Effect of heart failure exacerbations on anticoagulation: a prospective, observational, pilot cohort study.
BACKGROUND
Some studies have suggested that heart failure (HF) is associated with excessive anticoagulation, but definitive data or data showing causation do not exist. Knowledge of risk factors for excessive anticoagulation is critical to manage warfarin therapy safely.


OBJECTIVE
This study characterized the relation between HF-associated hypervolemia and excessive anticoagulation in patients with HF taking chronic warfarin therapy.


METHODS
This was a prospective, observational pilot study conducted in a university-based HF clinic. Patients aged 18 to 85 years with HF and taking warfarin were enrolled and were observed for episodes of hypervolemia. Hypervolemia was determined based on multiple clinical factors, including patient-reported symptoms and physical examination. Anticoagulation was assessed longitudinally per standard of care by measurement of the international normalized ratio (INR). A chi(2) analysis was used to determine whether hypervolemia was associated with an increased risk of excessive anticoagulation. Paired and unpaired t tests were used for ad hoc analyses.


RESULTS
Forty patients with 41 HF episodes who were taking warfarin were enrolled between December 2003 and July 2007. Mean (SD) age was 67.2 (11.1) years and mean weight was 218.5 (62.8) pounds; 29 patients (72.5%) were men and 34 (85.0%) were white. Most had systolic dysfunction (n = 26; 65.0%) and were taking warfarin for atrial fibrillation (n = 33; 82.5%); the mean weekly warfarin dose was 30.8 (17.5) mg. There were 41 evaluable hypervolemia episodes over a mean follow-up of 14.5 (9.0) months. The mean INR change during hypervolemia was -0.02 (0.82) INR unit (P = NS vs baseline). No association was found between hypervolemia episodes and INR increases of > or =50% (P = NS); the results remained nonsignificant for both diastolic and systolic HF when analyzed separately. There was no significant change from baseline INR between patients classified with mild, moderate, or severe hypervolemia or between patients classified according to New York Heart Association (NYHA) functional class (all, P = NS). Patients with NYHA class III had a lower weekly warfarin dose than those with NYHA class II (25.73 vs 31.75 mg; P < 0.01).


CONCLUSIONS
Mild hypervolemia did not appear to be related to excessive anticoagulation in these patients with HF taking chronic warfarin therapy.
Ripley
Toni L
TL
Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma 73126, USA. toni-ripley@ouhsc.edu
Harrison
Donald
D
Germany
Robin E
RE
Adamson
Philip B
PB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy; D001810:Blood Volume; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D019934:International Normalized Ratio; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D000925:Anticoagulants; D014859:Warfarin