Some of the risk factors for anticoagulation-related bleeding are also indications for the use of anticoagulants in AF patients .
Atrial fibrillation ( AF ) is associated with an increased stroke risk that may be reduced by therapeutic anticoagulation .
However , anticoagulation is associated with an increased risk of bleeding that in some patients may outweigh the benefits in reducing the risk of stroke .
Advanced Age, Anticoagulation Intensity, and Risk for Intracranial Hemorrhage among Patients Taking Warfarin for Atrial Fibrillation
Context The appropriate level of warfarin anticoagulation in elderly patients with atrial fibrillation has been debated because of an age-associated increase in intracerebral hemorrhage . Contribution Patients with atrial fibrillation and intracerebral hemorrhage who were receiving anticoagulation were matched with similar patients who did not develop intracerebral hemorrhage . Although intracerebral hemorrhage was associated with increasing age ( especially > 85 years ) and increasing international normalized ratios ( INRs ) ( especially > 3.5 ) , the incidence of intracerebral hemorrhage was not statistically different in patients with INRs less than 2.0 and those with INRs between 2.0 and 3.0 . This was true even among those older than 75 years of age . Implication s Risk for intracerebral hemorrhage is not diminished in elderly patients with atrial fibrillation when anticoagulation is maintained below an INR of 2.0 . The Editors Intracranial hemorrhage is the most dangerous complication of warfarin anticoagulant therapy because of its high short-term risk for death and severe neurologic deficit ( 1 - 5 ) . Warfarin is extremely effective in reducing the risk for ischemic stroke associated with atrial fibrillation ( 6 , 7 ) . However , fear of hemorrhage may prompt some physicians to avoid prescribing anticoagulation ( 8) , especially in elderly patients , who appear to have a higher risk for hemorrhage ( 8 - 13 ) . Prominent recent guidelines recommend using lower-intensity anticoagulation for the primary prevention of stroke in patients older than 75 years of age who have atrial fibrillation ( 14 ) and suggest a target international normalized ratio ( INR ) range of 1.6 to 2.5 , despite evidence that the risk for ischemic stroke increases sharply at INRs less than 2.0 ( 15 , 16 ) . Previous studies have not thoroughly addressed the relationship of age and anticoagulation intensity to the risk for intracranial hemorrhage among patients with atrial fibrillation ( 1 , 2 ) . A study of 121 patients with warfarin-associated intracranial hemorrhage used the now-out date d prothrombin time ratio as a measure of anticoagulation intensity and did not specifically address risk in patients with atrial fibrillation ( 1 ) . Earlier studies also included patients receiving anticoagulation for mechanical valves , whose risk-to-benefit ratio is different from that of patients with atrial fibrillation ( 1 , 2 , 17 ) . As the number of individuals with atrial fibrillation increases ( 18 - 21 ) and as a greater proportion of older adults receive anticoagulant therapy ( 22 ) , more precise data are needed about the association of age , INR , and risk for intracranial hemorrhage . Intracranial hemorrhage , although critically important , is an uncommon complication among patients with atrial fibrillation who are receiving anticoagulation . As a result , r and omized trials and cohort studies have difficulty accumulating enough hemorrhage events to powerfully assess risk factors . To address these limitations , we performed a large casecontrol study to evaluate the relationship of increasing age and INR to the risk for intracranial hemorrhage among patients with nonvalvular atrial fibrillation . Methods Case- Patients We performed a casecontrol study comparing 2 groups : 1 ) case- patients with nonvalvular atrial fibrillation who developed intracranial hemorrhage while taking warfarin and 2 ) controls who were receiving anticoagulation for nonvalvular atrial fibrillation but did not develop intracranial hemorrhage . We found potential case- patients using the Partners HealthCare System Research Patient Data Registry , which can identify patients with specific International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) diagnoses by search ing the Massachusetts General Hospital billing system . We search ed for patients 18 years of age or older who had diagnoses of atrial fibrillation ( ICD-9-CM code 427.31 ) and intracranial hemorrhage ( ICD-9-CM codes 430 , 431 , 432.0 , 432.1 , 432.9 ) at any time from October 1993 to June 2002 . By 1993 , nearly all prothrombin time ratios at the hospital were reported as INRs . We review ed medical records to confirm whether patients were eligible , that is , whether they had intracranial hemorrhage documented by computed tomography or magnetic resonance imaging and documentation of warfarin therapy for atrial fibrillation at the time of the event . We excluded patients who were not taking warfarin at the time of hemorrhage ; those who were receiving anticoagulation for rheumatic heart disease , mitral stenosis , or mechanical valve placement ; those whose event was an ischemic stroke with hemorrhagic conversion ; or those in whom clinical factors may have led to hemorrhage independent of warfarin therapy . These factors included underlying anatomic brain abnormalities ( such as tumors or aneurysms ) , antecedent major head trauma ( skull fracture , trauma with loss of consciousness , motor vehicle injury , or neurosurgical procedures ) , or platelet count less than 50 109 cells/L. Starting in July 1994 , consecutive patients with intracerebral hemorrhage have been enrolled through the Massachusetts General Hospital emergency department as part of a longitudinal cohort study ( 23 ) . To vali date our automated search strategy , we compared our case-patient list with the list of patients identified through the cohort study and found that our search strategy missed only 4 patients with intracerebral hemorrhage . We obtained data on patient date of birth , sex , and ethnicity from computerized records . The type of hemorrhage ( intracerebral , subdural , subarachnoid , intraventricular , or epidural ) was determined through review of radiology reports . Data on presenting symptoms , history of minor head trauma , concomitant aspirin use , and disposition status were obtained from review of the admission medical record and were recorded on a st and ardized data collection form . We recorded the INR measurement obtained closest to the onset of symptoms . If an INR was not available or fresh frozen plasma or vitamin K was administered before the measurement , we considered INR data missing . We review ed medical charts for documentation of the following comorbid conditions : history of cerebrovascular disease ( defined as previous ischemic stroke or carotid artery disease ) , hypertension , congestive heart failure , coronary artery disease , diabetes mellitus , and cancer ( excluding nonmelanoma skin cancer ) . Controls Controls were sample d from patients managed by the Massachusetts General Hospital Anticoagulation Management Services clinic , which followed approximately 1000 patients receiving anticoagulation for atrial fibrillation at any given time during the study period . All patients who were followed in the anticoagulation clinic , received anticoagulation for atrial fibrillation , and had an INR measurement obtained in the same month and year as the given case date were assigned a r and om number . Six controls per case-patient were then r and omly selected . We matched case- patients to controls by INR date to account for any technical changes in INR testing that may have occurred over time . Because of this sampling method , an individual patient could potentially serve as a control for more than 1 case-patient ( 24 ) . Like case- patients , controls were 18 years of age or older ; were receiving anticoagulation for atrial fibrillation ; and had no documented rheumatic heart disease , mitral stenosis , or valve replacement . We sought data on potential confounders of the association of age , INR , and risk for intracranial hemorrhage , focusing on relevant comorbid conditions and combined use of aspirin with warfarin . We review ed available computerized discharge summaries , outpatient clinic notes , and medication lists from up to 2 years before the admission date . If combination warfarin and aspirin use was not documented , patients were considered to not be taking aspirin . Statistical Analysis Case- patients were categorized by type of hemorrhage : intracerebral , subdural , and other ( subarachnoid , intraventricular , or epidural ) . Clinical differences between types of hemorrhage were compared by using the KruskalWallis test for continuous variables ( age and INR ) and chi-square tests for categorical variables . We compared case- patients with controls by using multivariable conditional logistic regression , matching on INR date . Patient age was divided into 5-year intervals that were coded as indicator variables , and the odds of intracranial hemorrhage for each interval were compared with the odds of hemorrhage at a referent age of 70 to 74 years . The INR was divided into a set of ordered intervals that were coded as indicator variables . The relative odds for intracranial hemorrhage at each interval were calculated by using an INR of 2.0 to 3.0 as the referent category . In addition to age , INR , sex , and ethnicity , the following variables were included in the multivariable models to control for potential confounding effects of clinical factors and aspirin use : cerebrovascular disease , hypertension , congestive heart failure , coronary artery disease , diabetes mellitus , cancer , and concomitant aspirin use . If no records were available for review , comorbid conditions and aspirin use were coded as missing . We used multiple imputations for missing data on ethnicity , comorbid conditions , and aspirin use ( 25 ) . We tested for interactions between age and INR and comorbid conditions using 2-way interactions . None of the interaction terms were included in the model if they were not statistically significant when tested collectively . We tested the model 's goodness of fit using the HosmerLemeshow method ( 26 ) . Because the hospital 's anticoagulation clinic did not follow some case- patients before the event , and since factors relating to differences in outpatient care and monitoring could have confounded our analyses , we repeated these analyses in the subgroup of case- patients managed by the anticoagulation clinic . These restricted analyses
Some of the risk factors for anticoagulation-related bleeding are also indications for the use of anticoagulants in AF patients .
Atrial fibrillation ( AF ) is associated with an increased stroke risk that may be reduced by therapeutic anticoagulation .
However , anticoagulation is associated with an increased risk of bleeding that in some patients may outweigh the benefits in reducing the risk of stroke .