Cardiometabolic risk

Brendan M. Everett, MD, MPH, on Anti-Inflammatory Therapy for CVD and Diabetes

Inflammation is common among individuals with cardiovascular disease (CVD) and diabetes. But do you know which anti-inflammatory medications work best among this patient population? Cardiology Consultant caught up with Dr Brendan Everett after he presented “Anti-Inflammatory Therapy for CVD & Diabetes” at the World Congress Insulin Resistance Diabetes & Cardiovascular Disease conference.

Brendan M. Everett, MD, MPH, is the Director of General Cardiology Inpatient Service at Brigham and Women’s Hospital and is an Assistant Professor at Harvard Medical School in Boston, Massachusetts.

Cardiology Consultant: Which anti-inflammatory medications are effective and safe for patients with comorbid CVD and diabetes?

Brendan Everett: At present, the best and most effective anti-inflammatory medications for patients with diabetes and ASCVD are statins. For patients with diabetes, statins have years of demonstrated efficacy in preventing heart attack, stroke, and cardiovascular death. They are also remarkably safe. At present, no other anti-inflammatory medications to treat ASCVD in patients with diabetes are available, although some, such as colchicine, are being tested in large randomized trials. 

CARDIO CON: You were a lead researcher for the CANTOS trial. Can you tell us more about that trial and its conclusions?

BE: CANTOS was a large, randomized trial of the IL-1ß inhibitor canakinumab in patients with a prior heart attack and a high-sensitivity C-reactive protein ≥2 mg/L. Over a median 3.7 years of follow up, IL-1ß inhibition with canakinumab 150 mg or 300 mg given subcutaneously every 3 months led to 15% relative risk reduction in heart attack, stroke, or cardiovascular death.

There was also a 17% relative risk reduction in the secondary endpoint of heart attack, stroke, unstable angina requiring unplanned coronary revascularization, or cardiovascular death. However, canakinumab has not been approved by the US Food and Drug Administration for the prevention of major adverse cardiovascular events. 

CARDIO CON: How have the conclusions from the CANTOS trial influenced the treatment regimens for patients with comorbid CVD and diabetes?

BE: In CANTOS, canakinumab was equally effective in preventing major cardiovascular events in patients with normal glucose, with prediabetes, and with established diabetes. We also were able to test whether IL-1ß inhibition reduced HbA1c concentrations in patients with prediabetes and whether it delayed the progression from prediabetes to diabetes. We found a statistically significant, dose-dependent reduction in HbA1c for the first 9 to 12 months of randomly allocated canakinumab therapy but did not see any statistically significant evidence that canakinumab delayed the progression from prediabetes to diabetes.

Finally, in an exploratory analysis of the CANTOS data, we reported evidence that IL-1ß inhibition was associated with a dose-related reduction in heart failure hospitalization and heart failure-related mortality. This is the first large-scale study to demonstrate that an anti-inflammatory therapy can reduce these events, which are increasingly common in patients with ASCVD and diabetes. These data suggest that a novel therapeutic pathway of inflammation reduction may offer benefit for patients at risk for heart failure, if our results are validated in other studies.

However, as noted previously, no anti-inflammatory medications aside from statins are readily available. However, we believe that the results of CANTOS will prompt further drug development and evaluation in the treatment of inflammation as a means to prevent major cardiovascular events.