Summary

• In the CREDENCE study, hospitalized heart failure (HF) occurred at a rate of 15.7 (n=89/2202) and 25.3 (n=141/2199) events per 1000 patient-years in the INVOKANA and placebo (PBO) groups, respectively (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.47-0.80); P<0.001).¹
• In the CANVAS Program, hospitalized congestive heart failure (HHF) occurred at a rate of 5.5 vs 8.7 events per 1000 patient-years in the INVOKANA and PBO groups, respectively (HR, 0.67; 95% CI, 0.52-0.87).²
• In pooled data from 7 active- and PBO-controlled, phase 3 INVOKANA clinical studies^3-10, congestive HF was reported in 9 (0.1%) patients in the combined INVOKANA group (including 100-mg and 300-mg groups, n=6177) and in 10 (0.3%) patients in the nonINVOKANA group (n=3262).¹¹
• An additional citation identified during a literature search has been included in the REFERENCES section for your review.¹²

CLINICAL STUDIES

CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) was a randomized, double-blind, PBO-controlled, parallel group multicenter, event-driven study (N=4401) designed to assess the effects of INVOKANA 100 mg compared to PBO on clinically important renal outcomes in people with type 2 diabetes mellitus (T2DM) and established chronic kidney disease (estimated glomerular filtration rate 30 to <90 mL/min/1.73 m²) and albuminuria (ratio of albumin to creatinine >300 to 5000 mg/g), who were receiving a stable, maximum tolerated or labeled dose (for >4 weeks prior to randomization) of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.^{1, 13-17} Median follow-up was ~2.62 years.

• Patients with a current or history of HF of New York Heart Association Class IV cardiac disease were excluded from the study.¹⁵
• HHF was included as a stand-alone secondary efficacy outcome, as well as part of a composite with cardiovascular (CV) death, and a broader CV composite with CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalized unstable angina.¹
• At baseline, 14.8% (n=652) of the total population had a history of HF.¹⁴
• Hospitalized HF occurred at a rate of 15.7 (n=89/2202) and 25.3 (n=141/2199) events per 1000 patient-years in the INVOKANA and PBO groups, respectively (HR, 0.61; 95% CI, 0.47-0.80; P<0.001).¹

The CANVAS Program comprised 2 large INVOKANA CV outcome studies, CANVAS (CANagliflozin cardiovascular Assessment Study)^{7, 18} and CANVAS-R,^{19, 20} and included a prespecified integrated analysis to meet the Food and Drug Administration postmarketing requirement for CV safety, as well as evaluate potential for CV protection of INVOKANA in T2DM patients with prior history of CV disease or ≥2 CV risk factors.^{2, 21, 22} Mean follow-up time was 188.2 weeks.

• HHF was included as a prespecified exploratory CV outcome.²
• At baseline, 14.4% of the total population had a history of HF.
• HHF occurred at a rate of 5.5 vs 8.7 events per 1000 patient-years in the INVOKANA and PBO groups, respectively (HR, 0.67; 95% CI, 0.52-0.87).²
• Of the 10,142 patients in the CANVAS Program, 276 experienced a fatal or hospitalized HF event during follow-up, with 61 patients having more than one event.²³

In pooled data from 7 active- and PBO-controlled, phase 3 INVOKANA clinical studies^3-10, congestive HF was reported in 9 (0.1%) patients in the combined INVOKANA group (including 100-mg and 300-mg groups, n=6177) and in 10 (0.3%) patients in the nonINVOKANA group (n=3262).¹¹

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 11 March 2023.