PEER simplified lipid guideline 2023 update: Prevention and management of cardiovascular disease in primary care.

OBJECTIVE: To update the 2015 clinical practice guideline and provide a simplified approach to lipid management in the prevention of cardiovascular disease (CVD) for primary care. METHODS: Following the Institute of Medicine's Clinical Practice Guidelines We Can Trust, a multidisciplinary, pan-Canadian guideline panel was formed. This panel was represented by primary care providers, free from conflicts of interest with industry, and included the patient perspective. A separate scientific evidence team performed evidence reviews on statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors, fibrates, bile acid sequestrants, niacin, and omega-3 supplements (docosahexaenoic acid with eicosapentaenoic acid [EPA] or EPA ethyl ester alone [icosapent]), as well as on 11 supplemental questions. Recommendations were finalized by the guideline panel through use of the Grading of Recommendations Assessment, Development and Evaluation methodology. RECOMMENDATIONS: All recommendations are presented in a patient-centred manner designed with the needs of family physicians and other primary care providers in mind. Many recommendations are similar to those published in 2015. Statins remain first-line therapy for both primary and secondary CVD prevention, and the Mediterranean diet and physical activity are recommended to reduce cardiovascular risk (primary and secondary prevention). The guideline panel recommended against using lipoprotein a, apolipoprotein B, or coronary artery calcium levels when assessing cardiovascular risk, and recommended against targeting specific lipid levels. The team also reviewed new evidence pertaining to omega-3 fatty acids (including EPA ethyl ester [icosapent]) and proprotein convertase subtilisin-kexin type 9 inhibitors, and outlined when to engage in informed shared decision making with patients on interventions to lower cardiovascular risk. CONCLUSION: These updated evidence-based guidelines provide a simplified approach to lipid management for the prevention and management of CVD. These guidelines were created by and for primary health care professionals and their patients.

Lipid-lowering therapies for cardiovascular disease prevention and management in primary care: PEER umbrella systematic review of systematic reviews.

OBJECTIVE: To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins. DATA SOURCES: MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search. STUDY SELECTION: Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events. SYNTHESIS: A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91). CONCLUSION: Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.

Lignes directrices simplifiées de PEER sur les lipides : actualisation 2023: Prévention et prise en charge des maladies cardiovasculaires en soins primaires.

OBJECTIF: Actualiser le guide de pratique clinique de 2015 et présenter une approche simplifiée de la prise en charge des lipides dans la prévention des maladies cardiovasculaires (MCV) en première ligne. MÉTHODES: Conformément aux recommandations de l'Institute of Medicine dans Clinical Practice Guidelines We Can Trust, un panel pancanadien d'experts multidisciplinaires en lignes directrices a été formé. Ce panel était représentatif des cliniciens en soins primaires, libre de tout conflit d'intérêts avec l'industrie, et il tenait compte des points de vue des patients. Une équipe distincte, responsable des données probantes scientifiques, a passé en revue l'information sur les statines, l'ézétimibe, les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9, les fibrates, les chélateurs des acides biliaires, la niacine et les suppléments d'omega-3 (acide docosahexaénoïque avec acide eicosapentaénoïque [EPA] ou ester éthylique de l'EPA seul [icosapent]), ainsi que sur la réponse à 11 questions supplémentaires. Le panel des lignes directrices a finalisé les recommandations en utilisant la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation). RECOMMANDATIONS: Toutes les recommandations sont présentées de manière à être centrées sur le patient et conçues en ayant à l'esprit les besoins des médecins de famille et des autres cliniciens des soins primaires. De nombreuses recommandations sont semblables à celles publiées en 2015. Les statines demeurent le traitement de première intention pour la prévention tant primaire que secondaire des MCV, et le régime méditerranéen et l'activité physique sont recommandés pour réduire le risque cardiovasculaire (en prévention primaire et secondaire). Le panel des lignes directrices a recommandé de ne pas utiliser le dosage des lipoprotéines a, des apolipoprotéines B ou le score calcique coronarien (SCC) dans l'évaluation du risque cardiovasculaire, et de ne pas cibler de seuils précis de taux lipidiques. L'équipe a aussi passé en revue de nouvelles données concernant les acides gras omega-3 (y compris l'ester éthylique d'EAP [icosapent]) et les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9, et a précisé les moments où il convient de procéder à une prise de décision partagée avec les patients sur les interventions pour diminuer le risque cardiovasculaire. CONCLUSION: Ces lignes directrices actualisées et fondées sur des données probantes présentent une approche simplifiée de la prise en charge des lipides pour la prévention et le traitement des MCV. Ce guide de pratique clinique a été conçu par et pour des professionnels de la santé en soins primaires et leurs patients.

Tolerability of bedtime diuretics: a prospective cohort analysis.

OBJECTIVES: We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia. DESIGN: Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration. SETTING: 352 community family practices across 4 Canadian provinces between March 2017 and September 2020. PARTICIPANTS: 552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics. INTERVENTION: Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks. RESULTS: At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p<0.0001; NNH 8.0), and more diuretic users considered nocturia a major burden (15.6% vs 1.3%; difference 14.2%; 95% CI 8.9% to 20.6%; p<0.0001; NNH 7.0). Compared with baseline, diuretic users experienced 1.0 more overnight urinations/week (95% CI 0.0 to 1.75; p=0.01). Results did not differ between sexes. CONCLUSIONS: Switching diuretics to bedtime did promote nocturia, but only 15.6% found nocturia a major burden. At 6 months, 77.3% of diuretic users were adherent to bedtime dosing. Bedtime diuretic use is viable for many hypertensive patients, should it ever become clinically indicated. TRIAL REGISTRATION NUMBER: NCT02990663.

PEER simplified chronic pain guideline: Management of chronic low back, osteoarthritic, and neuropathic pain in primary care.

OBJECTIVE: To develop a clinical practice guideline to support the management of chronic pain, including low back, osteoarthritic, and neuropathic pain in primary care. METHODS: The guideline was developed with an emphasis on best available evidence and shared decision-making principles. Ten health professionals (4 generalist family physicians, 1 pain management-focused family physician, 1 anesthesiologist, 1 physical therapist, 1 pharmacist, 1 nurse practitioner, and 1 psychologist), a patient representative, and a nonvoting pharmacist and guideline methodologist comprised the Guideline Committee. Member selection was based on profession, practice setting, and lack of financial conflicts of interest. The guideline process was iterative in identification of key questions, evidence review, and development of guideline recommendations. Three systematic reviews, including a total of 285 randomized controlled trials, were completed. Randomized controlled trials were included only if they reported a responder analysis (eg, how many patients achieved a 30% or greater reduction in pain). The committee directed an Evidence Team (composed of evidence experts) to address an additional 11 complementary questions. Key recommendations were derived through committee consensus. The guideline and shared decision-making tools underwent extensive review by clinicians and patients before publication. RECOMMENDATIONS: Physical activity is recommended as the foundation for managing osteoarthritis and chronic low back pain; evidence of benefit is unclear for neuropathic pain. Cognitive-behavioural therapy or mindfulness-based stress reduction are also suggested as options for managing chronic pain. Treatments for which there is clear, unclear, or no benefit are outlined for each condition. Treatments for which harms likely outweigh benefits for all or most conditions studied include opioids and cannabinoids. CONCLUSION: This guideline for the management of chronic pain, including osteoarthritis, low back pain, and neuropathic pain, highlights best available evidence including both benefits and harms for a number of treatment interventions. A strong recommendation for exercise as the primary treatment for chronic osteoarthritic and low back pain is made based on demonstrated long-term evidence of benefit. This information is intended to assist with, not dictate, shared decision making with patients.

Lignes directrices simplifiées de PEER sur la douleur chronique: Gestion de la douleur chronique lombaire, arthrosique et neuropathique en première ligne.

OBJECTIF: Formuler des lignes directrices de pratique clinique pour soutenir la prise en charge de la douleur chronique, y compris la douleur lombaire, arthrosique et neuropathique, dans les soins primaires. MÉTHODES: Ces lignes directrices ont été élaborées en mettant l'accent sur les meilleures données probantes disponibles et sur les principes de décision partagée. Dix professionnels de la santé (4 omnipraticiens, 1 médecin de famille spécialisée en gestion de la douleur, 1 anesthésiste, 1 physiothérapeute, 1 pharmacienne, 1 infirmière praticienne et 1 psychologue), 1 représentant des patients, et 1 pharmacienne et spécialiste de la méthodologie des lignes directrices sans droit de vote composaient le comité des lignes directrices. Les membres ont été sélectionnés en fonction de leur profession, de leur milieu de pratique, et de l'absence d'un conflit d'intérêts de nature financière. Les lignes directrices sont le fruit d'un processus itératif incluant la détermination des questions clés, l'examen des données probantes et la formulation des recommandations des lignes directrices. Trois revues systématiques, totalisant 285 études avec répartition aléatoire et contrôlées ont été réalisées. Ces études n'étaient incluses que si elles avaient rapporté une analyse des répondants (p. ex. combien de patients ont obtenu un soulagement d'au moins 30% de la douleur). Le comité a confié à une équipe d'examen des données (composée de spécialistes des données probantes) la tâche de répondre à 11 autres questions complémentaires. Les principales recommandations découlent d'un consensus au sein du comité. Des cliniciens et des patients ont minutieusement examiné les lignes directrices et les outils de décision partagée avant leur publication. RECOMMANDATIONS: L'activité physique est recommandée comme fondement de la gestion de la douleur arthrosique et lombaire chronique; les données probantes étayant un bienfait ne sont pas concluantes dans le cas de la douleur neuropathique. La thérapie cognitivo-comportementale ou la réduction du stress basée sur la pleine conscience sont également suggérées comme des options pour gérer la douleur chronique. Les traitements pour lesquels le bienfait est clair, non concluant ou absent sont décrits sous chaque affection. Les traitements dont les préjudices surpassent probablement les bienfaits pour toutes les affections étudiées, ou la plupart d'entre elles, sont les opioïdes et les cannabinoïdes. CONCLUSION: Ces lignes directrices sur la gestion de la douleur chronique, y compris la douleur arthrosique, lombaire et neuropathique, met en lumière les meilleures données probantes disponibles, y compris les bienfaits et préjudices pour un certain nombre d'interventions thérapeutiques. Une forte recommandation en faveur de l'exercice comme principal traitement de la douleur arthrosique et lombaire chronique repose sur des données probantes ayant démontré un bienfait depuis longtemps. Cette information vise à contribuer au processus de décision partagée avec le patient et non à le dicter.

Bedtime versus morning use of antihypertensives for cardiovascular risk reduction (BedMed): protocol for a prospective, randomised, open-label, blinded end-point pragmatic trial.

INTRODUCTION: Sleep-time blood pressure correlates more strongly with adverse cardiovascular events than does daytime blood pressure. The BedMed trial evaluates whether bedtime antihypertensive administration, as compared with conventional morning use, reduces major adverse cardiovascular events. METHODS AND ANALYSIS: DesignProspective randomised, open-label, blinded end-point trial.ParticipantsHypertensive primary care patients using blood pressure lowering medication and free from glaucoma.SettingCommunity primary care providers in 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario) are mailing invitations to their eligible patients. Social media campaigns (Google, Facebook) are additionally running in the same provinces.InterventionConsenting participants are allocated via central randomisation to bedtime vs morning use of all antihypertensives.Follow-up(1) Telephone or email questionnaire at 1 week, 6 weeks, 6 months and every 6 months thereafter, and (2) accessing linked governmental healthcare databases tracking hospital and community medical services.Primary outcomeComposite of all-cause death, or hospitalisation for myocardial infarction/acute-coronary syndrome, stroke or congestive heart failure.Secondary outcomesEach primary outcome element on its own, all-cause hospitalisation or emergency department visit, long-term care admission, non-vertebral fracture, new glaucoma diagnosis, 18-month cognitive decline from baseline (via Short Blessed Test).Select other outcomesSelf-reported nocturia burden at 6 weeks and 6 months (no, minor or major burden), 1-year self-reported overall health score (EQ-5D-5L), self-reported falls, total cost of care (acute and community over study duration) and mean sleep-time systolic blood pressure after 6 months (via 24-hour monitor in a subset of 302 sequential participants).Primary outcome analysisCox proportional hazards survival analysis.Sample sizeThe trial will continue until a projected 254 primary outcome events have occurred.Current statusEnrolment ongoing (3227 randomised to date). ETHICS AND DISSEMINATION: BedMed has ethics approval from six research ethics review boards and will publish results in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02990663.

Describing deprescribing trials better: an elaboration of the CONSORT statement.

OBJECTIVE: The objective of this study was to identify key features to be addressed in the reporting of deprescribing trials and to elaborate and explain CONSORT items in this regard. STUDY DESIGN AND SETTING: As a first step in a multistage process and based on a systematic review of deprescribing trials, we elaborated variation in design, intervention, and reporting of the included trials of the review. We identified items that were missed or insufficiently described, using the CONSORT and TIDieR checklists. The resulting list of items, which we considered relevant to be reported in deprescribing trials, were discussed in a single-round Delphi exercise and subsequently in a full-day face-to-face meeting with an international panel of 14 experts. We agreed on CONSORT items for further elaboration with regard to design and reporting of deprescribing trials. RESULTS: We identified seven CONSORT items on trial design, participants, intervention, outcomes, flowchart, and harms, where the investigators of deprescribing trials should take into consideration specific aspects, such as whether or not to use placebo or how to inform participants. CONCLUSION: This article presents an elaboration to the CONSORT statement for the reporting of deprescribing trials. It may also support investigators in motivated design choices.

Higher versus lower doses of ACE inhibitors, angiotensin-2 receptor blockers and beta-blockers in heart failure with reduced ejection fraction: Systematic review and meta-analysis.

BACKGROUND: Current heart failure (HF) guidelines recommend titrating angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and beta-blockers (BBs) to target doses used in pivotal placebo-controlled randomized controlled trials (RCTs). Despite a number of RCTs comparing different doses (i.e. higher versus lower doses) of ACEIs, ARBs and BBs, the effects of higher versus lower doses on efficacy and safety remains unclear. For this reason, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of higher versus lower doses of ACEIs, ARBs and BBs in patients with HFrEF. METHODS: We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) via Ovid from inception to April 25th, 2018 and opentrials.net and clinicaltrials.gov for relevant trials that compared different doses of medications in heart failure. We analyzed trials by drug class (ACEIs, ARBs, and BBs) for efficacy outcomes (all-cause mortality, cardiovascular mortality, all-cause hospitalizations, HF hospitalizations, HF worsening). For safety outcomes, we pooled trials within and across drug classes. RESULTS: Our meta-analysis consisted of 14 RCTs. Using GRADE criteria, the quality of evidence for ACEIs and ARBs was assessed as generally moderate for efficacy and high for adverse effects, whereas overall quality for BBs was very low to low. Over ~2-4 years higher versus lower doses of ACEIs, ARBs or BBs did not significantly reduce all-cause mortality [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.87-1.02)], ARBs RR 0.96 (0.87-1.04), BBs RR 0.25 (0.06-1.01)] or all cause hospitalizations [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.86-1.02)], ARBs RR 0.98 (0.93-1.04), BBs RR 0.93 (0.39-2.24)]. However, all point estimates favoured higher doses. Higher doses of ARBs significantly reduced hospitalization for HF [RR 0.89 (0.80-0.99)- 2.8% ARR], and higher doses of ACEIs and ARBs significantly reduced HF worsening [RR 0.85 (0.79-0.92)- 5.1% ARR and 0.91 (0.84-0.99)- 3.2% ARR, respectively] compared to lower doses. None of the differences between higher versus lower doses of BBs were significant; however, precision was low. Higher doses of these medications compared to lower doses increased the risk of discontinuation due to adverse events, hypotension, dizziness, and for ACEIs and ARBs, increased hyperkalemia and elevations in serum creatinine. Absolute increase in harms for adverse effects ranged from ~ 3 to 14%. CONCLUSIONS: Higher doses of ACEIs and ARBs reduce the risk of HF worsening compared to lower doses, and higher doses of ARBs also reduce the risk of HF hospitalization but the evidence is sparse and imprecise. Higher doses increase the chance of adverse effects compared to lower doses. Evidence for BBs is inconclusive. These results support initially always starting at low doses of ACEIs/ARBs and only titrating the dose up if the patient tolerates dose increases.

Representations of the health value of vitamin D supplementation in newspapers: media content analysis.

OBJECTIVE: To examine the nature of media coverage of vitamin D in relation to its role in health and the need for supplements. DESIGN: Media content analysis. SETTING: Print articles from elite newspapers in the UK, the USA and Canada. PARTICIPANTS: 294 print newspaper articles appearing over 5 years (2009-2014). RESULTS: Newspaper coverage of vitamin D generally supported supplementation. The most common framing of vitamin D in print articles was "adequate vitamin D is necessary for good health." Articles also framed vitamin D as difficult to obtain from food supply and framed vitamin D deficiency as a widespread concern. In discussions of supplementation, 80% articles suggested supplementation is or may be necessary for the general population, yet almost none of the articles discussed the potential harms of vitamin D supplementation in any detail. Print articles named 40 different health conditions in relationship to vitamin D. The most commonly cited conditions included bone health, cancer and cardiovascular health. Although print articles referred to a wide range of scholarly research on vitamin D with varying degrees of endorsement for supplementation, a general tone of support for vitamin D supplementation in media coverage persisted. CONCLUSIONS: Newspaper articles conveyed overall support for vitamin D supplementation. News articles linked vitamin D to a wide range of health conditions for which there is no conclusive scientific evidence. Media coverage downplayed the limitations of existing science and overlooked any potential risks associated with supplementation.