Thrombophilia and Recurrent DVT
Thrombophilia and Recurrent DVT
Abstract & Commentary
By Andrew S. Artz, MD, Division of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationships relevant to this field of study.
Synopsis: Guidelines have suggested patients on warfarin have an international normalized ratio (INR) recall interval not exceeding four weeks. Witt et al reviewed records from the anticoagulation services in a cohort of 6,073 patients. Of these, 2,504 had stable INR values defined as all INR values over a six-month period within the desired range. Independent predictors of stable INR values included age 70 and older, absence of comorbid heart failure and diabetes. Stable patients were significantly less likely to have a target INR of 3.0 or greater or chronic diseases. INR intervals of more than four weeks could be considered for certain patients likely to stay within the INR range.
Source: Witt D, et al. Hylek on behalf of the Warfarin Associated Research Projects and other EndDeavors (WARPED).Outcomes and predictors of very stable INR control during chronic anticoagulation therapy. Blood. 2009;114:952-956.
Warfarin is an effective and inexpensive oral anticoagulation therapy used to prevent both venous and arterial thromboembolism. However, the narrow therapeutic window requires frequent monitoring, typically measured by the international normalized ratio (INR). Stable and long-term control of INR values within the desired range (usually 2.0 to 3.0 or 2.5 to 3.5) optimizes efficacy while minimizing toxicity. For those with stable INR values, the frequency of repeat testing arises as a common clinical and patient concern. One consensus panel suggested repeating the INR every four weeks or less for warfarin therapy.1 Witt et al sought to identify patient characteristics associated with long-term INR control.
This retrospective study evaluated a cohort of patients followed at the Kaiser Permanente Colorado centralized anticoagulation service. The clinic used standardized warfarin dosing algorithms.2 The study population was comprised of 6,073 patients who had an INR measured at least every eight weeks for six months. Stable patients (n = 2,504) were defined as having all INR values within the desired anticoagulation range over the six-month observation period. These were compared to patients with at least a single INR outside the desired range during any six-month observation period (n = 3,569).
Stable patients were more likely to be 70 years or older, have a target INR of 2.5, and receive anticoagulation for atrial fibrillation. Risk factors for not having a stable INR included a target INR of 3.0 or greater, an indication of a heart valve, comorbid diabetes, heart failure, or prior venous thrombosis. In adjusted analysis, significant predictors of stable group status were age older than 70 years (OR = 1.5) and the absence of comorbid diabetes (OR = 1.87), heart failure (OR = 1.4), or concurrent estrogen therapy (OR = 1.3). Stable patients were less likely to have a target INR of 3.0 or greater and less likely to have high chronic disease scores (OR = 0.96; 95% CI, 0.94-0.98).
As expected, stable patients had fewer anticoagulation-related bleeding events (p < .05) and were less likely to require coadministration of heparin or low-molecular-weight heparin (p < .001).
Commentary
Warfarin therapy is extensively used for primary and secondary prevention of venous and arterial thromboembolic events. Although highly effective, the narrow therapeutic index mandates maintaining INR values within the desired range. Repeated testing of the INR may ensure an INR within the target range, but less frequent monitoring could be considered for patients with chronically stable values. In this study, Witt et al evaluated a large cohort of patients followed by a centralized anticoagulation service within Kaiser Permanente. They found that among 6,703 patients, 2,504 (41%) had stable INRs, defined as having all INR values within the therapeutic range over a six-month observation period, with an INR evaluation every eight weeks or less. Independent predictors for being a patient with a stable INR were age 70 and over, absence of comorbid heart disease, or absence of diabetes. A target INR of 3.0 or greater was associated with not having a stable INR. Witt et al also found, as expected, those with stable INR values had lower rates of bleeding events. The major limitation relates to the fact that anticoagulation clinics, in general, are idealized models of INR monitoring. Although the clinics are effective,3 most patients are monitored through their local physician.
The findings and factors for predicting long-term INR stability are perhaps not surprising, except for more stability among older adults. It is possible that the notion that older adults have more medical compliance problems relates specifically to certain illnesses or medications. The reason other factors such as comorbid diabetes or heart failure reduced the chance of having a stable INR are not clear. One could postulate that the presence of multiple medications and/or additional changes in medication might increase the chance of an INR outside of the desired range.
Still, the results have immediate clinical implications. These data support the concept that a group of patients with very stable INR values can be identified and considered for longer intervals between repeat INR measurements than the recommendation of no more than four weeks. In short, for patients with chronically stable INRs over six months, particularly older adults without significant comorbid diseases and targeting an INR of 2.5, less frequent INR monitoring could be a reasonable strategy. It is likely many physicians already tailor the INR monitoring to patient factors and prior INR values.
References
1. Fuster V, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114:e257-e354.
2. Poller L, et al. Multicentre randomised study of computerised anticoagulant dosage. European Concerted Action on Anticoagulation. Lancet. 1998;352:1505-1509.
3. Sullivan PW, et al. The cost effectiveness of anticoagulation management services for patients with atrial fibrillation and at high risk of stroke in the US. Pharmacoeconomics. 2006;24:1021-1033.
Guidelines have suggested patients on warfarin have an international normalized ratio (INR) recall interval not exceeding four weeks.Subscribe Now for Access
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