A randomised controlled trial of Home medicines reviews following acute coronary syndromes

Coronary heart disease (CHD) is a global healthcare problem. Sometimes fatal for the individual, but always life-changing, and for the wider healthcare system, CHD causes an unprecedented financial burden. CHD commonly presents as an acute coronary syndrome (ACS), which is a prevalent cause of mortality. However, better symptom awareness, a shorter time between symptom onset and acute treatment, and a higher quality of routinely accessible treatments has significantly improved mortality and morbidity in the period soon after ACS. The disease pathway continues after the point of acute treatment and there are multiple behaviours that patients can adopt to prevent further coronary events. This includes lifestyle modification and the use of guideline-recommended medications. There are currently four main classes of medication recommended by consensus-based guidelines following ACS. This includes antiplatelet therapies (aspirin and a `P2Y_12` antagonist), statins, angiotensin-pathway inhibitors, and beta-blockers. The combination of these four medications has been shown to be more effective at reducing the risk of future ACS by comparison to those who stop one or more medications. Many patients struggle with the task of taking these medications as accurately as prescribed (non-adherence) and others stop taking some or all medications (non-persistence). Despite well-established advances in the acute treatment phases of ACS, successful strategies to improve medication adherence and persistence have been lacking. The aim of the current study was to determine if an existing, pharmacist-led home-visit service could be tailored toward the needs of patients following ACS and improve medication adherence and persistence at six months post-discharge. The currently funded Home Medicines Review (HMR) service was utilised. Patients with ACS are eligible for HMR referral, however, to what extent this service is utilised by, or beneficial for patients following ACS is unknown. To tailor the service toward the needs of patients with a recent ACS, accredited pharmacists (APs) who undertake HMRs were invited to participate in an online education package. This included five lectures covering: disease introduction and trial overview; in-hospital management of ACS; lifestyle modifications, cardiac rehabilitation (CR), and chest pain action plans; medication management following ACS; and strategies to improve adherence to therapy. Once viewing all lectures, APs sat a multiple-choice quiz and were required to achieve a 75% pass mark. The education package was peer-reviewed and also underwent a participant evaluation. Successful completion of the education package was a requirement of the trial protocol. The tailored service was termed a directed Home Medicines Review (dHMR). Twenty-seven Tasmanian APs completed the education package, 22 APs (81%) passed the quiz on their first attempt. Twenty-one APs (78%) who successfully completed the education package participated in the trial as described below. A conceptual framework was utilised to design and evaluate a randomised controlled trial of a dHMR delivered at two months post-discharge compared with usual care. The primary outcome was the proportion of patients who were adherent and persistent to a guideline-concordant regimen at six months. This outcome was assessed by a modified medication possession ratio (MMPR). The MMPR was calculated by applying a specialised algorithm to compare the available supply of medication, as obtained through dispensing records, against that required to be fully adherent. Modifications to the algorithm utilised in the current study allowed for determination of adherence and persistence as unique behaviours. Secondary outcomes included mortality, hospital readmissions, length of stays, cardiac rehabilitation completion, smoking cessation, quality of life, survey outcomes, and process outcomes. Data collection was undertaken at hospital discharge, six weeks for baseline surveys, two months for dHMR reports, and follow-up at six months post discharge. Statistical analysis was conducted using SPSS, following standard procedures. The primary outcome was assessed by both univariate chi-square analysis and binary logistic regression to control for potential confounding. Three-hundred and fifty-nine patients with suspected ACS from two Tasmanian public hospitals were screened for enrolment. After exclusion criteria and informed consent, 184 patients were randomised to receive either usual care or a dHMR at two months following hospital discharge. Due to withdrawals and incomplete records a total of 76 control patients and 75 intervention patients were followed to the study endpoint at six months post-discharge. An intention-to-treat analysis was used, however, an on-treatment secondary analysis was also conducted, excluding those who had not followed the trial protocol with regards to timing of the intervention and completion of the education package. There were no significant differences between the study groups for baseline demographics or rates of guideline- concordant prescribing on discharge, which was relatively low at 60.0%. There were only 90 patients who were discharged as guideline-concordant, meanin they could be assessed against the primary outcome. There were no significant differences in the primary outcome with 26 (59.1%) control patients and 22 (47.8%) intervention patients adhering and persisting with guideline-concordant therapy to six months (p=0.284). There was, however, a trend toward a lower proportion of persistence among patients in the intervention group versus the control group at six months (56.5% vs 75.0%, p=0.065). Multivariate analysis supported this finding with an odds ratio for persistence of 3.7 (1.1-12.3, p=0.035) in favour of allocation to the control group. There were no significant changes detected in the secondary outcomes. Similarly, there were few significant changes in the questionnaire results, however, the specific concerns scale of the beliefs about medications questionnaire decreased among intervention patients from six weeks to six months (p=0.034). It was unclear, however, if this decrease occurred as a result of information conveyed that relieved concerns or if medications for which the patient was concerned were stopped, and if so, what degree of impact the intervention had on this action. Analysis of DRPs and review of individual dHMR reports did not clearly support or oppose the finding of lower persistence among intervention patients. Although this analysis did highlight that issues with medication adherence were being identified among some patients, it was interesting to find that other ACS-related problems, not related to adherence, were identified four times as often. This suggested that adherence may not have been given an adequate amount of attention during the dHMR, but also that there may have been improvements in medication management that were not adequately assessed by the primary outcome. Based on assessment of process outcomes, the implementation of the intervention was poor with a large proportion of dHMRs occurring much later than two months post-discharge and over 50% not obtaining GP follow-up. Interestingly this appeared to be somewhat provider specific, suggesting a potential benefit from the use of peer-support and mentorship in future models of research as well as a need to better evaluate the perceptions of the stakeholders involved, such that barriers and enablers to on time completion could be identified. Somewhat similarly, comparisons to other studies suggested that future models of research involving the HMR service may benefit from better integration within the healthcare system and better engagement with the patient. This could be achieved by starting the intervention in hospital and having follow-up sooner after discharge and future research should investigate these options. There were several study limitations. The small sample size limited the confidence in assessing the primary outcome, particularly the assessment of both adherence and persistence. The confidence in assessment of the persistence component, however, was improved by controlling for confounding from a wide variety of baseline variables and this was a positive aspect of the study design. There were also limitations in the collection of complete dispensing records, an inability to assess for improvements in guideline-concordant prescribing, and a lack of quality control over the dHMRs conducted. Each of these factors potentially limits the generalisation of these results to routine practice. This study concluded by finding that the methods used did not adequately tailor the current model of the HMR service to improve adherence or persistence to guideline-recommended medications following ACS. Future research should explore ways of targeting the patients most in need of intervention, utilising highly flexible interventions to suit a wide variety of needs, monitoring for a variety of outcomes that are not solely related to adherence, and providing support for the practitioners involved to deliver the highest quality service possible. Guidance from conceptual frameworks has proved valuable in the design and evaluation of the current study and such an approach could be bolstered with input from all stakeholders involved when designing and evaluating future research of similar interventions.