CANVAS (canagliflozin)
Trial question
What is the effect of canagliflozin in patients with T2DM and high cardiovascular risk?
Study design
Multi-center
Single blinded
RCT
Population
Characteristics of study participants
36.0% female
64.0% male
N = 10142
10142 patients (3633 female, 6509 male).
Inclusion criteria: patients with T2DM and high cardiovascular risk.
Key exclusion criteria: history of diabetic ketoacidosis, TIDM, pancreas or β-cell transplantation, renal disease requiring treatment with immunosuppressive therapy, history of chronic dialysis or renal transplant.
Interventions
N=5795 canagliflozin (at a dose of 300 mg or 100 mg in CANVAS and initial dose of 100 mg daily with an optional increase to 300 mg starting from week 13 in CANVAS-R).
N=4347 placebo (matching placebo).
Primary outcome
CV death, nonfatal MI, or nonfatal stroke
26.9
31.5
31.5
23.6
15.8
7.9
0.0
Canagliflozin
Placebo
Significant
decrease ▼
Significant decrease in CV death, nonfatal MI, or nonfatal stroke (26.9 vs. 31.5; HR 0.86, 95% CI 0.75 to 0.97).
Secondary outcomes
Significant decrease in progression of albuminuria (89.4 vs. 128.7; HR 0.73, 95% CI 0.67 to 0.79).
Safety outcomes
No significant differences in adverse events leading to discontinuation (35.5 vs. 32.8 patients per 1,000 patient-years; HR 1.13, 95% CI 0.99-1.28).
Significant differences in risk of amputation of toes, feet, or legs (6.3 vs. 3.4 patients per 1,000 patient-years; HR 1.97, 95% CI 1.41-2.75) and serious adverse events (104.3 vs. 120.0 patients per 1,000 patient-years; HR 0.93, 95% CI 0.87-1.00).
Conclusion
In patients with T2DM and high cardiovascular risk, canagliflozin was superior to placebo with respect to CV death, nonfatal MI, or nonfatal stroke.
Reference
Neal B, Perkovic V, Mahaffey KW et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657.
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