Clinical trials with direct oral anticoagulants for stroke prevention in atrial fibrillation: how representative are they for real life patients?

PURPOSE: To identify the proportion of real-life patients with atrial fibrillation (AF) eligible for direct oral anticoagulant (DOAC) therapy, based on the inclusion and exclusion criteria used in the clinical studies and based on the officially approved indications as mentioned in the Summary of Product Characteristics (SmPC). METHODS: Data for this retrospective cross-sectional study was extracted from the UZ Brussel Stroke Registry, containing anonymized data of 2205 patients with a suspected stroke. Characteristics of patients with documented AF were compared with the patient characteristics in clinical trials and the approved indications in the SmPC. RESULTS: Data of 468 patients with AF was analyzed. Based on the selection criteria of the clinical trials, significantly less patients were eligible for treatment with rivaroxaban compared to dabigatran etexilate (39.3 versus 47.6 %; p = 0.010), but not compared to apixaban (45.5 %; p = 0.055). Based on the indications and contraindications in the SmPC, significantly fewer patients were eligible for apixaban compared to dabigatran etexilate and rivaroxaban (62.0 % for apixaban, 72.9 % for dabigatran etexilate, and 75.6 % for rivaroxaban; p < 0.001 and p < 0.001, respectively). Significantly, more patients were eligible for DOAC therapy based on the indications and contraindications in the SmPC compared to the inclusion and exclusion criteria of the clinical trials (72.9 versus 47.6 %; p < 0.001 for dabigatran; 75.6 versus 39.3 %; p < 0.001 for rivaroxaban and 62.0 versus 45.5 %; p < 0.001 for apixaban). CONCLUSION: When taking into account the selection criteria from the pivotal clinical trials with DOACs for stroke prevention in AF, less than half of real-life patients are eligible for therapy with one of the DOACs. However, the indications mentioned in the SmPCs of these drugs are less strict.

Relationship between pre-stroke cardiovascular medication use and stroke severity.

INTRODUCTION: Stroke is a major health problem with important morbidity and mortality. Various risk factors and cardiovascular medication groups are known to have an influence on stroke incidence, but less is known about the relation between medication use and stroke severity. AIM: To determine if relationships exist between the pre-stroke cardiovascular medication use and stroke severity. METHODS: A retrospective study was conducted on a database with anonymized data of 1974 patients with a suspected stroke, admitted to the Universitair Ziekenhuis (UZ) Brussel. Stroke severity was quantified using the National Institute of Health Stroke Scale (NIHSS). Cardiovascular medication groups were first included in a multivariable linear regression model. Second, to obtain clinically interpretable results, all variables that were retained in the final linear regression model were introduced in a cumulative odds ordinal logistic regression model with proportional odds. RESULTS: Angiotensin II receptor blockers (ARBs), statins, and antiarrhythmics were significantly associated with stroke severity at the 10 % α level in a multivariable linear regression model, suggesting a possible effect of these medication groups on stroke severity. Only pre-stroke statin use showed a significant relationship with the NIHSS score in the ordinal logistic regression model with an adjusted odds ratio of 0.740 (95 % CI 0.580-0.944; p = 0.015). CONCLUSION: Pre-stroke use of statins is significantly associated with lower stroke severity. No significant relationship was detected between pre-stroke use of other medication groups and stroke severity, defined by the NIHSS score.

Comparison of two approaches of INR-follow-up and determinants of INR-stability.

INTRODUCTION: Patients with atrial fibrillation (AF) and treated with coumarins need a close follow-up of the international normalized ratio (INR)-values. This can be done by the general practitioner (GP) or by a haematologist in an outpatient hospital clinic. OBJECTIVE: To compare both ways of follow-up and to investigate determinants of stable INR-patterns. METHODS: Cross-sectional single-centre study in patients with AF treated at the UZ Brussel, a university hospital in Brussels. Of the 113 patients included in the study, 71 had their INR followed-up by their GP and 42 similar patients were followed-up by a haematologist. Data of these 113 patients were further analysed to identify possible determinants for stable INR-values. RESULTS: The time in therapeutic range (TTR) did not significantly differ between both groups. However, patients in the GP-group had significantly more INR-values under 2.0 compared to patients from the haematologist-group (P = 0.044), whereas patients in the haematologist-group had significantly more INR-values above 3.0 compared to patients from the GP-group (P = 0.038). Reimbursement costs of both ways of follow-up were comparable, but the out-of-pocket costs for the patient were lower in the GP-group. The time since AF diagnosis was the only significant determinant predicting a higher TTR. CONCLUSION: Both approaches of follow-up seem to lead to the same TTR, yielding no reason to advocate one approach above the other. However, the patient costs were lower when followed-up by the GP.

Pharmacists' role in handling problems with prescriptions for antithrombotic medication in Belgian community pharmacies.

BACKGROUND: Community pharmacists have an important task in the follow-up of patients treated with antithrombotics. When delivering these medicines, pharmacists can encounter drug-related problems (DRPs) with substantial clinical and economic impact. OBJECTIVE: To investigate the amount and type of antithrombotic related DRPs as well as how community pharmacists handled these DRPs. SETTING: Belgian community pharmacies. METHODS: MSc pharmacy students of six Belgian universities collected data about all DRPs encountered by a pharmacist during ten half days of their pharmacy internship. Data were registered about DRPs detected at delivery and in an a posteriori setting, when consulting the medical history of the patient. Classification of the DRP, cause of the DRP, intervention and result of the intervention were registered. MAIN OUTCOME MEASURE: Amount and type of antotrombitocs related DRPs occurring in community pharmacies, as well as how community pharmacists handled these DRPs. RESULTS: 3.1 % of the 15,952 registered DRPs concerned antithrombotics. 79.3 % of these DRPs were detected at delivery and 20.7 % were detected a posteriori. Most antithrombotic-related DRPs concerned problems with the choice of the drug (mainly because of drug-drug interactions) or concerned logistic problems. Almost 80 % of the antithrombotic-related DRPs were followed by an intervention of the pharmacist, mainly at the patient's level, resulting in 90.1 % of these DRPs partially or totally solved. CONCLUSION: Different DRPs with antithrombotic medication occurred in Belgian community pharmacies. About 20 % was detected in an a posteriori setting, showing the benefit of medication review. Many of the encountered DRPs were of technical nature (60.7 %). These DRPs were time-consuming for the pharmacist to resolve and should be prevented. Most of the DRPs could be solved, demonstrating the added value of the community pharmacist as first line healthcare provider.