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.