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Published on: November 29, 2024
Early Longitudinal Change in Heart Failure Health Status Following Initiation of Canagliflozin
Reza Mohebi1, Philip G Jones2, John A Spertus2
1Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy rapidly improves heart failure (HF) symptoms, with significant gains seen within the first weeks of treatment for both HFpEF and HFrEF patients.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Sodium glucose co-transporter 2 inhibitors (SGLT2i) are known to improve health status in heart failure (HF).
- Limited data exists on the precise timing and magnitude of health status changes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) following SGLT2i initiation.
Purpose of the Study:
- To model the association between canagliflozin treatment and the rate of change in HF symptom status.
- To analyze symptom changes in both HFpEF and HFrEF populations.
Main Methods:
- A 12-week randomized controlled trial involving 448 HF patients (181 HFrEF, 267 HFpEF) treated with canagliflozin or placebo.
- The Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) was measured at baseline and at weeks 2, 4, 6, and 12.
- Longitudinal modeling was employed to assess the slope of KCCQ-TSS change.
Main Results:
- HFpEF patients exhibited lower baseline KCCQ-TSS scores compared to HFrEF patients (54 ± 21 vs. 64 ± 20).
- Canagliflozin treatment led to rapid initial improvements in KCCQ-TSS for both HF groups, with improvement rates decelerating after 4-6 weeks.
- While HFpEF patients showed a numerically greater improvement rate (0.7 points/day) than HFrEF patients (0.5 points/day), the difference was not statistically significant.
Conclusions:
- Canagliflozin therapy demonstrably enhances KCCQ-TSS scores rapidly in HF patients, irrespective of ejection fraction.
- The most substantial health status improvements are observed within the initial weeks of SGLT2i treatment.
- Findings support the clinical utility of SGLT2is in HF management and inform future clinical trial designs focused on health status outcomes.
Background:
Sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy improves health status in heart failure (HF). There is insufficient description regarding the timing, rate, and extent of the health status changes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) after initiation of SGLT2is.
Objectives:
The authors sought to model the association of canagliflozin treatment with rates of change in HF symptom status in HFpEF and HFrEF.
Methods:
Study participants with HFrEF and HFpEF were treated with either canagliflozin 100 mg or placebo for 12 weeks. The Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) was assessed at baseline and at 2, 4, 6, and 12 weeks. Longitudinal modeling assessed slope of KCCQ change across the study.
Results:
Among 448 individuals with HF (181 with HFrEF and 267 with HFpEF), participants with HFpEF had lower baseline KCCQ-TSS scores than those with HFrEF (54 ± 21 vs 64 ± 20). Modeling demonstrated initial rapid improvement in KCCQ-TSS in both HF groups, with deceleration over the next 4 to 6 weeks. The rate of change was greater among HFpEF participants (0.7 points/day; 95% CI: 0.3-1.1 points/day) than HFrEF participants (ΔKCCQ-TSS/day = 0.5; 95% CI: 0.1-1.0 points/day) randomized to canagliflozin, but these differences were not statistically significant (0.2 points/day; 95% CI: -0.4 to 0.7 points/day; P = 056).
Conclusions:
After canagliflozin therapy, regardless of EF, modeling shows the KCCQ-TSS improves rapidly with the greatest improvements occurring within the first weeks of treatment. These results have implications for clinical use of SGLT2is and may be useful in the design of trials examining impact of these agents on health status in HF. (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure [CHIEF-HF]; NCT04252287).
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