Differential effect of statin use on coagulation markers: an active comparative analysis in the NEO study.

BACKGROUND: Statins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. This study aimed to compare pro-thrombotic activities of different classes of lipid-lowering drugs in an active comparator design and determine whether there is a relation between statin versus fibrate/niacin use and pro-coagulant factor outcomes. METHODS: This is a cross-sectional analysis of participants from the Netherlands Epidemiology of Obesity study using any class of lipid-lowering drugs, including any types of statins, niacin, and fibrates. We performed linear regression analyses to determine fibrinogen, factor (F) VIII, FIX, and FXI activity in statins versus fibrate/niacin users and adjusted for age, sex, tobacco smoking, body mass index (BMI), hypertension, diabetes, and prevalent cardiovascular disease. RESULTS: Among 1043 participants, the mean age was 58.4 ± 5.2 years, 61% were men, and the mean BMI was 31.3 ± 4.5 kg/m2. Clinical characteristics were balanced between statin and fibrate/niacin users. Statin users had lower mean FXI (18.3 IU/dL, 95% confidence interval (CI) 9.4 to 27.3) levels compared to fibrate/niacin users. The level of FVIII (15.8 IU/dL, 95% CI - 0.003 to 31.6), and FIX (11.3 IU/dL, 95% CI - 0.4 to 23.2) were lower in statin users than fibrate/niacin users with marginal statistical significance. CONCLUSION: Current statin use was associated with lower plasma levels of FXI than fibrate/niacin use. The effects on coagulation factors may, in part, explain the benefit of statin therapy rendered in primary and secondary prevention of VTE.

Adherence to direct oral anticoagulant treatment for atrial fibrillation in the Netherlands: A surveillance study.

BACKGROUND: Adherence to direct oral anticoagulants (DOACs) in patients with atrial fibrillation in every day practice may be less than in clinical trials. AIMS: To assess adherence to DOACs in atrial fibrillation patients in every day practice and identify predictors for non-adherence. METHODS: Individual linked dispensing data of atrial fibrillation patients who used DOACs were obtained from the Foundation for Pharmaceutical Statistics covering the Netherlands between 2012 and 2016. One year adherence to DOAC was calculated for initial DOAC as proportion of days covered (PDC) ≥80% and the association between clinical variables and adherence was assessed using logistic regression. In addition, we measured non-persistence, that is, patients who completely stopped their initial DOAC within 1 year follow-up. RESULTS: A total of 4797 apixaban-, 20 454 rivaroxaban- and 18 477 dabigatran users were included. The mean age was 69 years (n = 43 910), which was similar for the DOAC types. The overall proportion of patients with PDC ≥80% was 76%, which was highest for apixaban- (87%), followed by dabigatran- (80%) and rivaroxaban (69%) users. Multivariable analyses revealed that age ≤60 years, no concomitant drug use were predictors for non-adherence. Of atrial fibrillation patients who continued treatment, 97% had a PDC ≥80%, compared with only 56% for those who discontinued their DOAC treatment within 1 year. CONCLUSIONS: Non-adherence to DOACs was associated with age ≤60 years and no concomitant drugs use. Non-adherence was higher in patients who later discontinued DOAC treatment. Results of our study support research into interventions to improve adherence.

Direct oral anticoagulant use and subsequent start of proton pump inhibitors as proxy for gastric complaints.

PURPOSE: Dabigatran use has been linked to gastrointestinal complaints, but it is unknown if this leads to more use of proton pump inhibitors (PPI). Furthermore, it is unknown whether gastrointestinal complaints occur more frequently in dabigatran users compared with other direct oral anticoagulant (DOACs) users. We investigated the association between DOAC use (dabigatran, rivaroxaban, or apixaban) and subsequent PPI initiation as a proxy for gastrointestinal complaints. METHODS: In this population-based observational study with an active-comparator new user study design, anonymised dispensing data from Community Pharmacies in the Netherlands from 2012 to 2016 were used. Patients initiating DOAC for the treatment of atrial fibrillation without any PPI use before or at time of DOAC initiation were included. The outcome measure, subsequent PPI initiation, was determined in 28553 DOAC users. RESULTS: The patients initiating dabigatran (10 942), apixaban (4897), or rivaroxaban (12714) were comparable for age (mean 69 years), sex (62% men), socioeconomic class, and concomitant medication use. The risk of PPI initiation in apixaban versus rivaroxaban users was similar (adjusted hazard ratio 1.06; 95% confidence interval 0.96-1.31) The adjusted hazard ratio of initiating PPI for dabigatran users was 1.21 (95% confidence interval 1.14-1.29) compared with rivaroxaban/apixaban users. The cumulative incidence of PPI initiation at 6 months of follow-up for patients using dabigatran was 13.0%, and 10.0% for those using rivaroxaban/apixaban, yielding a number needing treatment of 33. CONCLUSIONS: Proton pump inhibitor initiation occurred frequently in incident DOAC users but more often in patients treated with dabigatran than in those treated with rivaroxaban or apixaban.

Vitamin supplementation on the risk of venous thrombosis: results from the MEGA case-control study.

BACKGROUND: Whether vitamin supplements decrease venous thrombosis risk is controversial. Previous reports did not all take confounding fully into account, either by randomization or by extensive adjustment. OBJECTIVE: The aim of our study was to determine whether vitamin supplementation decreases the risk of venous thrombosis. DESIGN: A large case-control study included 2506 patients with venous thrombosis, 2506 partner controls, and 2684 random-digit dialing (RDD) controls. When patients were compared with RDD controls, unconditional logistic regression was used to calculate ORs with 95% CIs. When patients were compared with partner controls, conditional logistic regression was used, providing further adjustment for unmeasured confounding. RESULTS: Vitamin use yielded a 37% lower risk of venous thrombosis than no vitamin use (OR: 0.63; 95% CI: 0.57, 0.70) when comparing patients with RDD controls. Adjustment for several putative confounders did not change the estimate (OR: 0.68; 95% CI: 0.61, 0.77). The fully adjusted ORs for vitamin A, vitamin B-6, vitamin B-12, folic acid, vitamin C, vitamin D, vitamin E, and multivitamin use were in the same range. However, when patients were compared with partner controls, ORs attenuated to unity. Results were similar for provoked and unprovoked events, as well as for deep vein thrombosis and pulmonary embolism. CONCLUSIONS: After extensive adjustments, vitamin supplementation was no longer associated with a decreased risk of venous thrombosis in this study. Previous positive results may have been spurious as a result of uncontrolled confounding.