Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2.

BACKGROUND: Vitamin K allows for gamma-carboxylation of glutamyl residues, a conversion that activates clotting factors and bone proteins. Vitamin K antagonists such as warfarin inhibit this process. Our goal was to quantify the association between warfarin and osteoporotic fractures in patients with atrial fibrillation. METHODS: This was a retrospective cohort study of Medicare beneficiaries with atrial fibrillation who were hospitalized between March 1998 and April 1999 in all 50 US states. The study outcome was osteoporotic fractures, identified by an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for a fracture of the hip, spine, or wrist. RESULTS: Compared with 7587 patients who were not prescribed warfarin, the adjusted odds ratio (OR) of fracture was 1.25 (95% confidence interval [CI], 1.06-1.48) in 4461 patients prescribed long-term warfarin therapy (> or = 1 year). The association between osteoporotic fracture and long-term warfarin use was significant in men (OR, 1.63; 95% CI, 1.26-2.10) but nonsignificant in women (OR, 1.05; 95% CI, 0.88-1.26). In 1833 patients prescribed warfarin for less than a year, the risk of osteoporotic fracture was not increased significantly (OR, 1.03). Odds ratios (95% CIs) of independent predictors of osteoporotic fractures were as follows: increasing age, 1.63 (1.47-1.80) per decade; high fall risk, 1.78 (1.42-2.21); hyperthyroidism, 1.77 (1.16-2.70); neuropsychiatric disease, 1.51 (1.28-1.78); and alcoholism, 1.50 (1.01-2.24). Factors with a reduced OR (95% CI) included African American race, 0.30 (0.18-0.51); male sex, 0.54 (0.46-0.62); and use of beta-adrenergic antagonists, 0.84 (0.70-1.00). CONCLUSIONS: Long-term use of warfarin was associated with osteoporotic fractures, at least in men with atrial fibrillation. Beta-adrenergic antagonists may protect against osteoporotic fractures.

Use and effectiveness of warfarin in Medicare beneficiaries with atrial fibrillation.

BACKGROUND AND PURPOSE: More than 2 million Americans have atrial fibrillation, and without antithrombotic therapy, their stroke rate is increased 5-fold. In randomized controlled trials, warfarin prevented 65% of ischemic strokes (hazard ratio [HR], 0.35; 95% CI, 0.26 to 0.48) compared with no antithrombotic therapy. However, the effectiveness of warfarin therapy outside of clinical trials is unknown, especially in black and Hispanic populations. Our goal was to quantify use of warfarin therapy, frequency of International Normalized Ratio monitoring, and effectiveness for stroke prophylaxis in Medicare beneficiaries with atrial fibrillation. METHODS: This was a cohort study of Medicare beneficiaries with atrial fibrillation who were hospitalized between March 1998 and April 1999 in all 50 US states. The primary outcome was incident hospitalizations for ischemic stroke based on validated International Classification of Diseases, 9th Revision, Clinical Modification codes. RESULTS: Two thirds of ideal anticoagulation candidates were prescribed warfarin on hospital discharge. In unadjusted analyses, the stroke rates per 100 patient years of warfarin therapy were 5.2 in (non-Hispanic) white Medicare beneficiaries, 10.6 in black beneficiaries, and 12.2 in Hispanic beneficiaries. After adjusting for comorbid conditions, warfarin prescription was more frequent and monitoring more regular in white Medicare beneficiaries than in black or Hispanic beneficiaries (P<0.0001). Warfarin use was associated with 35% fewer ischemic strokes (HR, 0.65; 95% CI, 0.55 to 0.76) compared with no antithrombotic therapy but was less effective in black and Hispanic beneficiaries (P for interaction=0.048). CONCLUSIONS: The use, monitoring, and effectiveness of warfarin therapy are suboptimal in Medicare beneficiaries, especially in black and Hispanic beneficiaries.

Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall.

PURPOSE: Patients at high risk for falls are presumed to be at increased risk for intracranial hemorrhage, and high risk for falls is cited as a contraindication to antithrombotic therapy. Data substantiating this concern are lacking. METHODS: Quality improvement organizations identified 1245 Medicare beneficiaries who were documented in the medical record to be at high risk of falls and 18261 other patients with atrial fibrillation. The patients were elderly (mean 80 years), and 48% were prescribed warfarin at hospital discharge. The primary endpoint was subsequent hospitalization for an intracranial hemorrhage, based on ICD-9 codes. RESULTS: Rates (95% confidence interval [CI]) of intracranial hemorrhage per 100 patient-years were 2.8 (1.9-4.1) in patients at high risk for falls and 1.1 (1.0-1.3) in other patients. Rates (95% CI) of traumatic intracranial hemorrhage were 2.0 (1.3-3.1) in patients at high risk for falls and 0.34 (0.27-0.45) in other patients. Hazard ratios (95% CI) of other independent risk factors for intracranial hemorrhage were 1.4 (1.0-3.1) for neuropsychiatric disease, 2.1 (1.6-2.7) for prior stroke, and 1.9 (1.4-2.4) for prior major bleeding. Warfarin prescription was associated with intracranial hemorrhage mortality but not with intracranial hemorrhage occurrence. Ischemic stroke rates per 100 patient-years were 13.7 in patients at high risk for falls and 6.9 in other patients. Warfarin prescription in patients prone to fall who had atrial fibrillation and multiple additional stroke risk factors appeared to protect against a composite endpoint of stroke, intracranial hemorrhage, myocardial infarction, and death. CONCLUSION: Patients at high risk for falls with atrial fibrillation are at substantially increased risk of intracranial hemorrhage, especially traumatic intracranial hemorrhage. However, because of their high stroke rate, they appear to benefit from anticoagulant therapy if they have multiple stroke risk factors.

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.

Comorbidity indices to predict mortality from Medicare data: results from the national registry of atrial fibrillation.

BACKGROUND: By accounting for level of comorbidity, risk-adjustment models should quantify the risk of death. How accurately comorbidity indices predict risk of death in Medicare beneficiaries with atrial fibrillation is unclear. OBJECTIVES: We sought to quantify how well 3 administrative-data based comorbidity indices (Deyo, Romano, and Elixhauser) predict mortality compared with a chart-review index. DESIGN: We undertook a retrospective cohort study using Medicare claim data (1995-1999) and medical record review. SUBJECTS: We studied Medicare beneficiaries (n = 2728; mean age = 77) with a common cardiac dysrhythmia, atrial fibrillation. MEASURES: The outcome was time to death with the accuracy of the comorbidity indices measured by the c-statistic. RESULTS: Correlation between Deyo and Romano indices was strong, but weak between them and the other indices. Prevalence of many comorbidity conditions varied with different indices. Compared with demographic data alone (c = 0.64), all comorbidity indices predicted death significantly (P < 0.001) better: the c index was 0.76 for Deyo, 0.78 for Romano, 0.76 for Elixhauser, and 0.75 for medical record review. The 95% confidence intervals of the c-statistic for the 4 indices overlapped with one another. Key comorbidity conditions for death included metastatic cancer, neuropsychiatric disease, heart failure, and liver disease. CONCLUSION: The predictive accuracy of 3 administrative-data based indices was similar and comparable with chart-review.

Accuracy of ICD-9-CM codes for identifying cardiovascular and stroke risk factors.

OBJECTIVES: We sought to determine which ICD-9-CM codes in Medicare Part A data identify cardiovascular and stroke risk factors. DESIGN AND PARTICIPANTS: This was a cross-sectional study comparing ICD-9-CM data to structured medical record review from 23,657 Medicare beneficiaries aged 20 to 105 years who had atrial fibrillation. MEASUREMENTS: Quality improvement organizations used standardized abstraction instruments to determine the presence of 9 cardiovascular and stroke risk factors. Using the chart abstractions as the gold standard, we assessed the accuracy of ICD-9-CM codes to identify these risk factors. MAIN RESULTS: ICD-9-CM codes for all risk factors had high specificity (>0.95) and low sensitivity (< or =0.76). The positive predictive values were greater than 0.95 for 5 common, chronic risk factors-coronary artery disease, stroke/transient ischemic attack, heart failure, diabetes, and hypertension. The sixth common risk factor, valvular heart disease, had a positive predictive value of 0.93. For all 6 common risk factors, negative predictive values ranged from 0.52 to 0.91. The rare risk factors-arterial peripheral embolus, intracranial hemorrhage, and deep venous thrombosis-had high negative predictive value (> or =0.98) but moderate positive predictive values (range, 0.54-0.77) in this population. CONCLUSIONS: Using ICD-9-CM codes alone, heart failure, coronary artery disease, diabetes, hypertension, and stroke can be ruled in but not necessarily ruled out. Where feasible, review of additional data (eg, physician notes or imaging studies) should be used to confirm the diagnosis of valvular disease, arterial peripheral embolus, intracranial hemorrhage, and deep venous thrombosis.