Cerebral Microbleeds in Ischemic Stroke Patients on Warfarin Treatment

Örken, Dilek Neci̇oğlu; Kenangil, Gülay; Uysal, Ender; Forta, Hulki

doi:10.1161/strokeaha.109.559450

Cited by 43 publications

(27 citation statements)

References 17 publications

(10 reference statements)

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“…12,13 Compared with these clinical reports, our study now provides additional insight into the subclinical bleeding complications of oral coumarin anticoagulants in stroke-free persons. We also showed that the use of coumarin anticoagulants seemed to increase the risk of developing new microbleeds.…”

Section: Discussionmentioning

confidence: 85%

Use of Coumarin Anticoagulants and Cerebral Microbleeds in the General Population

Akoudad

Darweesh

Leening

et al. 2014

Stroke

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O ral coumarin anticoagulants are widely used to treat patients with (risk of) thromboembolic diseases. Bleeding is a serious adverse effect of all oral anticoagulants, 1 and intracerebral hemorrhages are among the most feared complications because of high morbidity and mortality rates. 2 Analogous to the increased risk of intracerebral hemorrhage, 3 it is conceivable that oral coumarin anticoagulants also increase the frequency of smaller, subclinical hemorrhages. These so-called cerebral microbleeds are recognized as hypointense foci on brain MRI and are thought to represent hemosiderin depositions. 4 In the population-based Rotterdam Study we investigated, first, whether coumarin users had a higher prevalence and incidence of microbleeds compared with never users. Second, we studied whether microbleeds were more frequent in participants with a higher maximum international normalized ratio (INR) value. Third, among coumarin users, we studied whether variability in INR was associated with microbleed presence. MethodsA detailed description of the Methods can be found in the online-only Data Supplement. The study was conducted within the population-based Rotterdam Study. 5,6 Data on coumarin use were available in 4945 participants with a baseline MRI and in 3069 participants with follow-up MRI. We extracted the highest measured INR value before baseline brain MRI, as well as INR values measured in ≤10 consecutive visits after initiation of treatment to calculate INR variability. 7,8 Microbleeds were rated on a T2*-weighted gradient-recalled echo sequence. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). First, we investigated the association between coumarin use and microbleeds after adjusting for age, sex, and cardiovascular risk factors. Second, we investigated the relation between maximum INR values and microbleed presence cross-sectionally, after adjusting for age, sex, and duration of coumarin use.Background and Purpose-It remains undetermined whether the use of coumarin anticoagulants associates with cerebral microbleeds in the general population. We investigated whether (1) coumarin use relates to higher prevalence and incidence of microbleeds, (2) microbleeds are more frequent in people with higher maximum international normalized ratios (INRs), and (3) among coumarin users, variability in INR associates with microbleed presence. Methods-From the population-based Rotterdam Study, 4945 participants aged ≥45 years were included in the crosssectional analysis, and 3069 participants had follow-up brain MRI. Information on coumarin use was obtained from automated pharmacy records. Coumarin users were monitored, and INR values were measured in consecutive visits. Presence and location of microbleeds were rated on brain MRI. We investigated the association of coumarin use with microbleeds using multivariable logistic regression. Results-Overall, 8.6% had used coumarin anticoagulants before the first MRI and 5.9% before follow-up MRI. The prevalence of microblee...

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Section: Discussionmentioning

confidence: 85%

Use of Coumarin Anticoagulants and Cerebral Microbleeds in the General Population

Akoudad

Darweesh

Leening

et al. 2014

Stroke

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“…34 Our findings of a higher risk of anticoagulant-associated ICH in Asians, blacks, the elderly, and patients with a history of stroke and elevated blood pressure are consistent with other observational studies and schema for predicting an increased risk of major (intracranial and extracranial) hemorrhage among anticoagulated individuals in other populations, supporting the external validity of our results. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][35][36][37] The more novel findings from this study are the association of declining platelet count and albumin with an increased risk of ICH and the association of a history of heart failure and taking rivaroxaban (instead of warfarin) with a reduced risk of ICH.…”

Section: Our Results In Context With Other Studiesmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Entry and exit criteria of the stepwise selection was α<0.05. All variables in Table 1 were candidate variables for the models.…”

Section: Discussionmentioning

confidence: 99%

“…A limitation of our study is that we were unable to adjust for variables that may influence ICH risk but were not measured at baseline or at the time of ICH, such as the presence or absence of the apolipoprotein E2 or E4 allele, 4 CYP2C9 polymorphism, 18 cerebral leukoaraiosis, 12 cerebral microbleeds, 21,22 cerebrovascular pathology such as amyloid angiopathy, 21,22 creatinine clearance <30 mL/min, 20,25 and international normalized ratio at the time of ICH. 10 There is also the possibility of systematic differences in the ascertainment and diagnosis of cases of ICH among different centers and regions.…”

Section: Limitationsmentioning

confidence: 99%

“…[3][4][5][6] All-cause ICH in the anticoagulated population occurs at a rate of 0.2% to 1.0% per year [7][8][9] and has likewise been associated not only with increasing age and blood pressure but also with previous ischemic stroke, chronic kidney disease, the early period of anticoagulation use, higher intensity (ie, poorly controlled) anticoagulation, antiplatelet use in addition to anticoagulation, and brain imaging evidence of cerebral leukoaraiosis and microbleeds. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Difficulty arises in clinical practice, because the risk factors for ICH with anticoagulation are also risk factors for ischemic stroke that could be prevented with anticoagulation. A recent study suggests that increasing age and previous stroke are more often associated with ischemic stroke than with ICH, whereas a history of hypertension, diabetes mellitus, renal impairment, and alcohol intake are equally associated.…”

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confidence: 99%

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Intracranial Hemorrhage Among Patients With Atrial Fibrillation Anticoagulated With Warfarin or Rivaroxaban

Hankey

Stevens

Piccini

et al. 2014

Stroke

181

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Background and Purpose-Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation. Methods-WePredictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73). Conclusions-Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

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Current awareness: Pharmacoepidemiology and drug safety

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Pharmacoepidemiology and Drug

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 23 sections: 1 Reviews; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Teratogens/fetal exposure; 20 Antidiabetic Agents; 21 Contrast Agents; 22 Bone Conservation Agents; 23 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Cerebral Microbleeds in Ischemic Stroke Patients on Warfarin Treatment

Cited by 43 publications

References 17 publications

Use of Coumarin Anticoagulants and Cerebral Microbleeds in the General Population

Use of Coumarin Anticoagulants and Cerebral Microbleeds in the General Population

Intracranial Hemorrhage Among Patients With Atrial Fibrillation Anticoagulated With Warfarin or Rivaroxaban

Current awareness: Pharmacoepidemiology and drug safety

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