New ACC Guidance on CVD Risk Reduction in Diabetes

Debra L Beck

August 05, 2020

A new expert consensus statement issued by the American College of Cardiology (ACC) guides cardiologists in the initiation and monitoring of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) to reduce cardiovascular disease (CVD) risk in their patients with diabetes.

In the past few years, several drugs from these two classes, initially approved for their effects on blood glucose, have been shown to have important effects in reducing myocardial infarction, stroke, heart failure, diabetic kidney disease, and death from CVD.

"Our hope in writing this is that by helping cardiologists understand the risks and benefits of both of these classes of medications, and how to best use them, that they will feel more comfortable adding them to their therapeutic repertoire, which will help patients live longer and feel better while doing so," said Brendan M. Everett, MD, MPH, Brigham and Women's Hospital, Boston, writing committee cochair.

CVD remains the leading cause of morbidity and mortality in patients with type 2 diabetes.

The updated guidance, officially called an "Expert Consensus Decision Pathway," is published online August 5 in the Journal of the American College of Cardiology.

The document not only carefully summarizes the CV and renal outcomes trials supporting the use of SGLT2 inhibitors and GLP-1RAs, but it also offers readers a concise graphic to use when choosing which agent to prescribe; a table outlining the doses, indications, dose modifications, contraindications, and cautions for SGLT2 inhibitors and GLP-1 receptor agonists with demonstrated cardiovascular benefit; and a concise algorithm for initiation.

"It's worth noting that we carefully specify GLP-1 receptor agonists with proven cardiovascular benefit," noted Everett, "because not all of them have proven cardiovascular benefit."

In some cases, say the authors, the discussion on how best to initiate a drug from one of these classes might be with the clinician caring for the patient's diabetes, but the point is to overcome barriers to prescribing these two classes of medications because the evidence of their benefit is just so strong.

As a family doctor who treats mostly older adults, Silvy Mathew, MD, Toronto, is fielding more requests from cardiologists who would like her to start their shared patients on an SGLT2 inhibitor or GLP-1RA.

"I hear more often in the last few years from cardiologists who want us to prescribe these drugs to their patients, mostly empagliflozin, so it's nice to see a guideline expressing what individual clinicians are already thinking and doing."

She's concerned, however, that the ACC's guidance diverges somewhat from the current diabetes guidelines.

"The ACC guidance implies that high-risk patients should be started on a SGLT2 inhibitor or a GLP-1, depending on preferences and priorities, but it's a bit confusing because the diabetes guidelines recommend metformin and comprehensive lifestyle modification for first line," said Mathew. "And I would also suggest that more clarity is needed around those with prediabetic A1c and high risk for ASCVD."

Everett acknowledged the ambiguity and suggested the discrepancy is partly intentional.

"If you look at the diabetes guidelines, first-line therapy is metformin and lifestyle modification, but below that it suggests that if there are indicators of high-risk or established ASCVD, you should consider a GLP-1 receptor agonist or an SGLT2 inhibitor, independently of baseline HbA1c," said Everett in an interview.

"So, what they're actually saying is that if your patient has atherosclerotic cardiovascular disease, think about using these drugs, regardless of what their A1c is or where your trying to get with their A1c," he added.

"An important paradigm shift in the care of patients with diabetes and cardiovascular disease is underway," said Sandeep R. Das, MD, MPH, cochair of the writing committee. "Patients and physicians can now choose from a number of medications that have important proven benefits on cardiovascular and renal outcomes, in addition to their effects on blood glucose."

EMPEROR-Reduced Top-Line Results Released

These new guidelines come on the heels of an announcement from Boehringer Ingelheim and Eli Lilly and Company that treatment with their SGLT2 inhibitor, empagliflozin 10 mg (Jardiance), added to standard care significantly reduced the risk for cardiovascular death or heart failure hospitalization in patients with heart failure with reduced ejection fraction (HFrEF), with and without diabetes.

Empagliflozin is an SGLT2 inhibitor used to treat type 2 diabetes.

These top-line result were released in a company press release ahead of the presentation of the full results of the phase 3 EMPEROR-Reduced trial, scheduled for August 29, the first day of the European Society of Cardiology (ESC) Congress 2020, The Digital Experience.

The US Food and Drug Administration gave dapagliflozin an approved indication for HFrEF in May, on the basis of findings from the DAPA-HF trial. A regulatory submission for empagliflozin is planned for later in 2020, according to company press release.

A second trial of empagliflozin, EMPEROR-Preserved, is exploring the effect of the drug on cardiovascular death or hospitalization in adults with heart failure with preserved ejection fraction (HFpEF). Initial results are expected in 2021.

Neither of the writing committee cochairs, Everett and Das, have any financial conflicts of interest to report. Mathew also reported no financial conflict of interest.

J Am Coll Cardiol. Published online August 5, 2020. Abstract

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