Canagliflozin Cardiovascular Assessment Study - CANVAS

Contribution To Literature:

The CANVAS trial showed that canagliflozin was superior at preventing cardiovascular events.

Description:

The goal of the trial was to evaluate the sodium-glucose cotransporter 2 inhibitor canagliflozin compared with placebo among patients with type 2 diabetes.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Blinded

Patients with type 2 diabetes were randomized to canagliflozin (n = 5,795) versus placebo (n = 4,347). Patients in the canagliflozin arm received 300 mg daily or 100 mg daily.

Inclusion criteria:

  • Patients with type 2 diabetes and high cardiovascular risk
  • ≥30 years of age and history of symptomatic atherosclerotic cardiovascular disease, or
  • ≥50 years of age and 2+ of the following: diabetes duration >10 years, systolic blood pressure >140 mm Hg on antihypertensive therapy, current smoking, albuminuria, or high-density lipoprotein cholesterol <38.7 mg/dl
  • Total number of enrollees: 10,142
  • Duration of follow-up: 188 weeks
  • Mean patient age: 63 years
  • Percentage female: 36%
  • Percentage with diabetes: 100%

Other salient features/characteristics:

  • Mean duration of diabetes: 13.5 years
  • 65.6% of participants had history of cardiovascular disease

Principal Findings:

The primary outcome, incidence of cardiovascular death, myocardial infarction, or stroke, occurred in 26.9 participants per 1,000 patient-years of the canagliflozin group versus 31.5 participants per 1,000 patient-years of the placebo group (p = 0.02 for superiority, p < 0.001 for noninferiority).

Secondary outcomes

  • Amputation: 6.3 participants per 1,000 patient-years versus 3.4 participants per 1,000 patient-years (p < 0.05)
  • Progression of albuminuria: 89.4 participants per 1,000 patient-years versus 128.7 participants per 1,000 patient-years (p < 0.05)

Interpretation:

Among patients with type 2 diabetes, canagliflozin was beneficial. Canagliflozin compared with placebo was associated with a lower frequency of adverse cardiovascular events. Canagliflozin was also associated with a lower rate of progression of albuminuria; however, amputation occurred more frequently.

References:

Neal B, Perkovic V, Mahaffey KW, et al., on behalf of the CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017;Jun 12:[Epub ahead of print].

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Smoking

Keywords: Albuminuria, Amputation, Antihypertensive Agents, Atherosclerosis, Blood Pressure, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Cholesterol, HDL, Glucose, Lipoproteins, HDL, Metabolic Syndrome X, Myocardial Infarction, Primary Prevention, Risk Factors, Smoking, Stroke


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