Differences Between Anticoagulated Patients With Ischemic Stroke Versus Intracerebral Hemorrhage

Background Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce. Methods and Results Cross‐sectional study was done on consecutive oral anticoagulant–treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel‐Oral‐Anticoagulants‐In‐Stroke‐Patients)‐Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32–0.82], 0.48 [0.26–0.86], 0.55 [0.34–0.89], and 0.82 [0.75–0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87–14.04], 1.37 [1.04–1.81] per 10 years, 1.19 [1.10–1.29] per 10 mm Hg, and 1.81 [1.09–3.03]). Cerebral microbleeds and moderate‐to‐severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34–6.18], and 2.62 [1.28–5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31–0.90], 0.29 [0.05–0.97], 0.48 [0.30–0.76], and 0.32 [0.13–0.67]). Conclusions In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02353585.

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A Comparison of a Moderate with Moderate-high Intensity Oral Anticoagulant Treatment in Patients with Mechanical Heart Valve Prostheses

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656064 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0839-0844 ◽

Cited By ~ 34

Author(s):

Vittorio Pengo ◽

Fabio Barbero ◽

Alberto Banzato ◽

Elisabetta Garelli ◽

Franco Noventa ◽

...

Keyword(s):

Heart Valve ◽

High Intensity ◽

Oral Anticoagulant ◽

Oral Anticoagulants ◽

Mechanical Heart Valve ◽

Moderate Intensity ◽

Minor Bleeding ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment ◽

Valve Prostheses

SummaryBackground. The long-term administration of oral anticoagulants to patients with mechanical heart valve prostheses is generally accepted. However, the appropriate intensity of oral anticoagulant treatment in these patients is still controversial.Methods and Results. From March 1991 to March 1994, patients referred to the Padova Thrombosis Center who had undergone mechanical heart valve substitution at least 6 months earlier were randomly assigned to receive oral anticoagulants at moderate intensity (target INR = 3) or moderate-high intensity (target INR = 4). Principal end points were major bleeding, thromboembolism and vascular death. Minor bleeding was a secondary end-point.A total of 104 patients were assigned to the target 3 group and 101 to the target 4 group; they were followed for from 1.5 years to up 4.5 years (mean, 3 years). Principal end-points occurred in 13 patients in the target 3 group (4 per 100 patient-years) and in 20 patients in the target 4 group (6.9 per 100 patient-years). Major hemorrhagic events occurred in 15 patients, 4 in the target 3 group (1.2 per 100 patient-years) and 11 in the target 4 group (3.8 per 100 patient-years) (p = 0.019). The 12 recorded episodes of thromboembolism, 4 of which consisted of a visual deficit, were all transient ischemic attacks, 6 in the target 3 group (1.8 per 100 patient-years) and 6 in the target 4 group (2.1 per 100 patient- years). There were 3 vascular deaths in each group (0.9 and 1 per 100 patient-years for target 3 and target 4 groups, respectively). Minor bleeding episodes occurred 85 times (26 per 100 patient-years) in the target 3 group and 123 times (43 per 100 patient-years) in the target 4 group (p = 0.001).Conclusions. Mechanical heart valve patients on anticoagulant treatment who had been operated on at least 6 months earlier experienced fewer bleeding complications when maintained on a moderate intensity regimen (target INR = 3) than those on a moderate-high intensity regimen (target INR = 4). The number of thromboembolic events and vascular deaths did not differ between the two groups.

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P4745Concomitant oral anticoagulant and antidepressant therapy in patients with atrial fibrillation and risk of stroke and bleeding: a population based cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz745.1121 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J J Komen ◽

P Hjemdahl ◽

A K Mantel - Teeuwisse ◽

O H Klungel ◽

B Wettermark ◽

...

Keyword(s):

Atrial Fibrillation ◽

Propensity Score ◽

Oral Anticoagulant ◽

Cox Regression ◽

Oral Anticoagulants ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment ◽

Increased Risk ◽

Antidepressant Use

Abstract Background Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. Antidepressants use is associated with increased risk for stroke and bleeds. Objective To assess the association between antidepressant use in AF patients with oral anticoagulants and bleeding and stroke risk. Methods All AF patients newly prescribed with an oral anticoagulant in the Stockholm Healthcare database (n=2.3 million inhabitants) from July 2011 until 2016 were included and followed for one year or shorter if they stopped claiming oral anticoagulant treatment or had an outcome of interest. Outcomes were severe bleeds and strokes, requiring acute hospital care. During follow-up, patients were considered exposed to antidepressant after claiming a prescription for the duration of the prescription. With a time-varying Cox regression, we assessed the association between antidepressant use and strokes and bleeds, adjusting for confounders (i.e., age, sex, comorbidities, comedication, and year of inclusion). In addition, we performed a propensity score matched analysis to test the robustness of our findings. Results Of the 30,595 patients included after claiming a prescription for a NOAC (n=13,506) or warfarin (n=17,089), 4 303 claimed a prescription for an antidepressant during follow-up. A total of 712 severe bleeds and 551 strokes were recorded in the cohort. Concomitant oral anticoagulant and antidepressant use was associated with increased rates of severe bleeds (4.7 vs 2.7 per 100 person-years) compared to oral anticoagulant treatment without antidepressant use (aHR 1.42, 95% CI: 1.12–1.80), but not significantly associated with increased stroke rates (3.5 vs 2.1 per 100 person-years, aHR 1.23, 95% CI: 0.93–1.62). No significant differences were observed between different oral anticoagulant classes (i.e., warfarin or NOAC) or different antidepressant classes (i.e., SSRI, TCA, or other antidepressant). Additional propensity-score matched analyses yielded similar results but showed a significantly increased risk for stroke (HR: 1.47, 95% CI: 1.08–2.02). Incidence rates of strokes and bleeds Conclusion Concomitant use of an oral anticoagulant and an antidepressant, irrespective of type, is associated with an increased bleeding risk. Increased awareness and a critical consideration for the need of an antidepressant is recommended in this population. Acknowledgement/Funding Swedish Heart Lung Foundation

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THE THROMBOTIC COMPLICATIONS OF TWO GROUPS OF PATIENTS WITH DIFFERENT INR THERAPEUTIC RANGES. THE NECESSITY OF INTENSE ORAL ANTICOAGULANT TREATMENT

10.1055/s-0038-1643263 ◽

1987 ◽

Author(s):

Ir Kontopoulou-Griva ◽

J Spiliotopoulou ◽

L Digenopoulou ◽

J Georgopoulos

Keyword(s):

High Risk ◽

Oral Anticoagulant ◽

Heart Valves ◽

Oral Anticoagulants ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment ◽

Daily Dose ◽

Group A ◽

Thrombotic Complications ◽

Group B

One of the reasons why oral anticoagulants fell into disrepute is the absence of internationally acceptable standarised procedures for controlling the level of anticoagulation. This deplorable situation resulted in over and under coagulation and uncertainty in the therapeutic range. The International Normalised Ratio (INR) can safely be applied in patients on oral anticoagulants.We present two Groups of patients under long term anti coagulation, mainly because of prosthetic heart valves that have recently been added to our outpatients clinic. These patients were till then attended by two cardiologists with different attitudes on the intensity of the anticoagulant treatment. The thromboplastin reagent used is that of ox origin and the results are expressed on INR.The Group A with 32 patients had at the time that we started attending them an INR x = 1,80 ± 0,48 and a daily dose of acenocoumarol x = 1,65 ± 0,51.The Group B with 49 patients had an INR x = 2,75 ± 0,51 and a daily dose of acenocoumarol x = 2,52 ± 1,53.Seven patients of the Group A referred thrombotic complications, while three patients of the Group B referred transiant thrombotic complications.The statistical analysis with the t-test of the INR between the two Groups is p<0,001 while that of the thrombotic complication with the x2 is p<0,05.The introduction of the INR and the acceptance by the medical people of the necessity of the intense oral anticoagulant treatment especially on high risk patients with mechanical heart valves as is the majority of the presented patients, will minimize the thromboembolic complications without high risk of bleeding.

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PROTEIN C RESPONSE TO INDUCTION AND WITHDRAWAL OF ORAL ANTICOAGULANT TREATMENT

10.1055/s-0038-1643273 ◽

1987 ◽

Author(s):

K P Schofield ◽

J M Thomson ◽

L Poller

Keyword(s):

Oral Anticoagulant ◽

Protein C ◽

Oral Anticoagulants ◽

Factor Vii ◽

Factor X ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment ◽

Rate Of Increase ◽

Long Term Treatment

Protein C (PC) activity and antigen levels have been related to clotting activities of factors VII and X during the induction and withdrawal periods of oral anticoagulant treatment. Both factor VII and PC activities fell rapidly during a gradual induction regime of nicoumalone in six consecutive patients but factor VII showed a more rapid and much more marked depression than PC. In contrast reductions in factor X were much slower. PC antigen although depressed rapidly at the initiation of treatment did not subsequently fall to the same degree as PC activity, The ratio of activity to antigen became progressively smaller.In six further serial patients discontinued from long-term treatment with nicoumalone (mean duration 12-6 months) there was a reversal of the pattern, but with two important differences. Firstly, there was evidence of an excessive rise (“rebound”) of factor VII compared with the steady state levels in these patients; and secondly there was an unexpectedly slow return of PC activity and antigen to normal levels after the oral anticoagulant was withdrawn (levels were still below normal on day 4). Factor X also showed a slow rate of increase, similar to PC activity recovery. These observations lend support to gradual withdrawal of oral anticoagulants after a period of long-term administration. The results suggest that after discontinuation of long-term oral anticoagulants patients may have increased coagulability up to four days.

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Protocol for MAAESTRO: Electronic Monitoring and Improvement of Adherence to Direct Oral Anticoagulant Treatment—A Randomized Crossover Study of an Educational and Reminder-Based Intervention in Ischemic STROke Patients Under Polypharmacy

Frontiers in Neurology ◽

10.3389/fneur.2018.01134 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Alexandros A. Polymeris ◽

Valerie Albert ◽

Kurt E. Hersberger ◽

Stefan T. Engelter ◽

Sabine Schaedelin ◽

...

Keyword(s):

Ischemic Stroke ◽

Crossover Study ◽

Oral Anticoagulant ◽

Electronic Monitoring ◽

Direct Oral Anticoagulant ◽

Anticoagulant Treatment ◽

Stroke Patients ◽

Oral Anticoagulant Treatment ◽

Randomized Crossover Study

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IS APPROPRIATE USE OF ORAL ANTICOAGULANTS IMPROVING AMONG ATRIAL FIBRILLATION PATIENTS? RESULTS FROM THE BENCHMARKING AN ORAL ANTICOAGULANT TREATMENT RATE IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION (BOAT-AF) STUDY AND COMPARISON TO 387,975 PARTICIPANTS IN THE PINNACLE REGISTRY®

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)03165-x ◽

2021 ◽

Vol 77 (18) ◽

pp. 1809

Author(s):

Joseph Kim ◽

Jane Lee ◽

Julie Sutherland ◽

Clifford Ehrlich ◽

Ravinder Bachireddy ◽

...

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulant ◽

Oral Anticoagulants ◽

Anticoagulant Treatment ◽

Treatment Rate ◽

Appropriate Use ◽

Nonvalvular Atrial Fibrillation ◽

Oral Anticoagulant Treatment

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Intracranial Internal Carotid Artery Calcification Is Not Predictive of Future Cognitive Decline

10.21203/rs.3.rs-910476/v1 ◽

2021 ◽

Author(s):

Farzaneh Rahmani ◽

Marina Nguyen ◽

Charles D. Chen ◽

Nicole McKay ◽

Aylin Dincer ◽

...

Keyword(s):

Carotid Artery ◽

Internal Carotid ◽

Small Vessel Disease ◽

Calcium Score ◽

Hippocampal Volume ◽

Imaging Biomarkers ◽

Amyloid Burden ◽

Vessel Disease ◽

Future Risk

Abstract BackgroundIntracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICA calcification for future risk of dementia and compared the results with conventional imaging biomarkers of dementia.MethodsIn a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICA calcification was quantified on baseline CT scans using the Agatson calcium score. The ability of baseline ICA calcification to discriminate between a control group (participants who maintained a Clinical Dementia Rating (CDR™) score of zero over all follow-up visits) and a converter group (participants who had a baseline CDR of zero but received a persistent CDR>0 at any follow-up visit) was evaluated along with the predictive value of baseline ICA calcification for longitudinal clinical and imaging biomarkers. ResultsBaseline ICA calcium score could not distinguish participants who converted to CDR>0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICA calcification increased with age, male sex, and higher WMH volumes at baseline visit. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICA calcification was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume.ConclusionsIn elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICA calcification is not directly associated with a future risk of dementia, cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.

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Aspirin After Oral Anticoagulants for Prevention of Recurrence in Patients with Unprovoked Venous Thromboembolism. the Warfasa STUDY

Blood ◽

10.1182/blood.v118.21.543.543 ◽

2011 ◽

Vol 118 (21) ◽

pp. 543-543 ◽

Cited By ~ 3

Author(s):

Cecilia Becattini ◽

Giancarlo Agnelli ◽

Renzo Poggio ◽

Sabine Eichinger ◽

Eugenio Bucherini ◽

...

Keyword(s):

Venous Thromboembolism ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Conflicts Of Interest ◽

Low Cost ◽

Oral Anticoagulants ◽

Hazard Ratio ◽

Anticoagulant Treatment ◽

Double Blind ◽

Oral Anticoagulant Treatment

Abstract Abstract 543 Background A recurrence occurs in 15–20% of patients with unprovoked venous thromboembolism (VTE) in the two years after the withdrawal of oral anticoagulant treatment. Extending anticoagulant treatment is effective but associated with increased bleeding risk. We assessed the efficacy and safety of aspirin for the prevention of VTE recurrence after a conventional course of oral anticoagulation. Methods Warfasa was an investigator-initiated double-blind randomized placebo-controlled event-driven study. Patients with a first-ever unprovoked VTE who had completed 6–12 months of oral anticoagulant treatment were randomized to receive aspirin, 100 mg daily, or placebo for at least two years. The primary efficacy outcome was objectively confirmed recurrent symptomatic VTE and VTE-related death. Clinically relevant (major and non-major) bleeding were the main safety outcome. All outcome events were blindly adjudicated by an independent committee. Results A VTE recurrence occurred in 27 of the 205 patients who received aspirin and 42 of the 197 patients who received placebo (6.3% versus 11.0% patient-years; hazard ratio, 0.57, 95% CI 0.35 to 0.93) during the study period (mean 24 months) (Figure A). While on study treatment, 22 and 38 patients who received aspirin or placebo, respectively had a recurrence (5.7% versus 10.7% patient-years; hazard ratio, 0.54, 95% CI 0.32 to 0.91) (mean on-treatment period 22 months) (Figure B). One patient in each treatment group had a major bleeding, with a similar incidence of clinically relevant non-major bleeding. Conclusions Aspirin reduces by about 40% the risk of recurrence in patients with unprovoked VTE without increasing bleeding, when given after a 6–12 month anticoagulant treatment. For its safety, practicality and low cost, aspirin is a valid alternative to oral anticoagulants in the extended treatment of VTE. Disclosures: No relevant conflicts of interest to declare.

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