Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers After Coronary Artery Bypass Graft Surgery: A Population-Based Cohort Study.

BACKGROUND: The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) on major adverse cardiovascular events (MACE) in patients who undergo coronary artery bypass graft surgery is equivocal. This retrospective, population-based cohort study evaluated effect of exposure to an ACEI/ARB on MACE using linked administrative databases that included all cardiac revascularization procedures, hospitalizations, and prescriptions for the population of British Columbia, Canada. METHODS AND RESULTS: All adults who underwent coronary artery bypass graft surgery between 2002 and 2020 were eligible. The primary outcome was time to MACE, defined as a composite of all-cause death, myocardial infarction, and ischemic stroke using Cox proportional hazards models with inverse probability treatment weighting. Included were 15 439 patients and 6191 (40%) were prescribed an ACEI/ARB. Mean age was 66 years, 83% were men, and 16% had heart failure (HF). Median exposure time was 40 months. Over the 5-year follow-up, 1623 MACE occurred. Impact of exposure was different for patients with and without HF (P <0.0001 for interaction). After probability-weighting and adjustment for relevant covariates, exposure to ACEI/ARBs was associated with a lower hazard of MACE in patients with HF at 1 year (hazard ratio, 0.13 [95% CI, 0.09-0.19]) and 5 years (hazard ratio, 0.36 [95% CI, 0.30-0.44]). In patients without HF, ACEI/ARBs had a lower hazard of MACE at 1 year (hazard ratio, 0.35 [95% CI, 0.27-0.46]) and 5 years (hazard ratio, 0.66 [95% CI, 0.58-0.76]). CONCLUSIONS: In this population-based study, ACEI/ARBs were associated with a lower hazard of MACE in a cohort of patients post-coronary artery bypass graft surgery irrespective of HF status.

Development and Application of an Attribute-Based Taxonomy on the Benefits of Oral Anticoagulant Switching in Atrial Fibrillation: A Delphi Study.

INTRODUCTION: Patients with atrial fibrillation (AF) often switch between oral anticoagulants (OACs). It can be hard to know why a patient has switched outside of a clinical setting. Medication attribute comparisons can suggest benefits. Consensus on terms and definitions is required for inferring OAC switch benefits. The objectives of the study were to generate consensus on a taxonomy of the potential benefits of OAC switching in patients with AF and apply the taxonomy to real-world data. METHODS: Nine expert clinicians (seven clinical pharmacists, two cardiologists) with at least 3 years of clinical and research experience in AF participated in a Delphi process. The experts rated and commented on a proposed taxonomy on the potential benefits of OAC switching. After each Delphi round, ratings were analyzed with the RAND Corporation/University of California, Los Angeles (RAND/UCLA) appropriateness method. Median ratings, disagreement index, and comments were used to modify the taxonomy. The resulting taxonomy from the Delphi process was applied to a cohort of patients with AF who switched OACs in a population-based administrative health dataset from 1996 to 2019 in British Columbia, Canada. RESULTS: The taxonomy was finalized in two Delphi rounds, reaching consensus on five switch benefit categories: safety, effectiveness, convenience, economic considerations, and drug interactions. Safety benefit (a switch that could lower the risk of adverse drug events) had three subcategories: major bleeding, intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding. Effectiveness benefit had four subcategories: stroke and systemic embolism (SSE), ischemic stroke, myocardial infarction (MI), and all-cause mortality. Real-world OAC switches revealed that more OAC switches had convenience (72.6%) and drug interaction (63.0%) benefits compared to effectiveness (SSE 22.0%, ischemic stroke 11.1%, MI 3.1%, all-cause mortality 10.1%), safety (major bleeding 24.3%, GI bleeding 10.6%, ICH 48.5%), and economic benefits (12.1%). CONCLUSIONS: The Delphi-based taxonomy identified five criteria for the beneficial effects of OAC switching, aiding in characterizing real-world OAC switching.

Adherence to direct or vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: a long-term observational study.

Our objectives were to measure long-term adherence to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and to identify patient factors associated with adherence. Using linked, population-based administrative data from British Columbia, Canada, an incident cohort of adults prescribed OACs for AF was identified. We calculated the proportion of days covered (PDC) as a time-dependent covariate for each 90-day window from OAC initiation until the end of follow-up. Associations between patient attributes and adherence were assessed using generalized mixed effect linear regression models. 30,264 patients were included. Mean PDC was 0.69 (SD 0.28) over a median follow-up of 6.7 years. 54% of patients were non-adherent (PDC < 0.8). After controlling for confounders, factors positively associated with adherence were number of drug class switches, history of stroke or transient ischemic attack, history of vascular disease, time since initiation, and age. Age > 75 years at initiation, polypharmacy (among VKA users only), and receiving DOAC (vs. VKA) were negatively associated with adherence. PDC decreased over time for VKA users and increased for DOAC users. Over half of AF patients studied were, on average, nonadherent to OAC therapy and missed 32% of their doses. Several patient factors were associated with higher or lower adherence, and adherence to VKA declined during therapy while DOAC adherence increased slightly over time. To min im ize the risk stroke, adherence-supporting interventions are needed for all patients with AF, particularly those aged > 75 years, those with prior stroke or vascular disease, VKA users with polypharmacy, and DOAC recipients.

Prevalence of Acetylsalicylic Acid Use for Primary Prevention of Cardiovascular Disease Amongst Older Adults From 2017-2021: a Retrospective Cross-Sectional Study.

Background: Three landmark trials on the use of acetylsalicylic acid (ASA) for primary prevention of cardiovascular disease (CVD) were published in 2018. Since then, major clinical practice guidelines have been updated with recommendations against the routine use of ASA for primary CVD prevention, particularly in older adults. However, little is known about the uptake of this evidence into real world practice. The purpose of this study was to assess the change in ASA usage for primary prevention of CVD in older adults between 2017 and 2021. Methods: A retrospective cross-sectional study of ASA use for primary prevention in ambulatory older adults without known CVD in an urban Canadian city was conducted. Results: Seven hundred and fifty-six participants were included. The mean age was 78.9 years (standard deviation 7.9) and 64.8% were female. One hundred and thirty (17.2%) participants used ASA for primary prevention, including 20.3% in 2017, 17.0% in 2018, 21.8% in 2019, 16.3% in 2020, and 11.0% in 2021 (p = .061). Female sex was associated with lower ASA use (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.68) and hypertension was associated with higher ASA use (OR 2.72, 95% CI 1.73-4.29). Conclusions: Use of ASA for primary CVD prevention in older Canadians decreased between 2017 and 2021, suggesting an uptake of clinical trial data and practice guideline recommendations. Focusing on deprescribing of ASA for primary CVD prevention continues to be warranted, given the risks associated with ASA in this population.

Antithrombotic therapy in patients after transcatheter aortic valve implantation: a network meta-analysis.

AIMS: The optimal antithrombotic therapy to balance the risk of thrombosis and bleeding in patients who undergo transcatheter aortic valve implantation (TAVI) is unknown. This systematic review/network meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of different oral anticoagulant and antiplatelet regimens in patients post-TAVI. METHODS AND RESULTS: MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to April 2023. Co-primary outcomes were all-cause death and major bleeding. We conducted Bayesian network meta-analyses to compare all interventions simultaneously. For each outcome, we generated odds ratios (ORs) with 95% credible intervals using a random-effects model with informative priors, and ranked interventions based on mean surface under the cumulative ranking curve. We included 11 RCTs (n = 6415), including one unpublished RCT. Three trials enrolled patients with an indication for an oral anticoagulant (OAC). Overall risk of bias was low or with some concerns. Median age was 81 years. Median follow-up was 6 months. The Combination of OAC plus single antiplatelet therapy (SAPT) increased the risk of all-cause death compared with dual antiplatelet therapy (DAPT) (OR 1.78, 95% credible interval 1.15-2.77). No other comparisons for all-cause death were significantly different. For major bleeding, SAPT reduced the risk compared with DAPT, direct-acting OAC, and OAC + SAPT (OR 0.20-0.40), and DAPT reduced the risk compared with OAC + SAPT. SAPT and DAPT ranked best for all-cause death, while SAPT ranked best for major bleeding. CONCLUSION: In post-TAVI patients, SAPT may provide the optimal balance of reducing thrombotic events while minimizing the risk of bleeding.

Patients' Beliefs About Their Cardiovascular Medications After Acute Coronary Syndrome: A Prospective Observational Study.

Background: Adherence to secondary preventive pharmacotherapy after an acute coronary syndrome (ACS) is generally poor and is associated with recurrent cardiovascular events. Patients' beliefs about their medications are a strong predictor of intentional nonadherence. Methods: This prospective, observational study assessed adult patients' beliefs about their post-ACS medications, using the Beliefs About Medicines Questionnaire (BMQ), and adherence, using the Medication Adherence Report Scale (MARS-5) at St. Paul's Hospital in Vancouver, Canada during May-December, 2022. The BMQ and MARS-5 were administered in-hospital and at 4 weeks after discharge. Outcomes included difference in BMQ necessity-concerns differential (BMQ-NCD) from hospitalization to 4-week follow-up and factors associated with the BMQ-NCD. Results: Forty-seven participants completed the 4-week follow-up. The mean age was 64 years, and 83% were male. Most presented with a non-ST-segment-elevation ACS. No difference occurred in BMQ-NCD (7.3 vs 6.6, P = 0.29) or MARS-5 scores from discharge to 4 weeks (22.8 vs 23.7, P = 0.06); however, the BMQ specific-necessity subscale score decreased significantly (20.3 vs 18.8, P = 0.002). South Asian and Middle Eastern ethnic origins, compared to European, were associated with a higher BMQ-NCD. Part-time employment and male sex were associated with a lower BMQ-NCD. Conclusions: Participants held favourable beliefs about their post-ACS medications, which were largely unchanged from hospitalization to 4 weeks postdischarge, except for beliefs about the necessity of taking their medications. Those of European descent, those with part-time employment, and males had the lowest BMQ-NCD. Self-reported adherence was high. Ongoing reassessment of patients' beliefs about the necessity of taking their post-ACS medications may be warranted to mitigate further decline in BMQ-NCD.

Contexte: L'adhésion à une pharmacothérapie préventive secondaire après la survenue d'un syndrome coronarien aigu (SCA) est généralement faible et associée à des manifestations cardiovasculaires récurrentes. Les croyances du patient au sujet de ses médicaments représentent un facteur prédictif majeur de la non-adhésion intentionnelle. Méthodologie: Cette étude observationnelle prospective avait pour objectif d'évaluer les croyances des patients au sujet des médicaments à prendre après la survenue d'un SCA, au moyen du questionnaire BMQ (Beliefs About Medicines), ainsi que l'adhésion thérapeutique, à l'aide de l'échelle de rapport sur l'adhésion aux médicaments MARS-5 (Medication Adherence Report Scale), à l'hôpital St. Paul de Vancouver, au Canada, de mai à décembre 2022. Les questionnaires BMQ et MARS-5 ont été administrés pendant l'hospitalisation, puis 4 semaines après le congé de l'hôpital. Les résultats comprenaient la différence du score BMQ-NCD (necessity-concerns differential ­ écart nécessité-inquiétudes), entre l'hospitalisation et le suivi à 4 semaines, et les facteurs associés au score BMQ-NCD. Résultats: Au total, 47 participants ont terminé l'étude, jusqu'au suivi à 4 semaines. L'âge moyen était de 64 ans, et 83 % des sujets étaient de sexe masculin. La plupart des sujets présentaient un SCA sans élévation du segment ST. Aucune variation du score BMQ-NCD (7,3 vs 6,6; p = 0,29) ou MARS-5 (22,8 vs 23,7; p = 0,06) n'a été observée entre le congé de l'hôpital et le suivi à 4 semaines; cependant, le score BMQ spécifique à la nécessité avait significativement diminué (20,3 vs 18.8; p = 0,002). Les origines ethniques sud-asiatiques et moyen-orientales étaient associées à des scores BMQ-NCD plus élevés que les origines européennes. L'occupation d'un emploi à temps partiel et le sexe masculin étaient associés à des scores BMQ-NCD inférieurs. Conclusions: Les participants entretenaient des croyances favorables envers leurs médicaments à prendre après la survenue d'un SCA, qui sont demeurées largement les mêmes entre l'hospitalisation et le suivi, 4 semaines après le congé de l'hôpital, à l'exception des croyances au sujet de la nécessité de prendre les médicaments. Les sujets d'origine européenne, ceux occupant un emploi à temps partiel et les sujets masculins ont eu les scores BMQ-NCD les plus faibles. L'adhésion thérapeutique autosignalée était élevée. Des réévaluations constantes des croyances des patients au sujet de la nécessité de prendre leurs médicaments après la survenue d'un SCA pourraient être justifiées afin d'éviter que les scores BMQ-NCD diminuent davantage.

Retrospective Cross-sectional Analysis of Older Adults Living with Frailty and Anticoagulant Use for Atrial Fibrillation.

Background: Oral anticoagulation (OAC) is recommended for most individuals with atrial fibrillation (AF), including those who are frail. Based on previous literature, those who are frail may be less likely to be prescribed OAC, and up to one-third may receive an inappropriate dose if prescribed a direct oral anticoagulant (DOAC). The objectives of this study were to determine the proportion of frail ambulatory older adults with AF who are prescribed OAC, compare the rates of OAC use across the frailty spectrum, assess the appropriateness of DOAC dosing, and identify if frailty and geriatric syndromes impact OAC prescribing patterns. Methods: Retrospective cross-sectional review of individuals with AF referred to an ambulatory clinic for older adults living with frailty and/or geriatric syndromes. Rockwood clinical frailty score of ≥4 was used to define frailty and DOAC appropriateness was assessed based on the Canadian Cardiovascular Society AF guidelines. Results: Two hundred and ten participants were included. The mean age was 84 years, 49% were female and the median frailty score was 5. Of the 185 participants who were frail, 82% were prescribed an OAC (83% with frailty score of 4, 85% with a frailty score of 5, and 78% with a frailty score of 6). Of those prescribed a DOAC, 70% received a guideline-approved dose. Conclusions: Over 80% of ambulatory older adults with frailty and AF were prescribed an OAC. However, of those prescribed a DOAC, 30% received an unapproved dose, suggesting more emphasis should be placed on initial and ongoing dosage selection.

Use of Guideline-Directed Medical Therapy in Patients Aged 80 Years or Older With Heart Failure With Reduced Ejection Fraction.

Background: Guideline-directed medical therapy (GDMT) reduces morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). Use of GDMT is recommended in all adults with HFrEF, but it is potentially underutilized in patients with advanced age. This study sought to characterize use of GDMT in octogenarians and nonagenarians with HFrEF and identify barriers to initiation and uptitration. Methods: This retrospective cohort study included patients aged 80-99 years at 3 heart failure clinics in the Lower Mainland region of British Columbia, Canada. Patients with a left ventricular ejection fraction ≤ 40% and heart failure hospitalization < 12 months were included. Data were collected between September 2019 and August 2021, for up to 24 months from the initial clinic visit. Results: A total of 91 patients were included. The mean age was 85 years, and the mean left ventricular ejection fraction was 30%. About 50% of patients had New York Heart Association class II symptoms. Throughout the study follow-up period, approximately 91% of patients were on a beta-blocker, 72% were on a renin-angiotensin system (RAS) inhibitor, 31% were on a mineralocorticoid receptor antagonist (MRA), and 4% were on a sodium-glucose cotransporter 2 (SGLT2) inhibitor. The target dose was achieved in 19% of patients on a beta-blocker, 7% on an RAS inhibitor, 11% on an MRA, and 100% on an SGLT2 inhibitor. Frequent barriers to GDMT initiation and/or uptitration were renal dysfunction, hypotension, and hyperkalemia. Conclusions: The levels of use of RAS inhibitors and beta-blockers in patients aged 80-99 years with HFrEF were reasonable, whereas the levels of use of MRAs and SGLT2 inhibitors were low. Achievement of target doses of GDMT was rare, owing to common adverse effects.

Contexte: Le traitement médical recommandé dans les lignes directrices réduit la morbidité et la mortalité chez les patients atteints d'insuffisance cardiaque à fraction d'éjection réduite (ICFER). Ce traitement est préconisé chez tous les adultes atteints d'ICFER, mais pourrait être sous-employé chez les patients d'âge avancé. Cette étude visait à caractériser son utilisation chez les octogénaires et les nonagénaires atteints d'ICFER et à repérer les obstacles à l'initiation d'un tel traitement et à l'augmentation de la dose. Méthodologie: Cette étude de cohorte rétrospective regroupait des patients âgés de 80 à 99 ans de trois cliniques traitant l'insuffisance cardiaque dans la région du Lower Mainland, en Colombie-Britannique, au Canada. Des patients présentant une fraction d'éjection ventriculaire gauche (FEVG) ≤40 % et hospitalisés en raison d'une insuffisance cardiaque dans les 12 derniers mois ont été inclus dans l'étude. Les données ont été recueillies entre septembre 2019 et août 2021, jusqu'à 24 mois après la visite initiale à la clinique. Résultats: Au total, 91 patients ont été inclus dans l'étude. Leur âge moyen était de 85 ans, et la FEVG moyenne, de 30 %. Environ 50 % des patients présentaient des symptômes de la classe II de la New York Heart Association. Pendant toute la période de suivi de l'étude, environ 91 % des patients étaient traités par un bêtabloquant, 72 % par un inhibiteur du système rénine-angiotensine (SRA), 31 % par un antagoniste des récepteurs minéralocorticoïdes (ARM) et 4 % par un inhibiteur du cotransporteur du glucose-sodium de type 2 (SGLT2). La dose cible a été atteinte chez 19 % des patients traités par un bêtabloquant, 7 % de ceux traités par un inhibiteur du SRA, 11 % de ceux recevant un ARM et 100 % des sujets recevant un inhibiteur du SGLT2. Les obstacles fréquents à l'instauration du traitement médical recommandé dans les lignes directrices ou à l'augmentation de la dose étaient la dysfonction rénale, l'hypotension et l'hyperkaliémie. Conclusions: Les taux d'utilisation des inhibiteurs du SRA et des bêtabloquants chez les patients âgés de 80 à 99 ans présentant une ICFER étaient raisonnables, tandis que les taux d'utilisation des ARM et des inhibiteurs du SGLT2 étaient faibles. L'atteinte des doses cibles préconisées dans le traitement médical recommandé dans les lignes directrices était rare en raison des effets secondaires courants.

Decisional Needs and Patient Treatment Preferences for Heart Failure Medications: A Scoping Review.

Background: Pharmacologic management of heart failure with reduced ejection fraction (HFrEF) involves several medications. Decision aids informed by patient decisional needs and treatment preferences could assist in making HFrEF medication choices; however, these are largely unknown. Methods: We searched MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), without language restriction, for qualitative, quantitative, and mixed-method studies that included patients with HFrEF or clinicians providing HFrEF care, and reported data on decisional needs or treatment preferences applicable to HFrEF medications. We classified decisional needs using a modified version of the Ottawa Decision Support Framework (ODSF). Results: From 3996 records, we included 16 reports describing 13 studies (n = 854). No study explicitly assessed ODSF decisional needs; however, 11 studies reported ODSF-classifiable data. Patients commonly reported having inadequate knowledge or information, and difficult decisional roles. No study systematically assessed treatment preferences, but 6 studies reported on attribute preferences. Reducing mortality and improving symptoms frequently were ranked as being important, whereas cost importance rankings varied, and adverse events generally were ranked as being less important. Conclusion: This scoping review identified key decisional needs regarding HFrEF medications, notably inadequate knowledge or information, and difficult decisional roles, which can readily be addressed by decision aids. Future studies should systematically explore the full scope of ODSF-based decisional needs in patients with HFrEF, along with relative preferences among treatment attributes to further inform development of individualized decision aids.

Contexte: La prise en charge pharmacologique de l'insuffisance cardiaque avec fraction d'éjection réduite (ICFER) peut être réalisée à l'aide de plusieurs médicaments. Des outils d'aide à la décision reposant sur les besoins décisionnels et les préférences thérapeutiques des patients pourraient faciliter le choix des médicaments dans les cas d'ICFER. Malheureusement, ce type d'outils demeure largement inconnu. Méthodologie: Nous avons interrogé les bases de données MEDLINE, Embase et Cumulative Index to Nursing and Allied Health Literature (CINAHL), sans restriction quant à la langue, pour trouver des études qualitatives, quantitatives et mixtes incluant des patients atteints d'ICFER ou des cliniciens prodiguant des soins aux personnes atteintes d'ICFER. Nous avons recueilli les données sur les besoins décisionnels ou les préférences thérapeutiques qui s'appliquaient aux médicaments contre l'ICFER, puis avons classé les besoins décisionnels à l'aide d'une version modifiée du Modèle d'aide à la décision d'Ottawa (MADO). Résultats: Sur un total de 3996 résultats, nous avons retenu 16 rapports décrivant 13 études (n = 854). Aucune étude n'évaluait explicitement les besoins décisionnels selon le MADO, mais 11 études faisaient état de données qu'il était possible de classer selon ce modèle. Les patients ont fréquemment mentionné avoir des connaissances ou des informations inadéquates et un rôle décisionnel difficile. Aucune étude n'évaluait systématiquement les préférences de traitement, mais six études ont rapporté des préférences quant aux attributs du traitement. La réduction de la mortalité et l'atténuation des symptômes étaient souvent classées comme importantes, les coûts faisaient l'objet d'un classement variable et les événements indésirables étaient généralement classés comme étant peu importants. Conclusion: Cette revue exploratoire a permis de relever des besoins décisionnels clés concernant les médicaments contre l'ICFER, notamment des connaissances et des informations inadéquates, et un rôle décisionnel difficile, besoins qui peuvent facilement être comblés par des outils d'aide à la décision. De futures études devraient explorer de manière systématique la portée complète des besoins décisionnels des patients atteints d'ICFER selon le MADO, ainsi que les préférences relatives quant aux attributs du traitement pour orienter l'élaboration d'outils personnalisés d'aide à la décision.

Using Red Panel Traps to Detect Spotted-Wing Drosophila and its Infestation in US Berry and Cherry Crops.

Spotted-wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), is an invasive pest of thin-skinned fruits in the United States. Monitoring traps are an integral part of SWD integrated pest management, allowing early detection and timely management of this pest. An ideal monitoring trap should be easy to use, effective in capturing SWD, sensitive and selective to male SWD which are easy to identify due to their spotted wings, and able to predict fruit infestation from trap captures. Deli-cup-based liquid traps (grower standard), which make in-situ observations difficult, were compared with red-panel sticky traps, both baited with commercial lures (Scentry, Trécé Broad-Spectrum (BS), and Trécé High-Specificity (HS)), across several US states in blueberries (lowbush and highbush), blackberry, raspberry, and cherry crops during 2018 and 2021. Results showed that red-panel traps effectively captured SWD, were able to detect male SWD early in the season while also being selective to male SWD all season-long, and in some cases linearly related male SWD trap captures with fruit infestation. Scentry and Trécé BS lures captured similar numbers of SWD, though Trécé BS and Trécé HS were more selective for male SWD in red panel traps than liquid traps in some cases. In conclusion, due to its ease of use with less processing time, red-panel traps are promising tools for detecting and identifying male SWD in-situ and for predicting fruit infestation. However, further research is needed to refine the trap captures and fruit infestation relationship and elucidate the trap-lure interactions in berry and cherry crops.

Managing Heart Failure With Reduced Ejection Fraction in Patients With Chronic Kidney Disease: A Case-Based Approach and Contemporary Review.

Patients with heart failure with reduced ejection fraction (HFrEF) often have concurrent chronic kidney disease (CKD), which can make initiating and titrating the 4 standard pharmacologic therapies a challenge. Drug dosing is often based on a calculation of the patient's creatine clearance or estimated glomerular filtration rate (eGFR), but it should also incorporate the trend in their renal function over time and the risk of toxicity of the drug. The presence of CKD in a patient should not preclude the use of a renin-angiotensin system inhibitor, although patients should be monitored frequently for worsening renal function and hyperkalemia. Sacubitril/valsartan is not recommended in patients with an eGFR < 30 mL/min per 1.73 m2. Of the 3 ß-blockers recommended in the management of HFrEF, only bisoprolol may accumulate in patients with renal impairment; however, patients should still be titrated to the target dose (10 mg daily) or the maximally tolerated dose, depending on their clinical response. The sodium-glucose cotransporter 2 inhibitors are effective at reducing adverse cardiovascular and renal outcomes in patients with HFrEF and CKD (eGFR ≥ 25 mL/min per 1.73 m2 with dapagliflozin or ≥ 20 mL/min per 1.73 m2 with empagliflozin), although declining kidney function is a risk, due to the osmotic diuretic effect. Finally, mineralocorticoid receptor antagonist therapy should be considered in all patients with HFrEF and an eGFR ≥ 30 mL/min per 1.73 m2. The starting dose should be low (eg, 6.25-12.5 mg daily or 12.5 mg every other day) and can be uptitrated based on the patient's renal function and serum potassium.

Les patients atteints d'insuffisance cardiaque avec fraction d'éjection réduite (ICFER) présentent souvent une néphropathie chronique (NC) concomitante, ce qui peut compliquer l'instauration et l'ajustement du traitement par les quatre types de médicaments principaux. La posologie repose souvent sur le calcul de la clairance de la créatine ou du débit de filtration glomérulaire estimé (DFGe), mais l'évolution de la fonction rénale du patient et le risque de toxicité du médicament devraient également être pris en compte. Une NC chez un patient ne devrait pas empêcher l'utilisation d'un inhibiteur du système rénine-angiotensine, mais il convient alors d'effectuer un suivi fréquent de ces patients pour détecter un éventuel déclin de la fonction rénale ou une hyperkaliémie. L'association sacubitril-valsartan n'est pas recommandée chez les patients ayant un DFGe < 30 ml/min/1,73 m2. Parmi les trois ß-bloqueurs recommandés pour la prise en charge de l'ICFER, seul le bisoprolol pourrait se bioaccumuler chez les patients souffrant d'une dysfonction rénale; il convient toutefois d'ajuster progressivement la posologie jusqu'à l'atteinte de la dose cible (10 mg par jour) ou de la dose maximale tolérée, selon la réponse clinique. Les inhibiteurs du cotransporteur sodium-glucose de type 2 permettent de réduire l'incidence des manifestations cliniques cardiovasculaires et rénales indésirables chez les patients atteints d'ICFER et de NC (DFGe ≥ 25 ml/min/1,73 m2 pour le traitement par la dapagliflozine ou ≥ 20 ml/min/1,73 m2 pour le traitement par l'empagliflozine), mais leur effet diurétique osmotique peut entraîner un risque de déclin de la fonction rénale. Enfin, le traitement par les antagonistes des récepteurs mi-néralocorticoïdes devrait être envisagé pour tous les patients atteints d'ICEFR ayant un DFGe ≥ 30 ml/min/1,73 m2. Il convient d'instaurer le traitement avec une dose faible (p. ex., de 6,25 à 12,5 mg par jour ou 12,5 mg tous les deux jours) et d'ajuster la dose à la hausse selon la fonction rénale du patient et son taux de potassium sérique.

The Random Effects Warfarin Days' Supply (REWarDS) Model: Development and Validation of a Novel Method for Estimating Exposure to Warfarin Using Administrative Data.

Warfarin's complex dosing is a significant barrier to measurement of its exposure in observational studies using population databases. Using population-based administrative data (1996-2019) from British Columbia, Canada, we developed a method based on statistical modeling (Random Effects Warfarin Days' Supply (REWarDS)) that involves fitting a random-effects linear regression model to patients' cumulative dosage over time for estimation of warfarin exposure. Model parameters included a minimal universally available set of variables from prescription records for estimation of patients' individualized average daily doses of warfarin. REWarDS estimates were validated against a reference standard (manual calculation of the daily dose using the free-text administration instructions entered by the dispensing pharmacist) and compared with alternative methods (fixed window, fixed tablet, defined daily dose, and reverse wait time distribution) using Pearson's correlation coefficient (r), the intraclass correlation coefficient, and the root mean squared error. REWarDS-estimated days' supply showed strong correlation and agreement with the reference standard (r = 0.90 (95% confidence interval (CI): 0.90, 0.90); intraclass correlation coefficient = 0.95 (95% CI: 0.94, 0.95); root mean squared error = 8.24 days) and performed better than all of the alternative methods. REWarDS-estimated days' supply was valid and more accurate than estimates from all other available methods. REWarDS is expected to confer optimal precision in studies measuring warfarin exposure using administrative data.

Longitudinal Oral Anticoagulant Adherence Trajectories in Patients With Atrial Fibrillation.

BACKGROUND: Conventional adherence summary measures do not capture the dynamic nature of adherence. OBJECTIVES: This study aims to characterize distinct long-term oral anticoagulant adherence trajectories and the factors associated with them in patients with atrial fibrillation. METHODS: Adults with incident atrial fibrillation were identified using linked population-based administrative health data in British Columbia, Canada (1996-2019). Group-based trajectory modeling was used to model patients' 90-day proportions of days covered over time to identify distinct 5-year adherence trajectories. Multinomial regression analysis was used to assess the effect of various demographic and clinical factors on exhibiting each adherence trajectory. RESULTS: The study cohort included 19,749 patients with AF (mean age: 70.6 ± 10.6 years), 56% male, mean CHA2DS2-VASc stroke risk score 2.8 ± 1.4. Group-based trajectory modeling identified 4 distinct oral anticoagulants adherence trajectories: "consistent adherence" (n = 14,631, 74% of the cohort), "rapid decline and discontinuation" (n = 2,327, 12%), "rapid decline and partial recovery" (n = 1,973, 10%), and "slow decline and discontinuation" (n = 819, 4%). Very few patient variables were found to be associated with specific adherence trajectories. CONCLUSIONS: There is heterogeneity among nonadherent patients in the rate and timing of decline in their medication taking. Clinical and demographic characteristics were found to be inadequate to predict patients' adherence trajectories. Insights from this study could be used to inform the design and timing of adherence interventions, and qualitative studies may be needed to better understand the psychosocial determinants and reasons for the behaviors reflected in the identified trajectories.

Omega-3 fatty acids for the prevention of atherosclerotic cardiovascular disease.

Marine-derived omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are a type of polyunsaturated fatty acids with many purported beneficial health effects including the prevention of atherosclerotic cardiovascular disease (ASCVD) events. Omega-3 fatty acid intake may be supplemented via dietary sources, as well as prescription or non-prescription products. Omega-3 fatty acids have been shown to reduce serum triglycerides, but there remains ongoing debate regarding the effect of omega-3 fatty acids on major adverse cardiovascular events in patients with established, or at risk of, ASCVD. Recent evidence from randomized, placebo-controlled trials has demonstrated that low-dose (1 g daily or less) omega-3 fatty acids (DHA and EPA) do not reduce cardiovascular events or death in patients with or without established ASCVD. Contrarily, the REDUCE-IT trial demonstrated that a purified form of EPA ethyl esters (icosapent ethyl) at 4 g daily reduced cardiovascular events and death in patients with ASCVD (or diabetes and multiple cardiovascular risk factors) and elevated triglycerides on background statin therapy. However, 4 g daily of omega-3 carboxylic acids (DHA and EPA) did not show a cardiovascular benefit in the STRENGTH trial, which enrolled a similar population. The explanation for this observed discrepancy remains a source of contention and discourse. For now, icosapent ethyl has the most compelling evidence to support a cardiovascular benefit and should be considered in select patients who meet the REDUCE-IT criteria. Furthermore, alternative versions of omega-3 fatty acids should not be considered equivalent to icosapent ethyl. Patients taking an omega-3 fatty acid supplement should be monitored for potential adverse effects, including gastrointestinal disorders or bleeding, in addition to a possible increased risk of atrial fibrillation.