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)

Primary versus secondary prevention: Approximately 34% of the cohort was enrolled for primary prevention (age ≥50 years, no known coronary artery disease/ cardiovascular disease/ peripheral artery disease, at least two risk factors). Event rates were higher in the secondary prevention subset. Compared with placebo, canagliflozin reduced the primary endpoint (p for interaction = 0.18), heart failure hospitalization (p for interaction = 0.91), and progression to albuminuria (p for interaction = 0.48) in both subgroups. It also increased lower extremity amputations (p for interaction = 0.63) in both subgroups.

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. Effects were similar among both primary and secondary prevention participants, with lower event rates among the primary prevention participants.

References:

Mahaffey KW, Neal B, Perkovic V, et al., on behalf of the CANVAS Program Collaborative Group. Canagliflozin for Primary and Secondary Prevention of Cardiovascular Events: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study). Circulation 2017;Nov 13:[Epub ahead of print].

Presented by Dr. Kenneth W. Mahaffey at the American Heart Association Annual Scientific Sessions (AHA 2017), Anaheim, CA, November 13, 2017.

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;377:644-57.

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

Keywords: AHA17, AHA Annual Scientific Sessions, 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, Secondary Prevention, Smoking, Stroke


< Back to Listings