PracticeUpdate Cardiology March 2019

EXPERT OPINION 17

back into the EMPA-REG-OUTCOME data- base to look at amputations and we could find no effect to increase the risk in our study with empagliflozin so it appears to date to be specific to canagliflozin and the reason for that, the reason for these differ- ences is not entirely known. What is the impact of empagliflozin on risk of CV death and heart failure hospitalization for patients at low versus high heart failure risk? Dr. Inzucchi: Well, we’ve looked at this question. Remember that in EMPA- REG-OUTCOME all of our patients had established cardiovascular disease so they’re all at high risk but we used a health ABC heart failure risk score to further dis- tinguish our patients into low, moderate, or high heart failure risk and interestingly the drug prevented heart failure hospi- talization and cardiovascular mortality in each of these groups and there was no heterogeneity so this may be pushing the envelope a little bit, but it seems that the drug not only prevents the progression of

I think what’s important to know is that in those patients with mild to moderate CKD the drug is very effective in slowing that progression. In fact, there is several clinical trials now under way specifically testing this notion and these trials interestingly enough are including both patients with and those without type 2 diabetes. So I think within a few short years we’ll know whether this drug class is important in those patients with CKD, again with and without diabetes. What data do we have regarding the associ- ation of some SGLT2 inhibitors (canagliflozin) with an increased risk of lower limb amputa- tions vs other SGLT2 inhibitors? Dr. Inzucchi: Well, to date the only clinical trial that has reported that has shown an increase in amputation rates has been CANVAS with canagliflozin. There was a doubling of the risk. The reason for this is not clear. It tended to occur in patients who already had advanced peripheral vascular disease and particularly in those patients that already had had amputations, we went

heart failure but might also prevent heart failure from developing to begin with. Are these effects dose-dependent? Dr. Inzucchi: We did not find any dose dependency on any of the outcomes in EMPA-REG-OUTCOME so cardiovascular mortality, heart failure hospitalization, pro- gression of CKD was seen equally in both the 10 and the 25 mg dose. How do you use SGLT2 inhibitors in your practice? Dr. Inzucchi: Well, I usually follow the guide- lines so we’re using SGLT2 inhibitors not as monotherapy. We almost always start with metformin but it’s a good add-on drug after metformin, especially in those patients that have cardiovascular disease and I tend to favor them over GLP-1 receptor agonists in those patients who are either at risk for heart failure or already have heart failure. www.practiceupdate.com/c/70057

VOL. 4 • NO. 1 • 2019