Use of an electronic decision support tool to reduce polypharmacy in elderly people with chronic diseases: cluster randomised controlled trial.

OBJECTIVE: To evaluate the effects of a computerised decision support tool for comprehensive drug review in elderly people with polypharmacy. DESIGN: Pragmatic, multicentre, cluster randomised controlled trial. SETTING: 359 general practices in Austria, Germany, Italy, and the United Kingdom. PARTICIPANTS: 3904 adults aged 75 years and older using eight or more drugs on a regular basis, recruited by their general practitioner. INTERVENTION: A newly developed electronic decision support tool comprising a comprehensive drug review to support general practitioners in deprescribing potentially inappropriate and non-evidence based drugs. Doctors were randomly allocated to either the electronic decision support tool or to provide treatment as usual. MAIN OUTCOME MEASURES: The primary outcome was the composite of unplanned hospital admission or death by 24 months. The key secondary outcome was reduction in the number of drugs. RESULTS: 3904 adults were enrolled between January and October 2015. 181 practices and 1953 participants were assigned to electronic decision support (intervention group) and 178 practices and 1951 participants to treatment as usual (control group). The primary outcome (composite of unplanned hospital admission or death by 24 months) occurred in 871 (44.6%) participants in the intervention group and 944 (48.4%) in the control group. In an intention-to-treat analysis the odds ratio of the composite outcome was 0.88 (95% confidence interval 0.73 to 1.07; P=0.19, 997 of 1953 v 1055 of 1951). In an analysis restricted to participants attending practice according to protocol, a difference was found favouring the intervention (odds ratio 0.82, 95% confidence interval 0.68 to 0.98; 774 of 1682 v 873 of 1712, P=0.03). By 24 months the number of prescribed drugs had decreased in the intervention group compared with control group (uncontrolled mean change -0.42 v 0.06: adjusted mean difference -0.45, 95% confidence interval -0.63 to -0.26; P<0.001). CONCLUSIONS: In intention-to-treat analysis, a computerised decision support tool for comprehensive drug review of elderly people with polypharmacy showed no conclusive effects on the composite of unplanned hospital admission or death by 24 months. Nonetheless, a reduction in drugs was achieved without detriment to patient outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10137559.

Reduction of inappropriate medication in older populations by electronic decision support (the PRIMA-eDS study): a qualitative study of practical implementation in primary care.

BACKGROUND: Within the EU-funded project PRIMA-eDS (Polypharmacy in chronic diseases: Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support) an electronic decision support tool (the "PRIMA-eDS-tool") was developed for general practitioners (GPs) to reduce inappropriate medication in their older polypharmacy patients. After entering patient data relevant to prescribing in an electronic case report form the physician received a comprehensive medication review (CMR) on his/her screen displaying recommendations regarding missing indications, necessary laboratory tests, evidence-base of current medication, dose adjustments for renal malfunction, potentially harmful drug-drug interactions, contra-indications, and possible adverse drug events. We set out to explore the usage of the PRIMA-eDS tool and the adoption of the recommendations provided by the CMR to optimise the tool and prepare it for its future implementation. METHODS: In a qualitative study carried out in North Rhine-Westphalia, Germany, 21 GPs using the PRIMA-eDS tool within the PRIMA-eDS study were interviewed. Interviews encompassed the GPs' attitudes regarding use of the electronic case report form and the CMR, their response to the recommendations, and the implementation of the tool into daily practice routine. The collected data were analysed applying thematic qualitative text analysis. RESULTS: GPs found the patient data entry into the electronic case report form to be inconvenient and time-consuming. The CMR was conducted often outside practice hours and without the patient present. GPs found that the PRIMA-eDS CMR provided relevant information for and had several positive effects on the caring process. However, they encountered several barriers when wanting to change medication. CONCLUSIONS: It is unlikely that the PRIMA-eDS CMR will be used in the future as it is now as patient data entry is too time-consuming. Several barriers towards deprescribing medications were found which are common in deprescribing studies. Given the positive attitude towards the CMR, a new way of entering patient data into the PRIMA-eDS tool to create the CMR needs to be developed.

Correction to: Effectiveness and safety of vitamin K antagonists and new anticoagulants in the prevention of thromboembolism in atrial fibrillation in older adults - a systematic review of reviews and the development of recommendations to reduce inappropriate prescribing.

CORRECTION: After publication of the original article [1] it was found that author Marc Krause's name had been spelt incorrectly. In the original article it is presented as Mark Krause, rather than Marc Krause. The revised spelling has been included in the author list for this Correction.

A set of systematic reviews to help reduce inappropriate prescribing to older people: study protocol.

BACKGROUND: Multimorbidity and polypharmacy are common in older people. Assessment tools or lists of criteria aimed at supporting prescription decisions for older people exist, but have often been based on expert opinion with insufficient consideration of the evidence available. The present paper describes the methods we are using to systematically review the existing evidence on the efficacy and safety of the most commonly prescribed drugs for older people in the management of their chronic medical conditions and to develop recommendations to reduce inappropriate prescriptions for incorporation into the Comprehensive Medication Review (CMR) tool developed by the PRIMA-eDS European project. METHODS: We selected the 20 most relevant drugs/drug classes in terms of prescription volumes and risk of hospitalisation for older people and the most relevant indications for the most common chronic conditions among older people and a total of 35 distinct drug-indication pairs were chosen. Based on clinical considerations we collapsed some indications together, reducing the 35 pairs to a final total of 22 separate systematic reviews (SR). A common methodology will be used for each individual SR, based on the methodological manuals of the Cochrane collaboration and the PRISMA statement for reporting systematic reviews. Our search strategy will have a staged approach where we initially search for systematic reviews and meta-analyses, but if relevant reviews are not found, then search for individual studies (controlled intervention and observational studies). Our pilot work and initial scoping of the literature suggested that very few, relevant individual trials or existing systematic reviews have researched or reported exclusively on older people. Therefore, sufficient data might not be available to perform meta-analysis but we will provide a narrative synthesis describing characteristics and findings of included studies. The collected evidence will be used to construct recommendations on when not to use or to discontinue a drug, or when to reduce its dose. Recommendations will be developed in team meetings using the GRADE methodology to reflect the strength of the recommendation and the quality of the evidence. Recommendations will be built into the CMR tool. DISCUSSION: This protocol has been prepared for a series of systematic reviews which will provide research-based evidence to develop recommendations to reduce inappropriate polypharmacy in older people as part of the CMR tool of the PRIMA-eDS project.

Effectiveness and patient safety of platelet aggregation inhibitors in the prevention of cardiovascular disease and ischemic stroke in older adults - a systematic review.

BACKGROUND: Platelet aggregation inhibitors (PAI) are among the most frequently prescribed drugs in older people, though evidence about risks and benefits of their use in older adults is scarce. The objectives of this systematic review are firstly to identify the risks and benefits of their use in the prevention and treatment of vascular events in older adults, and secondly to develop recommendations on discontinuing PAI in this population if risks outweigh benefits. METHODS: Staged systematic review consisting of three searches. Searches 1 and 2 identified systematic reviews and meta-analyses. Search 3 included controlled intervention and observational studies from review-articles not included in searches 1 and 2. All articles were assessed by two independent reviewers regarding the type of study, age of participants, type of intervention, and clinically relevant outcomes. After data extraction and quality appraisal we developed recommendations to stop the prescribing of specific drugs in older adults following the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. RESULTS: Overall, 2385 records were screened leading to an inclusion of 35 articles reporting on 22 systematic reviews and meta-analyses, 11 randomised controlled trials, and two observational studies. Mean ages ranged from 57.0 to 84.6 years. Ten studies included a subgroup analysis by age. Overall, based on the evaluated evidence, three recommendations were formulated. First, the use of acetylsalicylic acid (ASA) for primary prevention of cardiovascular disease (CVD) in older people cannot be recommended due to an uncertainty in the risk-benefit ratio (weak recommendation; low quality of evidence). Secondly, the combination of ASA and clopidogrel in patients without specific indications should be avoided (strong recommendation; moderate quality of evidence). Lastly, to improve the effectiveness and reduce the risks of stroke prevention therapy in older people with atrial fibrillation (AF) and a CHA2DS2-VASc score of ≥ 2, the use of ASA for the primary prevention of stroke should be discontinued in preference for the use of oral anticoagulants (weak recommendation; low quality of evidence). CONCLUSIONS: The use of ASA for the primary prevention of CVD and the combination therapy of ASA and clopidogrel for the secondary prevention of vascular events in older people may not be justified. The use of oral anticoagulants instead of ASA in older people with atrial fibrillation may be recommended. Further high quality studies with older adults are needed.

Efficacy and safety of metformin in the management of type 2 diabetes mellitus in older adults: a systematic review for the development of recommendations to reduce potentially inappropriate prescribing.

BACKGROUND: Metformin is usually prescribed as first line therapy for type 2 diabetes mellitus (DM2). However, the benefits and risks of metformin may be different for older people. This systematic review examined the available evidence on the safety and efficacy of metformin in the management of DM2 in older adults. The findings were used to develop recommendations for the electronic decision support tool of the European project PRIMA-eDS. METHODS: The systematic review followed a staged approach, initially searching for systematic reviews and meta-analyses first, and then individual studies when prior searches were inconclusive. The target population was older people (≥65 years old) with DM2. Studies were included if they reported safety or efficacy outcomes with metformin (alone or in combination) for the management of DM2 compared to placebo, usual or no treatment, or other antidiabetics. Using the evidence identified, recommendations were developed using GRADE methodology. RESULTS: Fifteen studies were included (4 intervention and 11 observational studies). In ten studies at least 80% of participants were 65 years or older and 5 studies reported subgroup analyses by age. Comorbidities were reported by 9 studies, cognitive status was reported by 4 studies and functional status by 1 study. In general, metformin showed similar or better safety and efficacy than other specific or non-specific active treatments. However, these findings were mainly based on retrospective observational studies. Four recommendations were developed suggesting to discontinue the use of metformin for the management of DM2 in older adults with risk factors such as age > 80, gastrointestinal complaints during the last year and/or GFR ≤60 ml/min. CONCLUSIONS: On the evidence available, the safety and efficacy profiles of metformin appear to be better, and certainly no worse, than other treatments for the management of DM2 in older adults. However, the quality and quantity of the evidence is low, with scarce data on adverse events such as gastrointestinal complaints or renal failure. Further studies are needed to more reliably assess the benefits and risks of metformin in very old (>80), cognitively and functionally impaired older people.

Thiazides in the management of hypertension in older adults - a systematic review.

BACKGROUND: Thiazides are commonly prescribed to older people for the management of hypertension. The objective of this study was to identify the evidence on the risks and benefits of their use among adults aged ≥65 years and to develop recommendations to reduce potentially inappropriate use. METHODS: Systematic review (SR) of the literature covering six databases. We applied a staged search approach, where each search was undertaken only if the previous one did not yield high quality results. Searches 1 and 2 identified relevant SRs and meta-analyses published up to December 2015 from all databases. Search 3 identified additional individual interventional studies (IS) and observational studies (OS) not identified by the preceding searches. We included all studies evaluating the effect of thiazides on patient-relevant outcomes in the management of hypertension with a sufficient number of participants aged ≥65 years or a subgroup analysis based on age. Two independent reviewers extracted data and carried out quality appraisal. Recommendations were developed using the GRADE methodology. RESULTS: Searches 1 to 3 were performed. We included 34 articles reporting on 12 IS and 4 OS. Mean ages ranged from 59 to 83.8 years. Four studies had performed a subgroup analysis by age. Information on comorbidity, polypharmacy and frailty of the participants was scarce or not available. The IS compared thiazides to placebo or other antihypertensive drugs and evaluated cardiovascular endpoints or all-cause-mortality as primary outcomes. The OS investigated the association between thiazide use and the risk of gout, fractures and adverse effects. Our results suggest that thiazides are efficacious in preventing cardiovascular events for this population group. Low-dose regimens of thiazides may be safer than high-dose (low quality of evidence), and a history of gout may increase the risk of adverse events (low quality of evidence). Three recommendations were developed. CONCLUSIONS: The use of low dose treatment with thiazides for the management of hypertension in adults aged 65 and older seems justified, unless a history of gout is present. The quality of the evidence is low and studies rarely describe characteristics of the participants such as polypharmacy and frailty. Further good quality studies are needed.

Impact of strategies to reduce polypharmacy on clinically relevant endpoints: a systematic review and meta-analysis.

AIM: The aim of the present study was to explore the impact of strategies to reduce polypharmacy on mortality, hospitalization and change in number of drugs. METHODS: Systematic review and meta-analysis: a systematic literature search targeting patients ≥65 years with polypharmacy (≥4 drugs), focusing on patient-relevant outcome measures, was conducted. We included controlled studies aiming to reduce polypharmacy. Two reviewers independently assessed studies for eligibility, extracted data and evaluated study quality. RESULTS: Twenty-five studies, including 10 980 participants, were included, comprising 21 randomized controlled trials and four nonrandomized controlled trials. The majority of the included studies aimed at improving quality or the appropriateness of prescribing by eliminating inappropriate and non-evidence-based drugs. These strategies to reduce polypharmacy had no effect on all-cause mortality (odds ratio 1.02; 95% confidence interval 0.84, 1.23). Only single studies found improvements, in terms of reducing the number of hospital admissions, in favour of the intervention group. At baseline, patients were taking, on average, 7.4 drugs in both the intervention and the control groups. At follow-up, the weighted mean number of drugs was reduced (-0.2) in the intervention group but increased (+0.2) in controls. CONCLUSIONS: There is no convincing evidence that the strategies assessed in the present review are effective in reducing polypharmacy or have an impact on clinically relevant endpoints. Interventions are complex; it is still unclear how best to organize and implement them to achieve a reduction in inappropriate polypharmacy. There is therefore a need to develop more effective strategies to reduce inappropriate polypharmacy and to test them in large, pragmatic randomized controlled trials on effectiveness and feasibility.