Direct oral anticoagulants (DOACs) are increasingly used for treatment and prevention of thromboembolic diseases, used in fixed dose regimens. Although their safety and efficacy profiles are... Show moreDirect oral anticoagulants (DOACs) are increasingly used for treatment and prevention of thromboembolic diseases, used in fixed dose regimens. Although their safety and efficacy profiles are considered optimal, clinical events still occur. Given that anticoagulation treatment is a delicate balance between clotting and bleeding, it is possible that an optimal target spot exists where the effect of anticoagulation achieves both the lowest possible risk of bleeding and thrombosis. Other currently available anticoagulants (ie, vitamin K antagonists and heparins) provide important clues for this. If such a target spot exists, tailored DOAC therapy may further benefit patients. This opinion article summarizes the current available evidence that suggests that such a tailored strategy could work. It also describes research suggestions for conducting studies in patient populations such as patients with extremes of body weight or impaired kidney function to evaluate whether tailored treatment with DOACs could lead to better patient outcomes. Show less
Giustozzi, M.; Agnelli, G.; Toro-Cervera, J. del; Klok, F.A.; Rosovsky, R.P.; Martin, A.C.; ... ; Huisman, M.V. 2020
Background International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE)... Show moreBackground International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE. Methods MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel-Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs). Results Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43-0.91;I-2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83-2.08;I-2, 23%). Conclusion In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH. Show less
Zielinski, G.D.; Rein, N. van; Teichert, M.; Klok, F.A.; Rosendaal, F.R.; Meer, F.J.M. van der; ... ; Lijfering, W.M. 2019
Background In contrast to vitamin K antagonists (VKA), direct oral anticoagulants (DOAC's) are not strictly monitored and dose titrated by anticoagulation clinics in the Netherlands. This may... Show moreBackground In contrast to vitamin K antagonists (VKA), direct oral anticoagulants (DOAC's) are not strictly monitored and dose titrated by anticoagulation clinics in the Netherlands. This may affect drug persistence of atrial fibrillation (AF) patients, whom often require lifelong treatment. Objectives To assess persistence of DOACs and of VKAs in patients with AF. Methods Dispensing data from the Dutch Foundation of Pharmaceutical Statistics were used to monitor persistence of AF patients to DOAC from 1 January 2012-1 April 2016. In addition, we estimated the persistence of AF patients to VKA between 1 January 2004 and 1 January 2012 in data from the Anticoagulation Clinic Leiden. Non-persistence was defined as the cumulative incidence of patients who completely stopped DOAC, switched to another oral anticoagulant or stopped their VKA. Results DOAC users (n = 77 333) were younger than VKA users (n = 10 079; 70 vs 73 years). Non-Persistence to DOAC (ie stopping with any oral anticoagulant) was 34% at 1 and 64% at 4 years, compared to 22% at one and 36% at 4 years for VKA. Approximately a Twenty-five percent of those who had stopped their initial DOAC switched to another anticoagulant (VKA or another DOAC). Multivariable analyses revealed that young age, female sex, no concomitant drug use and non-adherence were predictors for non-persistence of DOAC. Conclusions Persistence to DOAC was low and in line with other observational studies, and higher for VKA. Our results show a clear correlation between age <60 years and worse persistence, as well as with female and non-adherence to DOAC. Show less
Huisman, M.V.; Ferreira, M.; Feuring, M.; Fraessdorf, M.; Klok, F.A. 2018
