Clinical pharmacist interventions to support adherence to thrombopreventive therapy: Two randomised controlled trials

    Research output: ThesisPh.D. thesis


    The three papers in the thesis were based on two randomised controlled trials (RCTs) on in-hospital clinical pharmacist interventions for improvement of adherence to thrombopreventive therapy in two different populations: outpatients with hypertension and patients with acute stroke/transient ischaemic attack (TIA).

    Poor adherence to thrombopreventive therapy is a highly prevalent problem despite the clear benefits of the therapy. Even complex interventions for improving adherence have only shown modest effect. The field of research has therefore moved towards new strategies with more individualised interventions and team-based care, e.g. integrating a clinical pharmacist with particular focus on patients’ drug-related problems. One approach with growing evidence of improving medication adherence is motivational interviewing (MI). So far, no clinical pharmacist intervention using MI has targeted patients with hypertension or stroke in a hospital care setting. Thus, the aim of this thesis was to develop and evaluate in-hospital pharmacist interventions including MI to improve adherence to primary and secondary thrombopreventive therapy.

    The first study was a RCT, which investigated the effectiveness of a multifaceted pharmacist intervention in stroke and TIA patients. In the study, 102 stroke or TIA patients receiving the intervention were compared with 101 patients receiving usual care. The 6-month intervention consisted of a focused medication review with recommendations to physicians, a MI-based patient interview and three follow-up telephone calls. There was no difference in the primary outcome, the composite medication possession ratio (MPR) for antiplatelets, anticoagulants and statins during the year after hospitalisation, as assessed by analysing prescription refill records. At 12 months, the median MPR (IQR) was 0.95 (0.77-1) in the intervention group and 0.91 (0.83-0.99) in the control group, and 28% and 21% of the patients were non-adherent (MPR < 0.80), (risk difference (RD) 7%; 95% CI -5% - 19%). No significant differences were found for the secondary outcomes: adherence and persistence to specific thrombopreventive medications and a combined clinical endpoint of cardiovascular death, stroke or acute myocardial infarction.

    The second RCT included 532 patients with hypertension from three hospital outpatient clinics. The study examined the effectiveness of an intervention very similar to the one in the first study, except that the patient interview was more structured using the Drug Adherence Work-up (DRAW) tool and an adherence questionnaire for identifying potential adherence and lifestyle-related problems. At 12 months, 20.3% of the patients in the intervention group (N=231) were non-adherent (MPR < 0.80) compared with 30.2% in the control group (N=285) (RD  -9.8 (95% CI -17,3;-2.4) and median MPR (IQR) was 0.93 (0.82-0.99) and 0.91 (0.76-0.98), p=0.02. The combined cardiovascular endpoint was reached by 1.3% in the intervention group and 3.1% in the control group (relative risk 0.41 [95% CI, 0.11-1.50]). No significant differences were found for medication persistence, blood pressure or hospital admissions. In conclusion, the intervention led to improvement in medication adherence, which was sustainable for at least 12 months. An important factor that may have contributed to the different results in the two trials is that the stroke patients - compared to the hypertension patients - may have been more motivated for taking their medication as they just experienced a serious event. Another factor is that a secondary prevention clinic was established during the stroke study, which may have improved adherence in both groups thus leaving little room for improvement.

    The objectives of the third study were to evaluate the process outcomes of the intervention in the hypertension study and to determine the agreement between adherence assessed by the questionnaire used in the intervention and adherence assessed by prescription register data. The process evaluation for the 156 patients receiving the intervention showed that the adherence intervention was feasible for identifying and addressing a large range of potential adherence and lifestyle problems. The medication review revealed 56 drug-related problems and the interview 421 problems, 60% medication-related and 40% lifestyle-related. In connection with the interview, 528 actions were taken within eight different categories. MI was a central action which was exercised in nearly all patients (94%). The intervention was well accepted both by the clinical pharmacists and the patients.  Sensitivity and specificity for the two scales of the adherence questionnaire demonstrating the best agreement with prescription-based measures were about 90% and 30%, and the agreement with refill data was fairly low with kappa values below 0.3, suggesting that the questionnaire only has little value for identifying non-adherence.

    The three studies had added valuable and robust evidence about the effect of clinical pharmacist interventions  for improving medication adherence to thrombopreventive therapy. The hypertension study suggests that engaging a clinical pharmacist in team-based care represents a possible strategy to improve adherence to thrombopreventive therapy. To improve the intervention/establish an effect in stroke patients, future studies should focus on patients who may be more likely to benefit from the intervention, e.g. patients at high risk of cardiovascular events or patients recognised with poor medication behaviour. Before routine implementation, further investigations are required to explore whether the intervention can be translated into better clinical outcomes and whether it is cost-effective.  The intervention was feasible, well accepted and adaptable and the intervention elements quite general, which all increase the likeliness of successful broader implementation and potential translation to other outpatient settings and chronic medication users.

    Translated title of the contributionKlinisk farmaceutiske interventioner til støtte for compliance med thromboseforebyggende behandling: To randomiserede kontrollerede undersøgelser
    Original languageEnglish
    Place of PublicationOdense
    Print ISBNs978-87-93192-59-1
    Publication statusPublished - 5. Nov 2015


    • Medication Adherence
    • Pharmacy services, hospital
    • Motivational interviewing
    • thrombopreventive therapy
    • Clinical pharmacy
    • Hypertension
    • Stroke
    • Clinical pharmacist


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