Carol H. Wysham, MD


June 21, 2017

Editorial Collaboration

Medscape &

Hello. I'm Dr Carol Wysham from Spokane, Washington. I'm here today at the 77th annual American Diabetes Association meeting.

We just heard the results of the eagerly awaited CANVAS trial.[1] The CANVAS trial looked at canagliflozin versus placebo in patients at high risk for cardiovascular (CV) disease and in patients with established CV disease. The primary endpoint of three-point major adverse CV events (MACE)—nonfatal myocardial infarction, nonfatal stroke, and CV death—was statistically significantly lowered with canagliflozin compared with placebo, demonstrating about a 14% reduction in risk.

Each component of the three-point MACE showed a trend towards reduction in risk with canagliflozin versus placebo, but they were not all statistically significantly different. Specifically, there was no statistically significant reduction in CV death, but there was a very significant reduction in congestive heart failure, a secondary endpoint, with a 39% reduction in hospitalization for heart failure.

On the other side, about a doubling of toe amputations was reported, with 0.6% of patients experiencing an amputation. To put that in perspective, the rate was 3 per 1000 patient-years in the placebo group and 6 per 1000 patient-years in the treatment group.

I personally think that the results are going to show a class effect.

The reason for this is not established, but conversations with interventional cardiologists point out that it's most likely a volume depletion issue. You are bringing blood pressure down in a population that already has impaired microcirculation in their skin and nerves. In these older patients in CANVAS, the blood pressure reduction could have been as much as 7 or 8 mm Hg. Patients in my practice were actually coming out of the ACCORD trial into the CANVAS trial. Remember, there was an intensive blood pressure arm in ACCORD, and some patients' blood pressures were actually under 120 systolic.

Fractures are also likely related to volume depletion, dizziness, and falls. Fractures were not the typical osteoporotic fractures but rather in the small bones of the hand and feet.

These data are exciting. It's probably a little too soon to say that it is a class effect. There are primary and secondary prevention arms in these studies, and all we have are the combined data. We really need subanalyses to see what [happens] in EMPA-REG-like patients, meaning those with established CV disease.

I personally think that the results are going to show a class effect. Importantly, I think even the adverse events are going to be a class effect as well, and I think they are preventable. We just need more data.

We need to lower blood pressure medications in patients who are already at goal and make sure that patients understand the importance of good hydration, which is very important to avoid volume depletion, especially in that first week after starting canagliflozin.

I want to thank you for your attention and for listening to this update on the CANVAS trial.


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