Rates, determinants and success of implementing deprescribing in people with type 2 diabetes: A scoping review.

BACKGROUND: Individualizing goals for people with type 2 diabetes may result in deintensification of medication, but a comprehensive picture of deprescribing practices is lacking. AIMS: To conduct a scoping review in order to assess the rates, determinants and success of implementing deprescribing of glucose-, blood pressure- or lipid-lowering medications in people with diabetes. METHODS: A systematic search on MEDLINE and Embase between January 2007 and January 2019 was carried out for deprescribing studies among people with diabetes. Outcomes were rates of deprescribing related to participant characteristics, the determinants and success of deprescribing, and its implementation. Critical appraisal was conducted using predefined tools. RESULTS: Fourteen studies were included; eight reported on rates, nine on determinants and six on success and implementation. Bias was high for studies on success of deprescribing. Deprescribing rates ranged from 14% to 27% in older people with low HbA1c levels, and from 16% to 19% in older people with low systolic blood pressure. Rates were not much affected by age, gender, frailty or life expectancy. Rates were higher when a reminder system was used to identify people with hypoglycaemia, which led to less overtreatment and fewer hypoglycaemic events. Most healthcare professionals accepted the concept of deprescribing but differed on when to conduct it. Deprescribing glucose-lowering medications could be successfully conducted in 62% to 75% of participants with small rises in HbA1c . CONCLUSIONS: Deprescribing of glucose-lowering medications seems feasible and acceptable, but was not widely implemented in the covered period. Support systems may enhance deprescribing. More studies on deprescribing blood pressure- and lipid-lowering medications in people with diabetes are needed.

Prescribing patterns, adherence and LDL-cholesterol response of type 2 diabetes patients initiating statin on low-dose versus standard-dose treatment: a descriptive study.

AIMS: The aim of this study was to describe and compare treatment modifications and discontinuation, adherence levels and response to treatment in patients with type 2 diabetes initiating on low-dose vs. standard-dose statin treatment. METHODS: A 2-year follow-up cohort study was performed using data from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database in patients with type 2 diabetes initiating statin treatment between January 2007 and December 2012. First, we determined whether there were differences in treatment modifications and discontinuation after statin initiation between patients starting on a low-dose vs. standard-dose. Second, we looked at differences in adherence and LDL-cholesterol response after 2 years follow-up between these groups. RESULTS: Around 22% of patients initiated statin treatment on a dose lower than recommended. More than half of them remained on a low dose during a 2-year follow-up period, whereas less than 15% received a dose increase. Of the patients initiating on standard-dose, also more than half remained on the same treatment during this period, whereas 8% received a dose decrease without subsequent increase. Over 25% of patients starting on low-dose or standard-dose treatment discontinued treatment, often within the first 180 days after initiation or after a first treatment change. Patients on low-dose treatment had lower adherence levels and were less likely to have adequate LDL-cholesterol response compared with patients on standard-dose after 2 years follow-up. CONCLUSIONS: Current patterns of statin treatment in patients with type 2 diabetes are suboptimal, with discontinuation, inadequate adherence levels and lack of treatment intensification seen in those who had inadequate LDL-cholesterol response after 2 years of follow-up. Patients starting on low-dose had more treatment modifications, discontinuation and adherence problems as compared with those starting on standard-dose treatment, which calls for a closer look at the rationale of starting patients on low-dose statin treatment.

Predictors of response in initial users of metformin and sulphonylurea derivatives: a systematic review.

AIM: To provide an overview of factors predicting metformin and sulphonylurea treatment response. BACKGROUND: A large variability between individuals in treatment response to metformin and sulphonylurea derivatives exists. Understanding which factors determine response to these drugs may pave the way for more individualized therapy. METHODS: We conducted a systematic search in the MEDLINE, Cochrane and EMBASE databases, between 2003 and 2012 for articles assessing demographic and clinical prediction factors of treatment response in initial users of metformin or sulphonylurea. A literature search of articles referenced within the studies identified was also performed. Treatment response was defined as change in HbA1c level, reaching target HbA1c levels or time to treatment change. Studies were assessed on quality, sample size and type of analysis. Results were summarized by tabulating positive, null and negative associations observed for included predictors. RESULTS: A total of 10 articles (six trial reports and four cohort studies) were obtained, including three of sufficient quality. For metformin, baseline HbA1c , older age, lower BMI and shorter disease duration were found to be predictors of better treatment response in at least three studies of sufficient quality. For sulphonylurea derivatives, baseline HbA1c and shorter duration were identified as predictors of better treatment response in at least two studies of sufficient quality. Race, smoking status, lipid levels, blood pressure, kidney function and comorbidities were not significantly associated with treatment response. CONCLUSIONS: Several demographic and clinical factors were identified as possible predictors of response to metformin and sulphonylurea, but the number of studies with sufficient quality was small. Generally, early treatment seems important for achieving better glycaemic outcomes.

[Reducing the use of medication in the elderly; why or why not?] / Medicatie minderen bij ouderen.

Many healthcare providers agree that reduction or stopping of medication, so-called deprescribing, would be good in vulnerable people with polypharmacy. However, deprescribing is not yet widely conducted. Physicians and pharmacists experience barriers, such as lack of evidence and guidance to support this process. There is also a tendency to maintain the status quo when there are no acute problems. Patients do want fewer pills but the proposal to stop certain medication can lead to resistance or confusion. The needs and concerns from a patient's perspective are a good starting point for desprescribing. It is important to set new goals and to prioritize together which medication can be stopped. It is not only relevant to react to existing problems but also to act proactively when the potential benefits no longer outweigh the medication burden or risks. Recently, more guidance and tools to support deprescribing became available in the Netherlands.

Comparison of various measures for assessing medication refill adherence using prescription data.

BACKGROUND: Several measures using prescription data have been developed for estimating medication refill adherence. Few studies have made direct comparisons, and little is known about the accuracy of these measures in patients on a multiple-drug regimen. PURPOSE: To compare different calculation methods using prescription data for assessing refill adherence. METHOD: An observational cohort study among type 2 diabetes patients was conducted. Adherence to oral glucose-lowering, antihypertensive and lipid-lowering medication was assessed for 2004. We calculated medication possession ratios in a flexible period (MPRF), per calendar year (MPRY) and gaps between refills (GAP) at drug class and therapeutic level. Individual review of drug prescription profiles was conducted to validate identified cases of suboptimal refill adherence. Differences in Area Under the Curve (AUC) of ROC-curves were calculated to compare the methods. RESULTS: Of the 3877 patients, 2969 (77%) patients received oral glucose-lowering medication, 2715 (70%) antihypertensives and 1797 (46%) lipid-lowering medication. Using cutoffs for MPR < 80% and GAP > 30 days, overall rates of suboptimal adherence for these drug classes were 32, 35 and 23% respectively. AUC for measures calculated at drug class level (range 0.85-0.90) were significantly larger than those calculated at therapeutic level (0.72-0.90). For oral glucose-regulating medication and antihypertensives, AUCs were largest for the MPRY and GAP measures (0.87-0.88). For lipid-lowering medication, the AUC was largest for the GAP measure (0.90). CONCLUSIONS: Differences between adherence measures were small and favoured calculation on drug class level. For multiple drug use, both MPRY and GAP were good measures for identifying suboptimal refill adherence.

Perceived medication adverse effects and coping strategies reported by chronic heart failure patients.

BACKGROUND: Data on medication adverse effects (AEs) in chronic heart failure (CHF) are primarily based on results from clinical trials. Little is known about AEs perceived by CHF patients in daily practice and how patients deal with these subjective AEs. AIMS: To describe the scope and nature of perceived AEs of CHF patients, their coping strategies and the relationship of perceived AEs to medication, patient characteristics and quality of life. METHODS: This cross-sectional observational study included a sample of 680 patients previously hospitalised for CHF. Perceived AEs and coping strategies were collected by interviews based on a structured questionnaire. Medication and clinical information were collected by chart review. RESULTS: Of the 670 CHF patients completing the questionnaire, 17% reported at least one AE. In total, 186 AEs were reported of which 15% could not be linked to any medication. Nausea (4%), dizziness (4%), itches (3%) and rash (3%) were the most prevalent. The drug associated with the highest AE rate was pravastatin (27%). On average, more than five different drugs could be related to the AEs headache, dizziness and nausea. Patients reporting AEs had a lower general health perception, younger age and were more often using antiarrhythmic drugs. Of patients experiencing AEs, 69% conferred with their doctor, 24% reported having done nothing in reaction and 2% discontinued their medication without discussing it with the doctor. CONCLUSION: Adverse effects are frequently perceived by CHF patients, but they are difficult to recognise and manage in daily practice.

Adherence to standard-dose or low-dose statin treatment and low-density lipoprotein cholesterol response in type 2 diabetes patients.

OBJECTIVE: To determine the association between adherence, dose and low-density lipoprotein (LDL) cholesterol response in patients with type 2 diabetes initiating statin treatment. RESEARCH DESIGN AND METHODS: This cohort study was performed using data for 2007-2012 from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database. The association between adherence to a standard-dose statin and LDL cholesterol response was assessed using linear regression, adjusting for covariates. The effect of low-dose versus standard-dose was assessed in a propensity-score matched cohort. Adherence rates, defined as the proportion of days covered (PDC), were estimated between statin initiation and LDL outcome measurement. MAIN OUTCOME MEASURE: LDL cholesterol level at follow-up. RESULTS: The effect of adherence on LDL cholesterol response, measured in 2160 patients, was dependent on the baseline LDL cholesterol level. For patients with a baseline LDL cholesterol of 3.7 mmol/l and an adherence rate of 80%, a 40% reduction in LDL cholesterol was predicted. In the matched sample of 1144 patients, the treatment dose showed a difference in impact on the outcome for adherence rates higher than 50%. It was estimated that a patient with a baseline LDL cholesterol of 3.7 mmol/l will need an adherence rate of at least 76% on low-dose and 63% on standard-dose treatment to reach the LDL cholesterol target of 2.5 mmol/l. LIMITATIONS: Adherence was measured as the PDC, which is known to overestimate actual adherence. Also, we were not able to adjust for lifestyle factors. CONCLUSIONS: We determined the concurrent effect of treatment adherence and dose on LDL cholesterol outcomes. Given the adherence levels seen in clinical practice, diabetes patients initiating statin treatment are at high risk of not reaching the recommended cholesterol target, especially when they start on a low-dose statin.

Does a cardiovascular event change adherence to statin treatment in patients with type 2 diabetes? A matched cohort design.

OBJECTIVE: To be effective, adherence to statin treatment is essential. We assessed the effect of an apparent first cardiovascular event on statin adherence rates in type 2 diabetes patients. RESEARCH DESIGN AND METHODS: A matched cohort study was conducted among type 2 diabetes patients initiating statin treatment for primary prevention in the Groningen University IADB.nl pharmacy database. Patients who had a drug-treated cardiovascular event (index date) after statin initiation were matched to a reference patient without such an event with similar gender, age at statin initiation, initiation date, follow-up period and adherence level before the event. Adherence rates were measured as percentages of days covered (PDC), and shifts in adherence levels (non-adherent/partially adherent/fully adherent) and rates around the event were evaluated. RESULTS: We could match 375 of the 855 eligible index patients to a reference patient. Index patients had on average a PDC of 81% after the index date; reference patients had a PDC of 71% (p < 0.001) while both had a PDC of 79% before the index date. Index patients were 4.5 times more likely than reference patients to shift from non-adherent to fully adherent (95% CI 1.1-18.8) and 1.8 times more likely to shift from partially adherent to fully adherent (95% CI 1.2-2.6). In the index group, 26% of patients became more adherent after the first cardiovascular event. In contrast, 20% of patients became less adherent. LIMITATIONS: Medication proxies were used, which could have caused misclassification. Furthermore, a substantial group of index patients could not be matched to a reference patient due to small ranges in matching criteria. CONCLUSIONS: The occurrence of a drug-treated cardiovascular event appeared to avert the declining statin adherence rate observed in diabetes patients without such an event. On the other hand, one in five patients became less adherent after the event, indicating that there are still important benefits to achieve.

Improving drug treatment in general practice.

In the international Drug Education Project, an educational program involving auditing and feedback in peer groups to improve the treatment of asthma and urinary tract infections (UTI) was developed and tested in primary care. Individualized feedback was provided and discussed in 24 Dutch peer groups showing doctors their prescribing practices and underlying reasons for treatment. A parallel, randomized controlled design was used to test the effect on competence and actual prescribing; in one study arm doctors received feedback on asthma treatment and in the other on UTI treatment. Especially the messages to treat asthma exacerbations with oral corticosteroids (17% increase) and to prescribe short courses for UTI (decrease duration of 1.8 days) brought about large improvements. Both messages concerned acute situations, and were clear and relatively easy for GPs to implement. GPs will experience more barriers when changing maintenance treatment of an asthma patient, which could explain the more limited success of this part of the educational program: the proportion of patients treated with inhaled corticosteroids increased 5%. A ceiling effect was experienced regarding drug choice for UTI.

Scope and nature of prescribing decisions made by general practitioners.

BACKGROUND: This study describes cognitive processes of doctors who are deciding on the treatment for a patient. This helps to uncover how prescribing decisions could benefit from (computerised) support. METHODS: While thinking aloud, 61 general practitioners made prescribing decisions for five patients with urinary tract infections or stomach complaints. The resulting 305 transcripts were analysed to determine the scope and nature of the decision processes. Differences in the process were related to case or doctor characteristics, and to differences in the quality of prescribing behaviour. RESULTS: The decision processes were not extensive, particularly for patients with a urinary tract infection. The doctors did not actively consider all possible relevant information. Considerations referring to core aspects of the treatment were made in 159 cases (52%) and to contextual aspects in 111 cases (36%). Habitual behaviour, defined as making a treatment decision without any specific contemplation, was observed in 118 cases (40%) and resulted in prescribing first choice as well as second choice drugs. For stomach complaints, second choice drugs were often prescribed after considering other treatments or in view of specific circumstances. Experience of the doctor was not related to the type of decision process. CONCLUSIONS: The processes observed deviate from the decision theoretic norm of thoroughly evaluating all possible options, but these deviations do not always result in suboptimal prescribing. Decision support is useful for bringing pertinent information and first choice treatments to the prescriber's attention. In particular, information about relevant contraindications, interactions, and costs could improve the quality of prescribing.

Comparison of indicators assessing the quality of drug prescribing for asthma.

OBJECTIVE: To compare different indicators for assessing the quality of drug prescribing and establish their agreement in identifying doctors who may not adhere to treatment guidelines. DATA SOURCES/STUDY SETTING: Data from 181 general practitioners (GPs) from The Netherlands. The case of asthma is used as an example because, in this area, different quality indicators exist whose validity is questioned. The study is part of the European Drug Education Project. STUDY DESIGN: Spearman rank correlations were assessed among the GPs' scores on self-report instruments, aggregated prescribing indicators, and individualized prescribing indicators. Kappa values were calculated as agreement measures for identifying low adherence to the guidelines. DATA COLLECTION: Prescribing data from GPs were collected through pharmacies, public health insurance companies, or computerized GP databases. Two self-report instruments were mailed to the GPs. The GPs first received a questionnaire assessing their competence regarding the treatment of asthma patients. Three months later they received a series of 16 written asthma cases asking for their intended treatment for each case. PRINCIPAL FINDINGS: Correlations between scores based on self-report instruments and indicators based on actual prescribing data were mostly nonsignificant and varied between 0 and 0.21. GPs identified as not adhering to the guidelines by the prescribing indicators often had high scores on the self-report instruments. Correlations between 0.20 and 0.55 were observed among indicators based on aggregated prescribing data and those based on individualized data. The agreement for identifying low adherence was small, with kappa values ranging from 0.19 to 0.30. CONCLUSIONS: Indicators based on self-report instruments seem to overestimate guideline adherence. Indicators assessing prescribing quality at an aggregated level give clearly different results, as compared to indicators evaluating prescribing data on an individual patient level. Caution is needed when using such prescribing indicators to identify low adherence to guidelines. Further validation studies using a gold standard comparison are needed to define the best possible indicator.

How physicians choose drugs.

A drug choice model which includes the physician's attitudes, norms and personal experiences with drugs, was tested. One hundred and sixty-nine physicians were asked to estimate the model's components for the treatment of irritable bowel syndrome (IBS) and of renal colic. Given three drugs for both indications, the physicians gave their expectancies about the treatment outcomes, professional acceptability, patient demand and their personal experiences with the drugs. They also stated the value they assign to each of these components when choosing a drug for IBS and for renal colic. The influence of patient demand on the choice of a specific drug appeared to be negligible. The combined effect of the other three elements of the model predicted the stated drug of first choice correctly in 74% (for IBS) and 78% (for renal colic) of the cases, but further analysis showed that only the drug choices for renal colic were as reasoned as the model assumed. Expectancies and values about treatment outcomes determined the drug choice only in part. For choosing a drug for renal colic, the professional environment was more important. Moreover it was found that drug preferences were more related to expectancies about efficacy than to expectancies about side effects for both disorders. The findings can be useful when trying to change prescribing behaviour. Only a limited effect can be expected from the provision of technical drug information. Especially information about costs is unlikely to change prescribing easily, unless values and norms are changed as well. The importance of the professional environment implies that educational programmes in groups might be more effective than individual approaches.

Towards understanding treatment preferences of hospital physicians.

Seventy-two physicians working in a university hospital in The Netherlands were interviewed to clarify their decision-making process when choosing drugs of preference. Each physician was questioned about the treatment choices for either one or two general case descriptions. The physicians considered only a limited set of different treatment options, on an average 1.7-5.0. Further, the physicians expressed their expectancies as regards various treatment alternatives, and the value or weight they attached to the principle aspects of a treatment. An analytical decision model was used as a reference to gain insight into the extent to which the physicians make decisions based on their own subjective expectancies and values. This model assumes that physicians follow a maximizing strategy by choosing the treatment they personally assess as optimal. It was found that a model including only biomedical expectancies and values predicted the preferred treatment correctly in no more than 53% of the cases. Sometimes, biomedical aspects were disregarded that should have been relevant according to the physicians themselves. Adding aspects of the social environment and experiences improved the prediction of the model substantially; 3 out of 4 treatment preferences could be understood by following an analytical maximizing strategy including biomedical aspects and social aspects and experiences. In the remaining cases, the physicians were not able to describe their decision in terms of this maximizing strategy, which points at the use of alternative decision strategies. One alternative decision strategy mentioned by the physicians was a 'follow-the-routine' decision rule.

Variations in general practitioners' views of asthma management in four European countries.

The aim was to identify differences and similarities in views regarding asthma management among general practitioners in four European countries (Germany, Netherlands, Norway and Sweden), and to explore reasons for suboptimal performance. The results are to be used for the development and tailoring of educational interventions. Semistructured interviews with 20 GPs in each country were conducted and analysed using a phenomenographic approach. The domains of (i) general view of asthma, (ii) the doctor-patient relationship in managing asthma, and (iii) overall management of asthma (treatment goals and evaluation of results) were approached during the interviews. There were different ways of experiencing phenomena related to asthma management both within and between the four countries. Three general views on asthma were found where different perspectives were emphasised: a medical, a 'global' (including community health, social and environmental aspects) and a patient's perspective. Within the medical perspective, only a few German doctors emphasised a psychological aetiology of asthma. The views on the doctor-patient relationship described as 'authoritarian', 'teaching' or 'empowering' occurred similarly in all countries. The majority of the doctors showed confidence in the effectiveness of the pharmaceutical treatment of asthma, some doctors were concerned about limitations, but only in Germany a few doctors were explicitly critical of the values of conventional pharmaceutical treatment. The main treatment goals were either conceived as getting the patient symptom-free (Netherlands, Norway, and Germany) or to control the inflammatory process (Sweden). Several German and some Norwegian doctors expressed the view that patients had to accept the disease and learn how to manage it, while a few German doctors aimed at alternative treatments of asthma. The existence of qualitatively different ways of experiencing asthma management, both in and between countries, calls for consideration when trying to implement general evidence-based treatment guidelines. A variation of approaches in continuing medical education for GPs is needed to address such existing beliefs and conceptions that could sometimes be opposed to the content of educational messages.

Clinical relevance of the gap between pre-marketing trials and medical practice: the case of the cardiovascular drugs.

OBJECTIVES/BACKGROUND: The external validity of trial results of new cardiovascular drugs is limited, because the short-term studies are performed with relatively small, highly selected populations. Using qualitative methods, we examined the clinical relevance of under-representation of subgroups of patients, and the underlying arguments. METHODS: Interviews with 47 physicians and pharmacists involved in the pre- or post-marketing evaluation of cardiovascular drugs, addressing the issue in general and for two new drugs, losartan and atorvastatin, in particular. RESULTS: The respondents were generally familiar with the under-representation of elderly patients, female patients, and patients with comorbidity in pre-marketing trials, but less familiar with details of representation in the cases of losartan and atorvastatin. In particular under-representation of patients with comorbidity was considered relevant. Arguments to confirm or refute the relevance referred to trial methodology, applicability of trial results or aspects of patient treatment. Conditional arguments referred to the aim of the trial, population size, therapeutic drug class or the timing of trials prior to or after drug registration. CONCLUSIONS: To optimise the connection between pre-marketing clinical research and practice, trials should focus more on patient groups relevant to medical practice. If such research is not feasible prior to registration, it should be conducted afterwards. Drug information should allow practitioners to determine variations in the relative effects between subpopulations.

Coping with adverse drug events in patients with heart failure: Exploring the role of medication beliefs and perceptions.

This study describes coping strategies that patients with heart failure (HF) use to manage adverse drug events (ADEs). The included coping strategies were social support seeking, information seeking, non-adherence and taking alleviating medication. The role of beliefs about medication and ADE perceptions in explaining these coping strategies was assessed using the Self-Regulation Model. We performed a cross-sectional study including 250 HF patients who experienced an ADE. Patients completed validated questionnaires assessing their coping strategies, ADE perceptions and medication beliefs. Social support (60%) and information seeking (32%) were the most commonly used strategies to cope with ADEs. Non-adherence was reported by 7% of the patients. Multivariate linear regression analysis showed that demographics, clinical factors and medication beliefs explained only a small amount of the variance in coping strategies, whereas ADE perceptions explained a substantial amount of variance. Path analysis showed that patients' perceptions about the timeline, consequences and controllability of ADEs by the health care provider were directly related to their coping behaviour. The effect of patients' medication beliefs on their coping strategies was consistent with mediation through their ADE perceptions. Our results support the value of the Self-Regulation Model in understanding patients' coping behaviour with regard to ADEs.

Cardiometabolic treatment decisions in patients with type 2 diabetes: the role of repeated measurements and medication burden.

PURPOSE: Clinical guidelines for cardiometabolic risk management indicate a simple threshold-based strategy for treatment, but physicians and their patients may be reluctant to modify drug treatment after a single elevated measurement. We determined how repeated measurements of blood pressure, cholesterol and haemoglobin A1c affect general practitioners' decisions to start or intensify medication in patients with type 2 diabetes. We also evaluated whether medication burden altered these decisions. METHODS: We conducted a cohort study in 3029 patients managed by 62 general practitioners (GPs). We assessed the predictive value of the last risk factor measurement, the number of successive measurements above target level and the percentage change between the last two measurements. Medication burden was assessed as the number of drugs concurrently used. Effects on treatment decisions were estimated by multilevel logistic regression analysis, correcting for clustering at GP level. RESULTS: Repeated high levels of diastolic blood pressure increased the likelihood to start antihypertensive medication (OR=2.08, CI 1.37 to 3.17). Repeated high haemoglobin A1c levels affected intensification of oral glucose-lowering medication (OR=1.71, CI 1.44 to 2.03). Modification of lipid-lowering medication was limited, and only affected by the last total cholesterol level. Starting treatment for all three risk factors, as well as intensifying antihypertensive treatment, was more likely in patients already using more drugs for other chronic diseases. CONCLUSIONS: Waiting for the next measurement before deciding to change medication can explain in part the apparent undertreatment for hypertension and hyperglycaemia, but not for hypercholesterolaemia. Medication burden was not a barrier for treatment modification.