Canagliflozin is found to have reduced risk of cardiovascular death or hospitalization due to heart failure in type 2 diabetes patients.
Type 2 diabetes is associated with many risks, including the development of cardiovascular and renal disease. Some of the cardiovascular complications include heart failure, volume overload, kidney failure, and even death. Thus far, no other glucose-lowering medication other than sodium glucose cotransporter 2 (SGL2) inhibitors has shown to reduce heart failure hospitalization. In fact, some diabetes medications cause increased risk of heart failure such as dipeptidyl peptidase -4 inhibitors and thiazolidinedione. Two clinical trials have shown reduction in the risk of heart-failure-associated hospitalization from use of empagliflozin. This study studied the effects of canagliflozin on heart failure and determined its safety and efficacy in participants with and without history of heart failure at baseline.
This CANVAS trial was designed to assess cardiovascular and renal safety and efficacy of canagliflozin. Canagliflozin was compared with placebo in order to compare benefits against risks. A total of 10,412 participants included in this trial were both men and women with type 2 diabetes with A1C > 7% and mean follow up time of 188.2 weeks. Participants greater than 30 years of age with a history of symptomatic atherosclerotic cardiovascular disease or greater than 50 years of age with ≥ 2 risk factors for cardiovascular disease were included in this study.
Risk factors for cardiovascular disease included duration of diabetes >10 years, systolic blood pressure >140 mmHg while being on more than one antihypertensive agents, current smoker, microalbuminuria or macroalbuminuria, or high-density lipoprotein cholesterol < 1 mmol/L.
Patients diagnosed with Class IV heart failure were excluded from this study.
Participants in this CANVAS trial were randomly assigned in 1: 1: 1 ratio to receive canagliflozin 300mg, canagliflozin 100mg, or a placebo and participants in CANVAS-R study were randomly assigned in 1: 1 ratio to receive either canagliflozin or placebo. The primary outcome was the total number of hospitalizations due to heart failure or cardiovascular death from sudden myocardial infarction, stroke, or cardiac death. Secondary outcomes included serious kidney function decline, nonfatal myocardial infarction, nonfatal stroke, and fatal or hospitalized heart failure.
A total of 65.6% of participants had a history of cardiovascular disease at baseline and 14.4% of participants had a history of heart failure at baseline. Some of these patients were not only using diabetes therapy but were also using medications for management of heart failure, including diuretics, renin angiotensin aldosterone system blockers, beta blockers, and statins. There were a total of 203 and 449 cardiovascular deaths or hospitalized heart-failure incidences reported among participants who reported a history of heart failure at baseline and those who did not, respectively.
Results of this study found that when canagliflozin was compared to placebo, canagliflozin was significantly associated with lower risks of cardiovascular deaths or hospitalized heart failure. This benefit on cardiovascular death or hospitalization due to heart failure was not significantly greater in patients with prior history of heart failure compared to those who did not have any history at baseline. Heart failure can also be affected by other risk factors such as patient’s age, their renal function, and other disease history. Furthermore, participants receiving canagliflozin had significantly less recurrent hospitalization due to heart failure compared to placebo. Different doses of canagliflozin (100mg vs 300mg) did not have any significant difference on cardiovascular mortality or hospitalized heart failure rate.
Canagliflozin was found to have increased adverse effects compared to placebo, including increased risks of amputation, fracture, and volume depletion. Although non-significant results were found, it is believed by the authors that the benefit of canagliflozin may be greater in patients with a history of heart failure compared to those without. In conclusion, canagliflozin has great benefits in reducing the risk of cardiovascular death and hospitalization due to heart failure across a broad range of patient population and therefore should be considered as a therapy for use in patients with type 2 diabetes.
- Canagliflozin was found to have lower risk of cardiovascular death or hospitalized heart failure when compared to placebo.
- Use of canagliflozin had less recurrent hospitalization due to heart failure when compared to placebo.
- Canagliflozin was found to have more adverse effects than placebo treatment.
Radholm K, Figtree G, Perkovic V et al. Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus. Circulation. 2018; 137:00-00.
Vidhi Patel, Pharm. D. Candidate 2018, LECOM School of Pharmacy