Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and Women Without Diabetes at Baseline: A Population-Based Study of 608 474 Adults.

BACKGROUND: We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline. METHODS AND RESULTS: This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3-year enrollment period. The primary outcome of CVD hospitalization and secondary outcome of combined CVD hospitalization/mortality were examined during a 5-year follow-up period until March 31, 2021. A total of 608 474 individuals (55.2% women) were included. Compared with HbA1c 5.0% to 5.4%, men with HbA1c of 5.5% to 5.9% had an increased risk of CVD hospitalization (adjusted hazard ratio [aHR], 1.12 [95% CI, 1.07-1.19]) whereas women did not (aHR, 1.01 [95% CI, 0.95-1.08]). Men and women with HbA1c of 6.0% to 6.4% had a 38% and 17% higher risk and men and women with HbA1c ≥6.5% had a 79% and 51% higher risk of CVD hospitalization, respectively. In addition, HbA1c of 6.0% to 6.4% and HbA1c ≥6.5% were associated with a higher risk (14% and 41%, respectively) of CVD hospitalization/death in men, but HbA1c ≥6.5% was associated with a 24% higher risk only among women. CONCLUSIONS: In both men and women, HbA1c ≥6.0% was associated with an increased risk of CVD and mortality outcomes. The association between CVD and HbA1c levels of 5.5% to 5.9%, considered to be in the "normal" range, highlights the importance of optimizing cardiovascular risk profiles at all levels of glycemia, especially in men.

Association between sodium-glucose cotransporter-2 inhibitors and arrhythmic outcomes in patients with diabetes and pre-existing atrial fibrillation.

AIMS: Prior studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. METHODS AND RESULTS: We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55-0.96; P = 0.03)]. Sodium-glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. CONCLUSION: Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is.

Sodium-glucose co-transporter-2 inhibitors are associated with kidney benefits at all degrees of albuminuria: A retrospective cohort study of adults with diabetes.

AIM: To estimate the real-world effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) at reducing loss of kidney function and adverse kidney events in adults with varying levels of albuminuria. MATERIALS AND METHODS: In this retrospective cohort study using administrative data, we matched new SGLT2i users 1:2 to DPP4i users on diabetes therapy, chronic kidney disease (CKD) stage, albuminuria and time-conditional propensity score. Albuminuria was defined by spot urine albumin or equivalent as mild, moderate or severe. Linear regression was used to model the estimated glomerular filtration rate (eGFR), and Poisson regression for a composite kidney outcome (> 40% loss of eGFR, kidney replacement therapy or death from kidney causes) and all-cause mortality. RESULTS: SGLT2i users (n = 19 238, median age 57.9 years, female 40.9%) had mostly nil/mild albuminuria (70.7%). SGLT2is were associated with a 1.36 (95% CI 0.98-1.74) mL/min/1.73m2 (P < .001) acute (≤ 60 days) decline in eGFR, relative to DPP4is. Thereafter, SGLT2is were associated with 1.04 (95% CI 0.93-1.15) mL/min/1.73m2 (P < .001) less annual eGFR loss. SGLT2i users had fewer adverse kidney outcomes (incidence rate ratio [IRR] 0.58 [0.47-0.71]; P < .001), but not all-cause mortality (IRR 0.82 [0.66-1.01]; P = .06). Outcomes were similar considering only those with nil/mild albuminuria. CONCLUSIONS: SGLT2is may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes and nil or non-severe albuminuria.

In obesity or overweight without diabetes, orforglipron increased weight loss at 26 wk.

SOURCE CITATION: Wharton S, Blevins T, Connery L, et al; GZGI investigators. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med. 2023;389:877-880. 37351564.

In prediabetes, oral vitamin D reduces progression to new-onset diabetes.

SOURCE CITATION: Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and risk for type 2 diabetes in people with prediabetes: a systematic review and meta-analysis of individual participant data from 3 randomized clinical trials. Ann Intern Med. 2023;176:355-363. 36745886.

Anticoagulation in type 2 myocardial infarctions: Lessons learned from the rivaroxaban in type 2 myocardial infarctions feasibility trial.

Background: Type 2 myocardial infarction (T2MI) occurs when myocardial oxygen demand exceeds myocardial oxygen supply. T2MIs occur more frequently and have worse outcomes compared to Type 1 myocardial infarction caused by an acute plaque rupture. No clinical trial evidence is available to guide pharmacological therapies in this high-risk population. Methods: The Rivaroxaban in Type 2 Myocardial Infarction (R2MI) trial (NCT04838808) was a trainee-led, pragmatic, pilot study that randomised patients with a T2MI to either rivaroxaban 2.5 mg twice daily or placebo. The trial was stopped early due to low recruitment. Investigators explored the challenges of conducting the trial in this population. This was supplemented by a retrospective chart review of 10,000 consecutive troponin assays undertaken during the study period. Results: Over a 1-year period, 276 patients with T2MI were screened for inclusion of which only 7 (2.5%) were randomised in the trial. Study investigators identified trial design and participant population factors that limited recruitment. These included: heterogeneity of patient presentation, poor clinical prognosis, and lack of dedicated non-trainee study personnel. The major limitation to recruitment was the frequency of identified exclusion criterion. The retrospective chart review identified 1715 patients with an elevated high-sensitivity troponin level, of which 916 (53%) were adjudicated to be related to T2MI. Of these, 94.5% possessed an exclusion criterion for the trial. Conclusion: Patients with a T2MI are challenging to recruit into clinical trials involving oral anticoagulation. Future studies should account for only ∼1 in every 20 screened individuals being a candidate for study recruitment.

Atteinte des cibles thérapeutiques pour le diabète de type 2 en 2015 et 2020 en médecine de soins primaires au Canada.

CONTEXTE: Une vérification du degré d'atteinte des cibles thérapeutiques pour le diabète de type 2 au Canada s'impose afin d'en documenter l'évolution et d'identifier les sousgroupes auprès desquels il est plus urgent d'intervenir. Nous avons voulu estimer la fréquence à laquelle les cas suivis en soins primaires atteignaient leurs cibles thérapeutiques (c.-a-d., HbA1c ≤ 7,0 %, tension artérielle (TA) < 130/80 mm Hg et cholestérol à lipoprotéines de basse densité [LDL-C] < 2,00 mmol/L), le recours aux statines et aux inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA) ou aux bloqueurs des récepteurs de l'angiotensine (BRA) conformément aux lignes directrices, et les effets de l'âge et du sexe. MÉTHODES: Nous avons réalisé une étude transversale auprès de 32 503 et 44 930 adultes atteints de diabète au Canada le 30 juin 2015 et le 30 juin 2020, respectivement, à l'aide des données tirées des dossiers médicaux électroniques (DME) des milieux de soins primaires de 5 provinces. Nous avons regroupé l'atteinte des cibles thérapeutiques pour le diabète selon l'âge et le sexe et comparé les groupes à l'aide d'analyses de régression logistique en tenant compte des comorbidités cardiovasculaires. RÉSULTATS: En 2020, les taux cibles d'HbA1c ont été atteints par 63,8 % des femmes et 58,9 % des hommes. Les cibles de TA et de LDL-C ont été atteintes par 45,6 % et 45,8 % des femmes et par 43,1 % et 59,4 % des hommes, respectivement. Les 3 cibles thérapeutiques ont été atteintes par 13,3 % des femmes et 16,5 % des hommes. Globalement, 45,3 % et 54,0 % des femmes et des hommes, respectivement, ont utilisé des statines; 46,5 % des femmes ont utilisé des inhibiteurs de l'ECA ou des BRA, contre 51,9 % des hommes. À l'exception de la TA et des taux d'HbA1c chez les femmes, l'atteinte des cibles a été moindre chez les patientes plus jeunes. L'atteinte de la cible de LDL-C et l'utilisation de statines et d'IECA ou de BRA ont été moindres chez les femmes de toutes les catégories d'âge. Entre 2015 et 2020, l'atteinte des cibles a augmenté pour l'HbA1c, est demeurée constante pour le LDL-C et a diminué pour la TA; l'utilisation des statines et des IECA ou des BRA a aussi diminué. INTERPRÉTATION: L'atteinte des cibles de TA et l'utilisation des statines, des IECA et des BRA ont diminué entre 2015 et 2020 et étaient sous-optimales dans tous les groupes. Une amélioration à grande échelle de la qualité des soins s'impose pour promouvoir un traitement du diabète fondé sur des données probantes.

Achievement of treatment targets among patients with type 2 diabetes in 2015 and 2020 in Canadian primary care.

BACKGROUND: An update on the degree to which patients with type 2 diabetes in Canada achieve treatment targets is needed to document progress and identify subgroups that need attention. We sought to estimate the frequency with which patients managed in primary care met treatment targets (i.e., HbA1c ≤ 7.0%, blood pressure < 130/80 mm Hg and low-density lipoprotein cholesterol [LDL-C] < 2.00 mmol/L), guideline-based use of statins and of angiotensin-convertingenzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and the effects of patient age and sex. METHODS: We conducted a cross-sectional study of 32 503 and 44 930 adults with diabetes in Canada on June 30, 2015, and 2020, respectively, using electronic medical record data from primary care practices across 5 provinces. We grouped achievement of diabetes targets by age and sex, and compared between groups using logistic regression with adjustment for cardiovascular comorbidities. RESULTS: In 2020, target HbA1c levels were achieved for 63.8% of women and 58.9% of men. Blood pressure and LDL-C targets were achieved for 45.6% and 45.8% of women, and for 43.1% and 59.4% of men, respectively. All 3 treatment targets were achieved for 13.3% of women and 16.5% of men. Overall, 45.3% and 54.0% of women and men, respectively, used statins; 46.5% of women used ACE inhibitors or ARBs, compared with 51.9% of men. With the exception of blood pressure and HbA1c levels among women, target achievement was lower among younger patients. Achievement of the LDL-C target, statin use and ACE inhibitor or ARB use were lower among women at any age. From 2015 to 2020, target achievement increased for HbA1c, remained consistent for LDL-C and declined for blood pressure; use of statins and of ACE inhibitors or ARBs also declined. INTERPRETATION: Target achievement for blood pressure and use of statins and of ACE inhibitors and ARBs declined between 2015 and 2020, and was suboptimal in all patient groups. Widespread quality improvement is needed to increase evidence-based therapy for people with diabetes.

Use of sodium-glucose cotransporter 2 inhibitors in Alberta adults with chronic kidney disease: a cross-sectional study identifying care gaps to inform knowledge translation.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have important kidney and cardiovascular benefits in adults with chronic kidney disease. Among adults with diabetes, we characterized the prevalence of chronic kidney disease eligible for SGLT2 inhibitor treatment, based on definitions of eligibility from trials and diabetes guidelines, and assessed the predictors of SGLT2 inhibitor use. METHODS: We conducted a cross-sectional study using linked administrative data from Alberta Health in adults with diabetes (2002-2019). Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2 with severe or greater proteinuria (trial-based definition); or eGFR less than 60 mL/min/1.73 m2 or moderate or greater proteinuria regardless of eGFR (diabetes guideline-based definition). Predictors (sociodemographic characteristics, comorbidities and health care utilization) of SGLT2 inhibitor use were identified using logistic regression. RESULTS: Of 446 315 adults with diabetes, 76 630 (17.2%, guideline-based definition; 12 867 [2.9%], trial-based definition) had chronic kidney disease eligible for SGLT2 inhibitor treatment. A total of 7.1% used SGLT2 inhibitors. Older age, lower hemoglobin A1c (HbA1c) levels, female sex, lower neighbourhood income, rural residence and hospital admission were among variables associated with nonuse of SGLT2 inhibitors (adjusted odds ratios [ORs] from 0.13 [age ≥ 85 yr] to 0.92 [rural residence], p < 0.05). Family physician visits were associated with higher SGLT2 inhibitor use (adjusted OR 4.01, p < 0.001 for > 4 visits/yr). Considering all adults, both with and without diabetes, 162 012 individuals with chronic kidney disease (5% of all Alberta adults) may benefit from treatment with SGLT2 inhibitors. INTERPRETATION: Many adults with chronic kidney disease would derive heart and kidney benefits from treatment with SGLT2 inhibitors but had low SGLT2 inhibitor use as of 2019. Efforts will be needed to address lower use of SGLT2 inhibitors among female, older and lower-income adults, and to enhance primary care and promote awareness of the benefits of SGLT2 inhibitors independent of glycemic control.

Improving incident reporting among physicians at south health campus hospital.

Reports of adverse events and near-misses provide the opportunity to learn about latent (systems) errors. However, voluntary incident reporting systems are underused by physicians. While reports submitted by nursing staff relate to common hazards such as medication administration or falls, physicians have broader exposure to patients' entire hospital journey. Reports by physicians have the potential to uncover more serious errors that could span multiple departments and layers of personnel. Organisational safety culture thrives when all staff are represented and feel empowered to share safety concerns.At the South Health Campus (SHC) Hospital in Calgary, Alberta, Canada, the baseline proportion of physician-submitted reports within our site's Reporting and Learning System (RLS) from July 2013 to December 2016 was 1.12%. We implemented an intervention to double the proportion of physician-submitted RLS reports, using quality improvement methods.Focus groups identified lack of experience with the RLS system, lack of feedback or closure after an RLS submission, and apprehensions about disclosing the incident to the affected patient as barriers to physician submission. Accordingly, the intervention involved direct responses from physician leadership to each physician-submitted RLS report, multimedia demonstrations of efficient RLS submission to physician groups and medical learners, and linkage to materials on safe disclosures. Effectiveness was assessed using a controlled before-and-after design, comparing SHC with the rest of Calgary and with the rest of Alberta.Following the intervention, the proportion of RLS reports that were physician submitted increased to 2.65% (OR 2.42 [95% CI 1.96 to 3.02], p<0.001), sustained over the following 4 years. While an increase was observed for the rest of Calgary, it was smaller (OR 1.27 [1.15 to 1.40], p<0.001). A decrease in the odds of physician submission was observed for the rest of Alberta. Differences between sites were significant (p<0.001).Overall, we found that physician-submitted incident reports can be increased and sustained over time if submitters receive personalised feedback by a physician safety leader. At our site, reports submitted by physicians have been valuable in uncovering complex systems issues that may not have been readily apparent.

Telemonitoring and protocolized case management for hypertensive community dwelling older adults (TECHNOMED): a randomized controlled trial.

BACKGROUND: Home blood pressure (BP) telemonitoring combined with case management leads to BP reductions in individuals with hypertension. However, its benefits are less clear in older (age ≥ 65 years) adults. METHODS: Twelve-month, open-label, randomized trial of community-dwelling older adults comparing the combination of home BP telemonitoring (HBPM) and pharmacist-led case management, vs. enhanced usual care with HBPM alone. The primary outcome was the proportion achieving systolic BP targets on 24-h ambulatory BP monitoring (ABPM). Changes in HBPM were also examined. Logistic and linear regressions were used for analyses, adjusted for baseline BP. RESULTS: Enrollment was stopped early due to coronavirus disease 2019. Participants randomized to intervention (n = 61) and control (n = 59) groups were mostly female (77%), with mean age 79.5 years. The adjusted odds ratio for ABPM BP target achievement was 1.48 (95% confidence interval 0.87-2.52, P = 0.15). At 12 months, the mean difference in BP changes between intervention and control groups was -1.6/-1.1 for ABPM (P-value 0.26 for systolic BP and 0.10 for diastolic BP), and -4.9/-3.1 for HBPM (P-value 0.04 for systolic BP and 0.01 for diastolic BP), favoring the intervention. Intervention group participants had hypotension (systolic BP < 110) more frequently (21% vs. 5%, P = 0.009), but no differences in orthostatic symptoms, syncope, non-mechanical falls, or emergency department visits. CONCLUSIONS: Home BP telemonitoring and pharmacist case management did not improve achievement of target range ambulatory BP, but did reduce home BP. It did not result in major adverse consequences.

New Diabetes Guidelines: Impact on Eligibility for Sodium-glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Canada.

OBJECTIVES: Recent diabetes guidelines call for prescribing sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) for end-organ indications (cardiovascular disease [CVD], heart failure and chronic kidney disease) and for primary prevention of CVD in adults with multiple risk factors. Our aim was to assess the effect of new guidelines on the prevalence of SGLT2i/GLP-1RA-eligible adults, and their current rates of SGLT2i/GLP-1RA use. METHODS: Cross-sectional study of Canadian adults (age ≥18 years) with diabetes on June 30, 2020, using electronic medical record data from primary care practices in 5 provinces (Alberta, Manitoba, Newfoundland, Ontario and Québec). Indications were determined from comorbidities, lab values and cardiovascular risk factors. RESULTS: End-organ indications were present in 34.1% of adults for SGLT2i, and in 17.1% for GLP-1RA (CVD only). Rates of SGLT2i and GLP-1RA use were only 14.0% and 4.3%, respectively, in those with end-organ indications. The majority of these individuals had glycated hemoglobin ≤7.0%. The combination of end-organ and primary prevention indications increased eligibility for SGLT2i to 62.6%, and for GLP-1RA to 59.1%. CONCLUSIONS: The implications of this sizeable reclassification of adults as SGLT2i/GLP-1RA indicated on health-care budgets and cost-effectiveness requires further study. In the meantime, targeted efforts are necessary to improve SGLT2i/GLP-1RA use in those with end-organ indications that have robust evidence of cardiovascular and kidney benefit from newer agents.

Foregone Opportunities? Time to Treatment Intensification Among Adults With Type 2 Diabetes and Elevated Glycated Hemoglobin on Metformin Monotherapy, 2009-2018.

OBJECTIVES: In this study, we aimed to characterize time to treatment intensification (TTI) in people on metformin with uncontrolled hyperglycemia, and estimated the frequency of physician visits until intensification. METHODS: This work was a cohort study of Albertan adults with glycated hemoglobin (A1C) of >7.5% after at least 3 months of metformin monotherapy, using administrative databases from 2009 to 2018, with each subject followed for up to 4 years. Therapeutic intensification was defined as dispensation of an additional class of antihyperglycemic medication. Median TTI and the median number of physician visits were estimated from Kaplan-Meier functions within age/A1C strata. A Cox proportional hazards model was fitted to examine predictors of therapeutic intensification. RESULTS: We included 38,846 people (average age, 57 years; 37% female; mean A1C, 8.8%). Overall, therapeutic intensification was observed in 23,077 (59%; 40% at 1 year). Median TTI was 1.4 years, varying from 0.7 years (A1C >8.5%, age <65 years) to 3.3 years (age ≥75 years, any A1C). The median number of physician visits until intensification was 9, varying between 5 (A1C >8.5%, age <65 years) and ≥30 (age ≥75 years); 93% of people awaiting intensification had at least 2 visits by 1 year. Higher A1C and younger age were the strongest predictors of intensification. Results were similar in people with ischemic heart disease. CONCLUSIONS: Despite ample contacts with community physicians, TTI exceeds the 6-month target recommended by guidelines, particularly in older adults. Further study is needed to better understand these foregone opportunities as guidelines call for wider promulgation of agents with cardiorenal benefits.

Underuse of cardiorenal protective agents in high-risk diabetes patients in primary care: a cross-sectional study.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown benefits in patients with diabetes and cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD). OBJECTIVE: We assessed benchmark outcomes (Hemoglobin A1c, LDL-C, and blood pressure), identified the prevalence of cardiorenal indications for SGLT2i and GLP-1RA, and compared prescribing rates of GLP1-RA and SGLT2i in those with and without cardiorenal indications. METHODS: We analyzed data from January 2018-June 2019 for 7168 patients with diabetes using electronic medical records from the Northern Alberta Primary Care Research Network, a regional network of the Canadian Primary Sentinel Surveillance Network (CPCSSN). Patients with and without cardiorenal comorbidities were compared using descriptive statistics and two proportion Z tests. RESULTS: Hemoglobin A1c ≤ 7.0% was met by 56.8%, blood pressure < 130/80 mmHg by 62.1%, LDL-C ≤ 2.0 mmol/L by 45.3% of patients. There were 4377 patients on glucose lowering medications; metformin was most common (77.7%), followed by insulin (24.6%), insulin secretagogues (23.6%), SGLT2i (19.7%), dipeptidyl peptidase-4 inhibitor (19.3%), and GLP-1RA (9.4%). A quarter of patients had cardiorenal indications for SGLT2i or GLP-1RA. Use of SGLT2i in these patients was lower than in patients without cardiorenal comorbidities (14.9% vs 21.2%, p < 0.05). GLP-1RA use in these patients was 4.6% compared with 11% in those without cardiorenal comorbidities (p < 0.05). DISCUSSION: Contrary to current evidence and recommendations, SGLT2i and GLP1-RA were less likely to be prescribed to patients with pre-existing CVD, HF, and/or CKD, revealing opportunities to improve prescribing for patients with diabetes at high-risk for worsening cardiorenal complications.

In uninfected household contacts of patients with COVID-19, REGEN-COV reduced symptomatic COVID-19 at 28 d.

SOURCE CITATION: O'Brien MP, Forleo-Neto E, Musser BJ, et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med. 2021;385:1184-95. 34347950.

In adults with overweight or obesity, continued weekly semaglutide after a 20-wk run-in improved weight loss.

SOURCE CITATION: Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325:1414-25. 33755728.

Cost-Utility of Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure: An Economic Evaluation.

Background Recent trials comparing catheter ablation to medical therapy in patients with heart failure (HF) with symptomatic atrial fibrillation despite first-line management have demonstrated a reduction in adverse outcomes. We performed an economic evaluation to estimate the cost-utility of catheter ablation as second line therapy in patients with HF with reduced ejection fraction. Methods and Results A Markov model with health states of alive, dead, and alive with amiodarone toxicity was constructed, using the perspective of the Canadian healthcare payer. Patients in the alive states were at risk of HF and non-HF hospitalizations. Parameters were obtained from randomized trials and Alberta health system data for costs and outcomes. A lifetime time horizon was adopted, with discounting at 3.0% annually. Probabilistic and 1-way sensitivity analyses were performed. Costs are reported in 2018 Canadian dollars. A patient treated with catheter ablation experienced lifetime costs of $64 960 and 5.63 quality-adjusted life-years (QALY), compared with $49 865 and 5.18 QALYs for medical treatment. The incremental cost-effectiveness ratio was $35 360/QALY (95% CI, $21 518-77 419), with a 90% chance of being cost-effective at a willingness-to-pay threshold of $50 000/QALY. A minimum mortality reduction of 28%, or a minimum duration of benefit of >1 to 2 years was required for catheter ablation to be attractive at this threshold. Conclusions Catheter ablation is likely to be cost-effective as a second line intervention for patients with HF with symptomatic atrial fibrillation, with incremental cost-effectiveness ratio $35 360/QALY, as long as over half of the relative mortality benefit observed in extant trials is borne out in future studies.