Deprescribing antipsychotics for behavioural and psychological symptoms of dementia and insomnia: Evidence-based clinical practice guideline.

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper and stop antipsychotics; to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. METHODS: The overall team comprised 9 clinicians (1 family physician, 1 family physician specializing in long-term care, 1 geriatric psychiatrist, 2 geriatricians, 4 pharmacists) and a methodologist; members disclosed conflicts of interest. For guideline development, a systematic process was used, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence was generated from a Cochrane systematic review of antipsychotic deprescribing trials for the behavioural and psychological symptoms of dementia, and a systematic review was conducted to assess the evidence behind the benefits of using antipsychotics for insomnia. A review of reviews of the harms of continued antipsychotic use was performed, as well as narrative syntheses of patient preferences and resource implications. This evidence and GRADE quality-of-evidence ratings were used to generate recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and stakeholders for review and revisions were made at each stage. RECOMMENDATIONS: We recommend deprescribing antipsychotics for adults with behavioural and psychological symptoms of dementia treated for at least 3 months (symptoms stabilized or no response to an adequate trial) and for adults with primary insomnia treated for any duration or secondary insomnia in which underlying comorbidities are managed. A decision-support algorithm was developed to accompany the guideline. CONCLUSION: Antipsychotics are associated with harms and can be safely tapered. Patients and caregivers might be more amenable to deprescribing if they understand the rationale (potential for harm), are involved in developing the tapering plan, and are offered behavioural advice or management. This guideline provides recommendations for making decisions about when and how to reduce the dose of or stop antipsychotics. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients and families.

Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration.

OBJECTIVE: To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. DATA SOURCES: A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene ( CFH) and age-related maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. DATA SYNTHESIS: Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. CONCLUSIONS: The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.

Assessment of Oral Anticoagulant Use in Residents of Long-Term Care Homes: Evidence for Contemporary Suboptimal Use.

OBJECTIVE: To describe the quality of warfarin use in residents of long-term care facilities and investigate potential predictors oral anticoagulant use. DESIGN: Retrospective chart review (August 2013 to September 2014). SETTING: Thirteen long-term care (LTC) and assisted living facilities (ALF). PARTICIPANTS: Residents from LTC or ALF settings who ( a) received warfarin or direct-acting oral anticoagulants (DOACs) and ( b) residents with a valid indication for oral anticoagulants such as atrial fibrillation, venous thromboembolism, but were not receiving these drugs. PRIMARY OUTCOME: Time in therapeutic international normalized ratio (INR) range (TTR). RESULTS: A total of 563 residents (70% female) with an average age of 85 years were identified. Participants had an average of 7.5 comorbidities and 9 medications. A total of 391 (69%) residents with indications for OACs were receiving such medications. Indications were atrial fibrillation (63%), venous or pulmonary embolism (16%), cardiac valves (0.4%); 26% did not have documented indications. Warfarin and DOACs were prescribed for 213 (38%) and 178 (32%) respectively, and 172 (31%) received no OACs The TTR ranged from 56%-75% (mean 63%). The frequency of INR determinations ranged from every 7 to 20 days, (mean 13 days) with no apparent relationship between frequency of testing and TTR. CONCLUSION: The TTR was higher (63.8%) than literature average (50%), but remains suboptimal given expected benefits of TTRs >75% versus TTRs circa 60%. Documentation of indications for OACs needs improvement, and it is possible that OACs are underused. Further work is necessary to understand how OAC use may be optimized in these facilities.

Deprescribing versus continuation of chronic proton pump inhibitor use in adults.

BACKGROUND: Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures). OBJECTIVES: To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater). SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. MAIN RESULTS: The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. AUTHORS' CONCLUSIONS: In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.

Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline.

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper or stop proton pump inhibitors (PPIs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. METHODS: Five health professionals (1 family physician, 3 pharmacists, and 1 gastroenterologist) and 5 nonvoting members comprised the overall team; members disclosed conflicts of interest. The guideline process included the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, with a detailed evidence review in in-person, telephone, and online meetings. Uniquely, the guideline development process included a systematic review of PPI deprescribing trials and examination of reviews of the harm of continued PPI use. Narrative syntheses of patient preferences and resource-implication literature informed recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and then to health care professional associations for review and revisions made at each stage. A decision-support algorithm was developed in conjunction with the guideline. RECOMMENDATIONS: This guideline recommends deprescribing PPIs (reducing dose, stopping, or using "on-demand" dosing) in adults who have completed a minimum of 4 weeks of PPI treatment for heartburn or mild to moderate gastroesophageal reflux disease or esophagitis, and whose symptoms are resolved. The recommendations do not apply to those who have or have had Barrett esophagus, severe esophagitis grade C or D, or documented history of bleeding gastrointestinal ulcers. CONCLUSION: This guideline provides practical recommendations for making decisions about when and how to reduce the dose of or stop PPIs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Deprescribing antihyperglycemic agents in older persons: Evidence-based clinical practice guideline.

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper, stop, or switch antihyperglycemic agents in older adults. METHODS: We focused on the highest level of evidence available and sought input from primary care professionals in guideline development, review, and endorsement processes. Seven clinicians (2 family physicians, 3 pharmacists, 1 nurse practitioner, and 1 endocrinologist) and a methodologist comprised the overall team; members disclosed conflicts of interest. We used a rigorous process, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, for guideline development. We conducted a systematic review to assess evidence for the benefits and harms of deprescribing antihyperglycemic agents. We performed a review of reviews of the harms of continued antihyperglycemic medication use, and narrative syntheses of patient preferences and resource implications. We used these syntheses and GRADE quality-of-evidence ratings to generate recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and stakeholders for review and revisions were made at each stage. A decision-support algorithm was developed to accompany the guideline. RECOMMENDATIONS: We recommend deprescribing antihyperglycemic medications known to contribute to hypoglycemia in older adults at risk or in situations where antihyperglycemic medications might be causing other adverse effects, and individualizing targets and deprescribing accordingly for those who are frail, have dementia, or have a limited life expectancy. CONCLUSION: This guideline provides practical recommendations for making decisions about deprescribing antihyperglycemic agents. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Improving the legibility of prescription medication labels for older adults and adults with visual impairment.

OBJECTIVES: Most current prescription labels fail to meet print guidelines, especially in print size. We therefore compared the legibility of current prescription medication labels against the legibility of prototype labels, based on current guidelines for legibility. METHOD: Sample medication labels were obtained from pharmacies, and prototype medication labels were developed according to legibility guidelines from nongovernmental organizations and pharmacy organizations. Three groups of participants, consisting of older adults with normal vision, older adults with visual impairment and younger adults with visual impairment (total N = 71) took part. Participants were asked to read and rank the labels. Reading speed and accuracy were determined. RESULTS: Accuracies were high (75%-100%), and there were no significant differences between samples or prototypes or between groups. Prototypes, however, were read faster than samples (p < 0.001). Subjectively, participants preferred the largest print option (p < 0.001) and instructions with the numbers written in highlighted uppercase words (p < 0.001). DISCUSSION: The results indicate that improvements to the label would include larger print size, a consistent layout with left justification and using upper case with highlighting for emphasis of the numbers in the instructions.

An interdisciplinary memory clinic: a novel practice setting for pharmacists in primary care.

Pharmacists have developed innovative practices in various settings as singular providers or as members of multidisciplinary or interdisciplinary teams. Examples include pharmacists practicing in heart failure, hypertension, or hyperlipidemia clinics. There is a paucity of literature describing pharmacists in interdisciplinary memory clinics and specifically pharmacists practicing in interdisciplinary, primary care-based memory clinics. New practice models should be disseminated to guide others in the development of similar models given the complexity of this population. Patients with dementia are more difficult to manage because of cognitive impairment, behavioral and psychological symptoms, the common presence of multiple comorbidities, and related polypharmacy and caregiver issues. These challenges require expertise in neurodegenerative disorders and geriatrics. The purpose of this article is to describe the role of clinical pharmacists providing care to patients with cognitive complaints in a primary care-based, interdisciplinary memory clinic, with a focus on how the pharmacist practices and is integrated in this collaborative care setting. Patients are assessed using an interdisciplinary approach, with team consensus for assessment and planning of care. Pharmacists' activities include assessment of (1) appropriateness of medications based on frailty, (2) medications that can impair cognition and/or function, (3) medication adherence and management skills, and (4) vascular risk factor control. Pharmacists provide education regarding medications and diseases, ensure appropriate transitions in care, and conduct home visits. Pharmacist participation in this clinic represents a novel opportunity to advance pharmacy practice in primary care, interdisciplinary models. Work is ongoing to describe outcomes attributable to pharmacist participation in this clinic.

Psychotropic and cognitive-enhancing medication use and its documentation in contemporary long-term care practice.

BACKGROUND: In long-term care (LTC) settings, use of psychotropic medications to manage behavioral and psychological symptoms of dementia and use of cognitive enhancers are commonplace. It is important that these medications are properly used to ensure resident well-being, and thus, it is paramount to understand use of these medications in contemporary practice to develop appropriate quality improvement initiatives. OBJECTIVE: To characterize psychotropic and cognition-enhancing medication use LTC residents and current trends in documentation. METHODS: Cross-sectional chart review of residents aged >65 years with dementia receiving psychotropic medications and/or cognitive enhancers. RESULTS: From 180 residents, 84 (82% female) met inclusion criteria (average age 86 years). The prevalence of psychotropic medication use was as follows: cognitive enhancers, 71%; antidepressants, 98%; antipsychotics, 61%; sedative hypnotics, 23%. Quetiapine was the most commonly used antipsychotic (48%), followed by risperidone (28%) and olanzapine (15%), all of which were dosed within accepted guidelines. The duration of therapy ranged from 2 to 5 years for antipsychotic medications and 1» to 3 years for antidepressants. Documentation documentation rates were hightest for psychotropics versus cognitive enhancers. There was no documentation of attempts to lower doses or discontinue psychotropic medications or cognitive enhancers. CONCLUSIONS: Many, but not all psychotropics used were acceptable choices. The duration of therapy appears to be excessive for antipsychotic medications. Documentation of ongoing need for medications varied and could be improved on to better assess residents' medication regimens. Further research will inform efforts to enhance the care of these residents.

Use of ultra-low-dose (≤6 mg) doxepin for treatment of insomnia in older people.

BACKGROUND: Insomnia is one of the most frequent complaints encountered in primary care practice, one that results in significant clinical consequences and cost burden to the public health system. It is more common in elderly adults (≥65 years of age), with frequent complaints regarding sleep maintenance and early morning wakening. Current treatment options have limitations. This review was conducted to evaluate the evidence behind ultra-low-dose doxepin in insomnia and to discuss its potential advantages, its place in therapy and its implications in practice in the treatment of older patients. METHODS: A systematic literature search was conducted of MEDLINE via Ovid, PubMed and EMBASE using the MeSH and key terms "doxepin," "sleep initiation and maintenance disorders," "insomnia," and "low dose." Only randomized controlled trials comparing 3 mg and/or 6 mg of doxepin to placebo and involving participants diagnosed with primary insomnia were included. Primary outcomes for this review were objective sleep study parameters. RESULTS: Five studies were identified, 3 of which (n = 571) were conducted in older adults. Doxepin 3 mg and 6 mg significantly reduced waking after sleep onset and increased total sleep time. There was no significant difference between the 2 doses of doxepin. Latency to persistent sleep did not differ significantly compared with placebo for any doses of doxepin. The most frequent adverse events reported were somnolence and headache. Adverse events did not appear to be dose-related, and studies reported the incidence of adverse effects to be comparable to placebo. CONCLUSION: Doxepin 3 mg and 6 mg significantly improved and sustained sleep maintenance and sleep duration into the last third of the night but did not significantly affect sleep onset. Sleep benefits were achieved without next-day residual or discontinuation effects. Doxepin appears to be well suited for managing insomnia in older people.

Helping pharmacists to reduce fall risk in long-term care: A clinical tool to facilitate the medication review process.

BACKGROUND: One-third to one-half of adults older than 65 fall at least once per year. Fall prevention through medication management requires little effort and has consistently been shown to reduce risk of falls. The objective of this study was to further develop and perform preliminary pilot testing of an algorithm designed to assist consultant pharmacists in systematically identifying medications that might be modifiable, in order to reduce the risk of falls in older adults. We hypothesized that algorithm use would increase the number of fall-related medication change recommendations made to physicians. METHODS: Four consultant pharmacists were trained to use the algorithm during their routine medication reviews over a 3-week period. An informal survey was administered at the end of the study period to assess the algorithm. RESULTS: Overall, 51% of residents of long-term facilities had 1 or more recommendations for medication changes related to reducing fall risk (range 0-3 recommendations per resident), with an average 0.675 recommendations made per resident. There were more recommendations for men compared with women and for residents receiving more medications, but the number of recommendations did not correspond with age. All 4 pharmacists agreed that the algorithm was useful and worthwhile. DISCUSSION: The absolute 20% increase in recommendations related to falls supports the study hypothesis. Time was cited as a barrier to using the algorithm, but this should decrease with continued use of this tool. CONCLUSION: This preliminary study furthered the development of and confirmed the possible utility and acceptability of a fall risk-reducing algorithm that may be used in practice.

The legibility of prescription medication labelling in Canada: Moving from pharmacy-centred to patient-centred labels.

INTRODUCTION: The legibility of medication labelling is a concern for all Canadians, because poor or illegible labelling may lead to miscommunication of medication information and poor patient outcomes. There are currently few guidelines and no regulations regarding print standards on medication labels. This study analyzed sample prescription labels from Ontario, Canada, and compared them with print legibility guidelines (both generic and specific to medication labels). METHODS: Cluster sampling was used to randomly select a total of 45 pharmacies in the tri-cities of Kitchener, Waterloo and Cambridge. Pharmacies were asked to supply a regular label with a hypothetical prescription. The print characteristics of patient-critical information were compared against the recommendations for prescription labels by pharmaceutical and health organizations and for print accessibility by nongovernmental organizations. RESULTS: More than 90% of labels followed the guidelines for font style, contrast, print colour and nonglossy paper. However, only 44% of the medication instructions met the minimum guideline of 12-point print size, and none of the drug or patient names met this standard. Only 5% of the labels were judged to make the best use of space, and 51% used left alignment. None of the instructions were in sentence case, as is recommended. DISCUSSION: We found discrepancies between guidelines and current labels in print size, justification, spacing and methods of emphasis. CONCLUSION: Improvements in pharmacy labelling are possible without moving to new technologies or changing the size of labels and would be expected to enhance patient outcomes.

Déprescription des antipsychotiques pour les symptômes comportementaux et psychologiques de la démence et l'insomnie: Guide de pratique clinique fondé sur des données probantes.

OBJECTIF: Élaborer un guide de pratique clinique fondé sur des données probantes pour aider les cliniciens à prendre des décisions quant au moment et à la façon de réduire et de cesser les antipsychotiques en toute sécurité; insister sur les données les plus probantes et solliciter les contributions des professionnels des soins primaires pour l'élaboration, la révision et l'approbation des lignes directrices. MÉTHODOLOGIE: L'équipe comptait 9 cliniciens (1 médecin de famille, 1 médecin de famille spécialisée en soins de longue durée, 1 psychiatre gériatrique, 2 gériatres, 4 pharmaciens) et une spécialiste en méthodologie; les membres ont divulgué leurs conflits d'intérêts. Un processus systématique a été utilisé pour l'élaboration du guide de pratique, y compris le protocole GRADE (Grading of Recommendations Assessment, Development and Evaluation). Les données probantes ont été tirées d'une revue systématique de Cochrane portant sur des études sur la déprescription des antipsychotiques pour les symptômes comportementaux et psychologiques de la démence. Nous avons effectué une revue systématique pour évaluer les données probantes étayant les bienfaits de l'utilisation des antipsychotiques pour traiter l'insomnie. Nous avons examiné les revues portant sur les torts associés à l'utilisation des antipsychotiques sur une base continue, et nous avons fait une synthèse narrative des préférences des patients et des répercussions sur le plan des ressources. Ces données probantes, de même que l'évaluation de la qualité des données selon GRADE, ont été utilisées pour produire les recommandations. L'équipe a peaufiné le contenu du guide de pratique et le libellé des recommandations, et elle a résumé les considérations d'ordre clinique pour répondre aux questions courantes des cliniciens de première ligne. Une ébauche du guide de pratique a été distribuée à des cliniciens et à des intervenants aux fins d'examen. Des révisions ont été apportées au texte à chaque étape. RECOMMANDATIONS: Nous recommandons la déprescription des antipsychotiques chez les adultes ayant des symptômes comportementaux et psychologiques de démence traités depuis au moins 3 mois (symptômes stabilisés ou sans réponse après un essai adéquat) et chez les adultes souffrant d'insomnie primaire, quelle que soit la durée du traitement, ou d'une insomnie secondaire lorsque les comorbidités sous-jacentes sont prises en charge. Un algorithme décisionnel accompagne le guide de pratique clinique. CONCLUSION: Les antipsychotiques sont associés à des préjudices et il est possible de procéder à un sevrage en toute sécurité. Les patients et leurs aidants peuvent être plus réceptifs à la déprescription s'ils comprennent ce qui la justifie (potentiel de préjudices), s'ils participent à l'élaboration du plan de sevrage et si on leur offre des conseils ou une prise en charge quant aux comportements. Le présent guide de pratique clinique offre des recommandations pour décider du moment et de la façon de réduire la dose d'antipsychotiques ou de les cesser complètement. Les recommandations servent à aider à prendre les décisions conjointement avec les patients et leur famille plutôt qu'à les dicter.

Longitudinal Control of Lipid Levels in Patients With Premature Coronary Artery Disease.

Background: Lipid-lowering therapy (LLT) is a central aspect of the treatment of patients with coronary artery disease (CAD), and the benefits of LLT accrue over time. However, there are limited real-world data on longitudinal lipid control in patients with premature CAD. Objectives: The purpose of this study was to assess longitudinal attainment of guideline-recommended lipid goals and outcomes in a contemporary cohort of patients with premature CAD. Methods: We enrolled males younger than 50 years and females younger than 55 years with coronary stenosis of >50% and examined achievement of lipid goals, LLT characteristics, and cardiovascular outcomes (major adverse cardiovascular event [MACE]). Results: Of 476 patients who presented with acute coronary syndrome (ST-elevation myocardial infarction, non-ST-segment elevation myocardial infarction, unstable angina) (68%), stable angina (28%), or other symptoms, 73.2% achieved low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L on at least 1 occasion, but only 27.3% consistently stayed in the target range for 3 years after diagnosis. Although 73.9% of patients received high-intensity LLT at the time of diagnosis, only 43.5% had good adherence over the following 3 years. In multivariable analysis, 1 mmol/L increase in time-weighted average exposure to LDL-C, but not the lowest achieved LDL-C, was associated with a higher risk of MACE, hazard ratio 2.02 (95% CI: 1.48-2.76), when adjusted for sex, age, hypertension, diabetes, and smoking. Conclusions: We found low rates of longitudinal lipid target achievement in patients with premature CAD. Cumulative LDL-C exposure, but not lowest achieved LDL-C, was associated with risk of MACE. This highlights the critical importance of longitudinal control of lipids levels and identifies opportunities to improve LLT and maximize the time-dependent benefits of lipid-lowering.

Patient Eligibility for Established and Novel Guideline-Directed Medical Therapies After Acute Heart Failure Hospitalization.

BACKGROUND: Acute heart failure (AHF) hospitalization presents an opportunity to optimize pharmacotherapy to improve outcomes. OBJECTIVES: This study's aim was to define eligibility for initiation of guideline-directed medical therapy and newer heart failure (HF) agents from recent clinical trials in the AHF population. METHODS: The authors analyzed patients with an AHF admission within the CAN-HF (Canadian Heart Failure) registry between January 2017 and April 2020. Heart failure with reduced ejection fraction (HFrEF) was defined as left ventricular ejection fraction (LVEF) ≤40% and heart failure with preserved ejection fraction (HFpEF) as LVEF >40%. Eligibility was assessed according to the major society guidelines or enrollment criteria from recent landmark clinical trials. RESULTS: A total of 809 patients with documented LVEF were discharged alive from hospital: 455 with HFrEF and 354 with HFpEF; of these patients, 284 had a de novo presentation and 525 had chronic HF. In HFrEF patients, eligibility for therapies was 73.6% for angiotensin receptor-neprilysin inhibitors (ARNIs), 94.9% for beta-blockers, 84.4% for mineralocorticoid receptor antagonists (MRAs), 81.1% for sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 15.6% for ivabradine. Additionally, 25.9% and 30.1% met trial criteria for vericiguat and omecamtiv mecarbil, respectively. Overall, 71.6% of patients with HFrEF (75.5% de novo, 69.5% chronic HF) were eligible for foundational quadruple therapy. In the HFpEF population, 37.6% and 59.9% were eligible for ARNIs and SGLT2 inhibitors based on recent trial criteria, respectively. CONCLUSIONS: The majority of patients admitted with AHF are eligible for foundational quadruple therapy and additional novel medications across a spectrum of HF phenotypes.

Is statin-associated cognitive impairment clinically relevant? A narrative review and clinical recommendations.

OBJECTIVE: To explore the impact of statin use on cognition. DATA SOURCES: A literature search was performed using MEDLINE (1950-November 2011), EMBASE (1980-November 2011), and the Cochrane Library (1960-November 2011) using the search terms "cognition/drug effects," "delirium, dementia, amnestic, cognitive disorders/chemically induced," "memory disorders/chemically induced," "hydroxymethylglutaryl-CoA reductase inhibitors/adverse effects," and "hydroxymethylglutaryl-CoA reductase inhibitors." A bibliographic search on included references was also conducted. STUDY SELECTION AND DATA EXTRACTION: Studies were included for analysis if they were conducted in humans and examined the impact of statin use on cognition as either a primary or secondary endpoint; case reports and case series were also included for analysis. DATA SYNTHESIS: Reports of statin-associated cognitive impairment were found primarily in observational studies (eg, case reports/series). One randomized controlled trial demonstrated that simvastatin impaired some measures of cognition compared to placebo. Conversely, in the majority of randomized controlled trials and observational studies, statins were found to have either a neutral or beneficial effect on cognition. Preliminary data suggest that statins that are less lipophilic (ie, pravastatin and rosuvastatin) may be less likely to contribute to cognitive impairment due to limited penetration across the blood-brain barrier. These drugs would be a logical alternative in cases where cognitive impairment secondary to another statin is suspected. CONCLUSIONS: Despite several reports of statin-associated cognitive impairment, this adverse effect remains a rare occurrence among the totality of the literature. If statin-associated cognitive impairment is suspected, a trial discontinuation can reveal a temporal relationship. Switching from lipophilic to hydrophilic statins may resolve cognitive impairment. The vascular benefits and putative cognitive benefits outweigh the risk of cognitive impairment associated with statin use; therefore, the current evidence does not support changing practice with respect to statin use, given this adverse effect.

Assessing the potential adverse consequences of supplemental calcium on cardiovascular outcomes: should we change our approach to bone health?

OBJECTIVE: To assess cardiovascular risks associated with supplemental calcium use to assist clinicians with evidence-based recommendations for patients who have, or who are at risk for, osteoporosis or osteopenia. DATA SOURCES: Literature was accessed through December 2011 using MEDLINE, Cochrane Library, and International Pharmaceutical Abstracts using the terms calcium compounds and cardiovascular disease. In addition, reference citations from the publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles were evaluated. Randomized controlled trials, observational studies, and meta-analyses were included. DATA SYNTHESIS: While supplemental calcium and vitamin D have been demonstrated to improve bone mineral density and decrease the risk of fractures, there have been recent reports that calcium supplements may increase the risk for cardiovascular events. Nine clinical trials and/or meta-analyses were reviewed; 3 documented increases in cardiovascular risk associated with calcium supplements, and 6 did not. No studies were designed to assess cardiovascular outcomes as primary end points. Balancing the evidence from these analyses with the results of randomized controlled trials assessing the effect of calcium on fracture prevention suggests that the benefits of calcium outweigh the cardiovascular risk. CONCLUSIONS: At this time, there is no cause to change routine practice surrounding supplemental calcium use in patients who have, or are at risk for, osteoporosis or osteopenia.

Déprescription des antihyperglycémiants chez les personnes âgées: Guide de pratique clinique fondé sur les données probantes.

OBJECTIF: Formuler des lignes directrices fondées sur les données probantes afin d'aider les cliniciens à décider du moment et de la façon sécuritaire de réduire la dose des antihyperglycémiants, de mettre fin au traitement ou de passer à un autre agent chez les personnes âgées. MÉTHODES: Nous nous sommes concentrés sur les données les plus probantes disponibles et avons cherché à obtenir les commentaires des professionnels de première ligne durant le processus de rédaction, de révision et d'adoption des lignes directrices. L'équipe était formée de 7 professionnels de la santé (2 médecins de famille, 3 pharmaciens, 1 infirmière praticienne et 1 endocrinologue) et d'une spécialiste de la méthodologie; les membres ont divulgué tout conflit d'intérêts. Nous avons eu recours à un processus rigoureux, y compris l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour formuler les lignes directrices. Nous avons effectué une revue systématique dans le but d'évaluer les données probantes indiquant les bienfaits et les torts liés à la déprescription des antihyperglycémiants. Nous avons révisé les revues des torts liés à la poursuite du traitement antihyperglycémiant, et effectué des synthèses narratives des préférences des patients et des répercussions sur les ressources. Ces synthèses et évaluations de la qualité des données selon l'approche GRADE ont servi à formuler les recommandations. L'équipe a peaufiné le texte sur le contenu et les recommandations des lignes directrices par consensus et a synthétisé les considérations cliniques afin de répondre aux questions courantes des cliniciens de première ligne. Une version préliminaire des lignes directrices a été distribuée aux cliniciens et aux intervenants aux fins d'examen, et des révisions ont été apportées au texte à chaque étape. Un algorithme d'appui décisionnel a été conçu pour accompagner les lignes directrices. RECOMMANDATIONS: Nous recommandons de déprescrire les antihyperglycémiants reconnus pour contribuer à l'hypoglycémie chez les personnes âgées à risque ou dans les situations où les antihyperglycémiants pourraient causer d'autres effets indésirables, et d'individualiser les cibles et de déprescrire en conséquence chez les personnes frêles, atteintes de démence ou dont l'espérance de vie est limitée. CONCLUSION: Les présentes lignes directrices émettent des recommandations pratiques pour décider du moment et de la façon de déprescrire les antihyperglycémiants. Elles visent à contribuer au processus de décision conjointement avec le patient et non à le dicter.

Contemporary concepts in the pharmacotherapy of depression in older people.

Late-life depression is common in older people. Its incidence increases significantly after age 70 to 85, as well as among those living in long-term care facilities. Depression contributes to excess morbidity and complicates management of comorbid conditions in older people. Diagnosis and management of depression often present clinicians with a challenge. Indeed, symptoms of depression in older people may not always be the same as those associated with depression in younger people. Additionally, age-related changes in pharmacokinetics and pharmacodynamics also impact selection, dosing, and monitoring of psychopharmacologic regimens. Optimizing management of depression and providing sound advice to older patients with depression requires knowledge and understanding of many clinical factors. The purpose of this review is to highlight salient issues in late-life depression, with a focus on the pharmacotherapy of depression.

Strategies for Transfer From Methadone to Buprenorphine for Treatment of Opioid Use Disorders and Associated Outcomes: A Systematic Review.

OBJECTIVES: To review the currently available evidence on transfer strategies from methadone to sublingual buprenorphine used in clinical trials and observational studies of medication for opioid use disorder treatment, and to consider whether any strategies yield better clinical outcomes than others. METHODS: Six medical and public health databases were searched for articles and conference abstracts. The Cochrane Central Register of Controlled Trials and the World Health Organization International Clinical Trials Registry Platform were used to identify unpublished trial results. Records were dually screened, and data were extracted and checked independently. Results were summarized qualitatively and, when possible, analyzed quantitatively. RESULTS: Eighteen studies described transfer from methadone to buprenorphine. Transfer protocols were extremely varied. Most studies reported successful rates of transfer, even among studies involving transfer from high methadone doses, although lower pretransfer methadone dose was significantly associated with higher rate of successful transfer. Precipitated withdrawal was not reported frequently. A range of innovative approaches to transfer from methadone to buprenorphine remains untested. CONCLUSIONS: Few studies have used designs that enable comparison of different approaches to transfer patients from methadone to buprenorphine. Most international clinical guidelines provide recommendations consistent with the available evidence. However, clinical guidelines should be perceived as providing "guidance" rather than "protocols," and clinicians and patients need to exercise judgment when attempting transfers.