4. Discussion
This prospective cohort study showed that 251 out of 460 patients (54.6 %) with combined antithrombotic therapy needed at least one intervention from the multidisciplinary ASP to optimize their antithrombotic therapy. The most common interventions were to define and document the maximum duration of the combined therapy (65.5%), to discontinue the combined antithrombotic therapy (19.4%) and to adjust the dosage (8.1%). More patients with TAT required at least one intervention compared to DAT patients. Complications in terms of bleeding, thromboembolism and death were seen in 54 patients (11.7%), 25 patients (5.4%), 20 patients (4.3%), respectively. Bleeding complications were seen more frequently at admission and among patients who already used a combined antithrombotic therapy before admission.
Previous studies have shown that 20% to 52% of patients on combined antithrombotic therapy had inappropriate prescribing which is confirmed with our results. 15-20 Studies have demonstrated that introducing ASP or a structured daily review has led to a significantly higher overall adherence to guidelines among prescribers.11,20 A learning effect develops over time, because the prescriber will be contacted with every intervention. Our results also underlined the complexity of combined antithrombotic therapy and addressed the importance of implementing an ASP. Considering our primary outcome of this research, we showed that a dedicated ASP is able to capture these inappropriateness and intervene effectively during hospitalisation.
The majority of interventions (65.5%) observed in the current study was to define and document the maximum duration of the combined antithrombotic therapy. This intervention prevents prospectively unnecessarily prolonged use of combined anticoagulant therapy. Also, bleeding complications (n=17) at admission among patients already using combined antithrombotic therapy could be lowered when over-use is avoided by proper definition of the required duration of use.
It is noteworthy that we assessed an expired indication for the combined therapy in one of the five interventions (19.1%). We can therefore assume that inappropriate documentation of the maximum duration will eventually lead to an unnecessarily longer use and avoidable bleeding complications. Therefore, this intervention is appealingly simple, yet very important to assure effectiveness and safety of this therapy.
In our subgroup analyses, we observed that patients with TAT frequently needed more interventions compared to DAT (64.9% vs 52.6%). This can be explained due to the fact that the TAT therapy guidelines may be more complex than DAT. For instance, guidelines advice a very short duration of use of triple therapy (2 weeks up to a maximum of one month) due to a high risk of bleeding which does not weigh against its capacity to prevent thromboembolic events. Besides documenting the duration of use of the triple therapy, also maximum duration for the remaining combination of two antithrombotics should be assessed. Again, due to higher bleeding risk outweighing the prevention of thromboembolic complications, it is advised not to use double antithrombotic combination longer than 6 to 12 months. So, two maximum durations of use should be documented in TAT. This is reflected by our results as we saw ASP that interventions to define the maximum duration of use was significantly more required in the TAT group compared to the DAT group (84.4% vs 59.2%). However, the intervention to discontinue antiplatelet therapy or OAC due to the lack of a valid indication was more seen in patients with DAT compared to patients with TAT (22.7% vs 9.1%). This could be explained by the fact that DAT can generally be used for a longer period of time (e.g. 12 months) and documenting the required duration of use is often postponed (e.g. to outpatient clinic) and lost due to time and more transition moments.
Regarding the safety outcomes, we have observed an overall bleeding rate of 11.7% in patients with combined anticoagulation therapy and an overall thromboembolism rate of 1.3%. Compared to previous studies, our bleeding rate is similar (7.3% - 44.4%). 21-23 The overall bleeding rate seems to be highest in the subgroup of patients who were using TAT prior to hospitalisation. Dreijer et al demonstrated that implementing an antithrombotic stewardship could significantly reduce bleeding and thrombotic events in patients with anticoagulant therapy. Although, the study design and ASP in this specific study differed from our ASP. Their study design was a before-and-after intervention study in which their ASP mainly focused on education, medication reviews by pharmacist, patient counselling and implementation of local anticoagulant guidelines. They also showed that implementation of an antithrombotic team was accompanied by a cost reduction of implementing a multidisciplinary ASP that daily evaluates every combined anticoagulant therapy, avoidable complications and hospitalisation may be prevented. Future studies should focus whether an ASP can effectively reduce bleeding complications in patients with combined antithrombotic therapy.