns of use of DOACs versus VKA in the treatment of NVAF in France over the first 5 years of DOAC availability. We also identified the changes in patient characteristics of those who initiated DOAC treatment over this time period.MethodsBased on the French National Health Administrative Database, we constituted a population-based cohort of all patients who were newly treated for NVAF between January 2011 and December 2015. Trends in drug use were described as the percentage of patients initiating each drug at the time of treatment initiation. A multivariate analysis using logistic regression model was performed to identify independent sociodemographic and clinical predictors of initial anticoagulant choice.ResultsThe cohort comprised 814 446 patients who had received a new anticoagulant treatment for NVAF. The proportion of patients using DOACs as initial anticoagulant therapy reached 54% 3 months after the Health Ministry approved the reimbursement of dabigatran for NVAF, and 61% by the end of 2015, versus VKA use. In the multivariate analysis, we found that DOAC initiators were younger and healthier overall than VKA initiators, and this tendency was reinforced over the 2011–2014 period. DOACs were more frequently prescribed by cardiologists in 2012 and after (adjusted OR in 2012: 2.47; 95% CI 2.40 to 2.54).ConclusionDespite recommendations from health authorities, DOACs have been rapidly and massively adopted as initial therapy for NVAF in France. Observational studies should account for the fact that patients selected to initiate DOAC treatment are healthier overall, as failure to do so may bias the risk–benefit assessment of DOACs.

The choice of an oral anticoagulant

1972 ◽  
Vol 10 (7) ◽  
pp. 25-28 ◽  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Anticoagulant Therapy ◽  
Cerebral Ischaemia ◽  
Oral Anticoagulant ◽  
Short Term ◽  
Prevention And Treatment ◽  
Transient Cerebral Ischaemia

Some of the indications for anticoagulant therapy remain controversial, but they are widely used for the prevention and treatment of thrombosis and embolism after surgery1 and after myocardial infarction,2 in patients with atrial fibrillation, and in those with transient cerebral ischaemia.3 This article discusses the drugs available for long-term use. Those suitable for immediate and short-term use, heparin and arvin, will be discussed in the next issue.

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