Heart Failure Related Outcomes in Patients within a Specialized Clinic-Based Cohort and a Population Level Cohort: Emphasis on Diabetes

• Author / Creator

  Gagnon, Luke R

• Diabetes mellitus (DM) is a well-established risk factor for adverse prognosis in patients with heart failure (HF). Outcomes in this patient population have not been thoroughly investigated in specialized heart function clinics (HFC). Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors have become a novel treatment for patients with HF. In addition to the natriuretic effect of SGLT2 inhibitors they likely have direct positive effects on the heart, proving to be efficacious in adults with HF based on randomized clinical trials.

  We aim to assess the initiation of SGLT2 inhibitors in HF patients with and without DM to assess utilization of this novel medication, as well as investigate more thoroughly the difference in HF patients with and without DM. We investigated outcomes of DM patients in a specialized HFC and compared to patients without DM, and their guideline-directed medical therapy (GDMT) utilization. Additionally, we compared SGLT2 inhibitor uptake and outcomes in two real-world cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a HFC cohort. The HFC cohort was created by chart review of patients seen in the HFC between February 2018 and August 2022. We examined GDMT utilization, baseline reported quality of life and outcomes amongst DM and non-DM cohort. The population-based cohort was derived from linked provincial healthcare datasets. We examined the association between SGLT2 inhibitor use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations.

  Of the 4,885 individuals with DM and HF in the population-based cohort, 64.2% met the eligibility criteria of the trials proving the efficacy of SGLT2 inhibitors, SGLT2 inhibitor usage increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients with DM and HF followed in the HFC, SGLT2 inhibitor use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2 inhibitor use in the population-based cohort was associated with fewer deaths (aHR 0.51, 95% CI 0.41–0.63) and fewer deaths/cardiovascular hospitalizations (aHR 0.65, 95% CI 0.54–0.77). SGLT2 inhibitor usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort).

  Within the HFC, patients with DM had higher rates of co-morbidities with the largest differences seen in hypertension (70.6% vs 43.8%), dyslipidemia (32.8% vs 16.9%) and chronic kidney disease (44.7% vs 26.1%), compared to those without DM (all p values < 0.001). Additionally, it was more common for patients with DM to have HF secondary to ischemic heart disease (p < 0.001). Patients without DM were more likely to have heart failure with preserved ejection fraction (HFpEF) compared to those with DM (p < 0.05). The main significant difference in GDMT utilization was SGLT2 inhibitor usage across all HF sub-types, which was much higher in the DM group (DM group = 33.8% vs. non-DM group = 3.1%, p < 0.001). In the heart failure with reduced ejection fraction (HFrEF) group for the overall cohort, GDMT utilization was 17.9% for SGLT2 inhibitors, 96.5% for beta-blocker, 82.0% for mineral corticoid receptor antagonists (MRA), and 94.6% for renin-angiotensin system (RAS) inhibitors. Additionally, In the HFrEF group for the overall cohort, 81.0% were on triple therapy and 16.0% on quadruple therapy. Patient-reported QoL was worse in those with DM (median 68.1, IQR: 45.8 – 87.5) compared to those without DM (76.0, IQR: 53.1 – 92.7, p < 0.001). When comparing patients based on ejection fraction only, QoL was significantly better in the heart failure with preserved ejection fraction (HFpEF) group compared to HFrEF and heart failure mildly reduced ejection fraction (HFmrEF) patients (p < 0.001). During a median follow-up time of 38.7 months (IQR: 30.7 – 48.2 months), patients with DM exhibited an increased risk of composite outcomes (aHR: 1.34, 95% CI 1.13 – 1.60) and all-cause mortality alone (aHR: 1.12, 95% CI 1.01 – 1.43) compared to non-DM patients.

  Our results critically highlight that HF patients with DM are a complex and vulnerable patient population, and special consideration for follow-up, management of comorbidities and rapid initiation of SGLT2 inhibitors should be given.

• Subjects / Keywords

  • Diabetes
  • SGLT2i
  • Heart Failure
  • Outcomes

• Graduation date

  Fall 2024

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-v23x-we39

• License

  This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.