PARIS — The European Society of Cardiology (ESC) in collaboration with the European Association for the Study of Diabetes (EASD) has released new guidelines for the management and prevention of cardiovascular disease (CVD) in patients with diabetes or prediabetes.
Recommendations in the document reflect recent positive findings from large cardiovascular outcome trials (CVOTs) of new classes of diabetes drugs and other new developments.
The guideline updates the 2013 version: It not only provides advice about new classes of diabetes drugs based on groundbreaking CVOTs but also removes metformin from its place as initial diabetes therapy for all. They further stratify CV risk into medium-, high-, and very-high-risk levels rather than primary prevention and secondary prevention.
The document reflects "an unprecedented increase in the evidence base available for practicing healthcare professionals to refer to in their daily consultations," write Francesco Cosentino, MD, PhD, Karolinska Institute and Karolinska University Hospital in Stockholm, Sweden, and Peter J. Grant, MD, University of Leeds, United Kingdom, respective ESC and EASD co-chair chairs of the writing task force.
Cosentino and Grant presented the guidelines here at the ESC Congress 2019, and the document was simultaneously published online August 31 in European Heart Journal and on the ESC website.
"The last 5 years has been the most exciting time in diabetes research ever," said Cosentino, "since for the first time in the history of type 2 diabetes, we have data from several CVOTs that indicate CV benefits from the use of glucose-lowering drugs in patients with CVD or at very high/high CV risk."
The guidelines incorporate evidence that has emerged from the trials of sodium-glucose co-transporter-2 (SGLT2) inhibitors — the EMPA-REG OUTCOME trial of empagliflozin (Jardiance, Boehringer Ingelheim/Lilly), the CANVAS trial of canagliflozin (Invokana, Janssen), and the DECLARETIMI 58 trial of dapagliflozin (Farxiga/Forxiga, AstraZeneca) — and from glucagon-like peptide-1 (GLP-1) receptor agonists: notably the LEADER trial of liraglutide (Victoza, Novo Nordisk), the SUSTAIN-6 trial of semaglutide, the Harmony Outcomes trial of albiglutide, the REWIND trial of dulaglutide (Trulicity, Lilly), and the PIONEER 6 trial of semaglutide.
"A key starting point of our guidelines," said Cosentino, is the reclassification of CV risk in patients with diabetes based on comorbidities and duration of disease, rather than just lumping them as needing primary or secondary prevention of CVD.
The guidelines classify patients with diabetes as follows:
Medium CV risk If they are young, lack other CV risk factors, and have had diabetes for less than 10 years;
High CV risk if they have had diabetes for more than 10 years and have at least one other risk factor, but no target-organ damage; and
Very high CV risk if they have CVD or target-organ damage or have had type 1 diabetes for more than 20 years.
Trial evidence strongly suggests that these new drugs should be recommended for patients with type 2 diabetes and prevalent CVD or very high/high CV risk, such as those with target-organ damage or several CV risk factors, whether they are treatment naive or already receiving metformin.
"We are really facing a major paradigm shift" in the use of metformin, said Cosentino. For drug-naive patients with type 2 diabetes and established CVD, very-high-risk patients, the guideline advises immediate initiation of an SGLT-2 inhibitor or GLP-1 receptor agonist or adding this to existing metformin therapy.
"This is important," Grant told theheart.org | Medscape Cardiology in an email, "because until now, all guidelines have recommended metformin as first-line therapy in all cases of type 2 diabetes. The strength of evidence shows this is no longer the correct strategy."
The guideline also notes that the benefits seen with GLP-1 receptor agonists "are most likely derived through the reduction of arteriosclerosis-related events," while SGLT2 inhibitors seem to reduce endpoints related to heart failure.
The "huge changes in the management of diabetes in the last 5 years or so," said Grant, "is probably the greatest achievement since the discovery of insulin in 1924."
Grant drew attention to the following key updates in the current guideline iteration:
"We should no longer talk about primary and secondary prevention," he said, but instead classify patients with diabetes as having moderate, high, or very high risk for CVD.
A new aspirin CVOT (ASCEND) in moderate-risk diabetes led them not to recommend aspirin in moderate-risk patients but to use it in high- and very-high-risk patients on an individual basis.
Two trials of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors —including one with a diabetes substudy — led them to recommend PCSK9 inhibitor therapy in very-high-risk patients who have persistently high low-density lipoprotein cholesterol levels despite maximal statin and ezetimibe treatment or with statin intolerance.
The COMPASS trial of rivaroxaban plus aspirin in patients with stable coronary artery disease led to the recommendation for its use in dual antiplatelet therapy in longer-term prevention of CVD.
At the same time, "glycemic control should not be forgotten," Grant cautioned, because it helps prevent microvascular complications to the eyes, nerves, and kidneys.
The guidelines advise aiming for a hemoglobin A1c level below 7%, especially in young adults who have not had diabetes for long.
The document also recommends lipid targets of 2.5 mmol/L, 1.8 mmol/L, and less than 1.4 mmol/L for patients with diabetes who are at medium, high, and very high risk for CVD disease, respectively.
In addition, it advises that PCSK9 inhibitors are clearly needed in patients with diabetes classified as being at very high risk for CV events and that aspirin may be considered for such patients, but not for patients at moderate risk for CV events.
Invited to comment, Robert H. Eckel, MD, University of Colorado, Denver, past president of the American Heart Association (AHA, 2005 to 2006), and soon to be co-president of the American Diabetes Association (ADA, January 2020) told theheart.org | Medscape Cardiology In an email that, in general, US healthcare practitioners turn to Standards of Medical Care from the ADA/EASD for diabetes care advice and to guidelines and position statements from the AHA and American College of Cardiology for cardiology care advice.
This version of the ESC/EASD guidelines for patients with diabetes and CVD shows the importance of SGLT2 inhibitors and GLP-1 receptor agonists based on CVOTs, he said, "including placing them as primary therapy vs. metformin for patients at high or very high risk for CVD — which is a new way to classify patients instead of classifying them as patients being treated for primary prevention or secondary prevention of CVD."
The relevant financial disclosures are listed with the guidelines.
European Society of Cardiology (ESC) Congress 2019.
Eur Heart J. Published online August 31, 2019. Full text
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Cite this: ESC Diabetes and CVD Guideline: 'Unprecedented' New Evidence - Medscape - Sep 02, 2019.