Oral Warfarin Remains An Effective Treatment Option in the Extended Prophylaxis of VTE for Patients with Cancer: The Effectiveness of the CancerCare Manitoba (CCMB) Anticoagulation Clinic (ACC).

Venothromboembolism (VTE) in patients with active malignancy is associated with adverse outcomes and effective anticoagulation for extended duration with either oral vitamin K antagonist (VKA) or low molecular weight heparin (LMWH) is indicated for as long as the cancer is active. Although current literature suggests that LMWH is more efficacious in reducing VTE recurrence in patients with cancer when compared with oral VKA¹, the need for daily injection and high drug cost are major drawbacks to the upfront use of LMWH in this setting. At our institution in Manitoba (Canada), we treat all patients with first line VKA, managed by a specialized pharmacist-run anticoagulation clinic (CCMB ACC), switching to LMWH if thrombosis recurs despite VKA. The aim of this retrospective review is to access the efficacy and safety of this approach, comparing outcomes between patients with cancer to a convenience cohort (controls) on VKA managed by the same ACC and to that of the literature. We hypothesize that appropriate anticoagulation with an oral VKA can be achieved through ACC and its use as first line therapy for extended VTE prophylaxis in cancer patients is not associated with significant increase in VTE recurrence or major bleeding episodes.

Methods: We analyzed retrospectively all patients receiving oral VKA who were monitored by the CCMB ACC from July 23, 2002 to August 9, 2007, using the ACC database and CCMB electronic charts. Primary outcome is the time spent within the target INR range (%TSTR) which is defined as the proportion of patient-days for which the INR was between 2 and 3, and imputing daily values between INR tests by linear interpolation². We limit this analysis to include only patients with at least 30 days of follow up to ensure adequate time for stabilization of INR. Secondary outcomes include rate of VTE recurrence, rate of major bleeding and rate of switching to LMWH for any reason. Multinomial logistic regression was performed to identify predictors for poor anticoagulation as well as cox regression to identify predictors of recurrence VTE or bleeding complications.

Results: Although the quality of anticoagulation with oral VKA is inferior in patients with VTE and active cancer when compared to control patients (%TSTR 54% versus 64%, p<0.001), the rate of VTE recurrence and bleeding is similar. The TSTR in this cohort compared favourably with those obtained from the literature (%TSTR 54% vs 46% in the CLOT trial³) and the risk of VTE recurrence and bleeding is not excessive (10% and 5.3% respectively). However, patients with cancer are more likely to experience VKA failure (OR 7.22; 95% CI 1.47–35.5) and risk of death (OR 4.48; 95% CI 2.72–7.34) compared to control. No significant predictors were identified for recurrent VTE but those with poor INR control were more likely to suffer from bleeding complications.

Conclusions: Oral VKA remains an effective option for anticoagulation for most patients and LMWH can be reserved for patients with additional risks for VKA failure and those with poor INR control due to increased risk of bleeding.