Patients with stable coronary artery disease and type 2 diabetes mellitus could benefit from a “plethora of newly available risk-reduction strategies,” but their “adoption into clinical practice has been slow” and inconsistent, prompting an expert panel organized by the American Heart Association to collate the range of treatment recommendations now applicable to this patient population in a scientific statement released on April 13.
“There are a number of things to consider when treating patients with stable coronary artery disease [CAD] and type 2 diabetes mellitus [T2DM], with new medications and trials and data emerging. It’s difficult to keep up with all of the complexities,” which was why the Association’s Councils on Lifestyle and Cardiometabolic Health and on Clinical Cardiology put together a writing group to summarize and prioritize the range of lifestyle, medical, and interventional options that now require consideration and potential use on patients managed in routine practice, explained Suzanne V. Arnold, MD, chair of the writing group, in an interview.
The new scientific statement (Circulation. 2020 Apr 13; doi: 10.1161/CIR.0000000000000766), aimed primarily at cardiologists but also intended to inform primary care physicians, endocrinologists, and all other clinicians who deal with these patients, pulls together “everything someone needs to think about if they care for patients with CAD and T2DM,” said Deepak L. Bhatt, MD, professor of medicine at Harvard Medical School in Boston and vice chair of the statement-writing panel in an interview. “There is a lot to know,” he added.
The statement covers antithrombotic therapies; blood pressure control, with a discussion of both the appropriate pressure goal and the best drug types used to reach it; lipid management; glycemic control; lifestyle modification; weight management, including the role of bariatric surgery; and approaches to managing stable angina, both medically and with revascularization.
“The goal was to give clinicians a good sense of what new treatments they should consider” for these patients, said Dr. Bhatt, who is also director of interventional cardiovascular programs at Brigham and Women’s Hospital, also in Boston. Because of the tight associations between T2DM and cardiovascular disease in general including CAD, “cardiologists are increasingly involved in managing patients with T2DM,” he noted. The statement gives a comprehensive overview and critical assessment of the management of these patients as of the end of 2019 as a consensus from a panel of 11 experts .
The statement also stressed that “substantial portions of patients with T2DM and CAD, including those after an acute coronary syndrome, do not receive therapies with proven cardiovascular benefit, such as high-intensity statins, dual-antiplatelet therapy, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and glucose-lowering agents with proven cardiovascular benefits.
“These gaps in care highlight a critical opportunity for cardiovascular specialists to assume a more active role in the collaborative care of patients with T2DM and CAD,” the statement said. This includes “encouraging cardiologists to become more active in the selection of glucose-lowering medications” for these patients because it could “really move the needle,” said Dr. Arnold, a cardiologist with Saint Luke’s Health System in Kansas City, Mo. She was referring specifically to broader reliance on both the SGTL2 (sodium-glucose cotransporter 2) inhibitors and the GLP-1 (glucagonlike peptide-1) receptor agonists as top choices for controlling hyperglycemia. Based on recent evidence drugs in these two classes “could be considered first line for patients with T2DM and CAD, and would likely be preferred over metformin,” Dr. Arnold said in an interview. Although the statement identified the SGLT2 inhibitors as “the first drug class [for glycemic control] to show clear benefits on cardiovascular outcomes,” it does not explicitly label the class first-line and it also skirts that designation for the GLP-1 receptor agonist class, while noting that metformin “remains the drug most frequently recommended as first-line therapy in treatment guidelines.”
“I wouldn’t disagree with someone who said that SGLT2 inhibitors and GLP-1 receptor agonists are first line,” but prescribing patterns also depend on familiarity, cost, and access, noted Dr. Bhatt, which can all be issues with agents from these classes compared with metformin, a widely available generic with decades of use. “Metformin is safe and cheap, so we did not want to discount it,” said Dr. Arnold. Dr. Bhatt recently coauthored an editorial that gave an enthusiastic endorsement to using SGLT2 inhibitors in patients with diabetes (Cell Metab. 2019 Nov 5;30:47-9).
Another notable feature of the statement is the potential it assigns to bariatric surgery as a management tool with documented safety and efficacy for improving cardiovascular risk factors. However, the statement also notes that randomized trials “have thus far been inadequately powered to assess cardiovascular events and mortality, although observational studies have consistently shown cardiovascular risk reduction with such procedures.” The statement continues that despite potential cardiovascular benefits “bariatric surgery remains underused among eligible patients,” and said that surgery performed as Roux-en-Y bypass or sleeve gastrectomy “may be another effective tool for cardiovascular risk reduction in the subset of patients with obesity,” particularly patients with a body mass index of at least 35 kg/m2.
“While the percentage of patients who are optimal for bariatric surgery is not known, the most recent NHANES [National Health and Nutrition Examination Study] study showed that less than 0.5% of eligible patients underwent bariatric surgery,” Dr. Arnold noted. Bariatric surgery is “certainly not a recommendation for everyone, or even a majority of patients, but bariatric surgery should be on our radar,” for patients with CAD and T2DM, she said.
Right now, “few cardiologists think about bariatric surgery,” as a treatment option, but study results have shown that “in carefully selected patients treated by skilled surgeons at high-volume centers, patients will do better with bariatric surgery than with best medical therapy for improvements in multiple risk factors, including glycemic control,” Dr. Bhatt said in the interview. “It’s not first-line treatment, but it’s an option to consider,” he added, while also noting that bariatric surgery is most beneficial to patients relatively early in the course of T2DM, when its been in place for just a few years rather than a couple of decades.
The statement also notably included a “first-line” call out for icosapent ethyl (Vascepa), a novel agent approved in December 2019 for routine use in U.S. patients, including those with CAD and T2DM as long as their blood triglyceride level was at least 150 mg/dL. Dr. Bhatt, who led the REDUCE-IT study that was pivotal for proving the safety and efficacy of icosapent ethyl (N Engl J Med. 2019 Jan 3;380:11-22), estimated that anywhere from 15% to as many as half the patients with CAD and T2DM might have a triglyceride level that would allow them to receive icosapent ethyl. One population-based study in Canada of nearly 200,000 people with atherosclerotic cardiovascular disease found a 25% prevalence of the triglyceride level needed to qualify to receive icosapent ethyl under current labeling, he noted (Eur Heart J. 2020 Jan 1;41:86-94). However, the FDA label does not specify that triglycerides be measured when fasting, and a nonfasting level of about 150 mg/dL will likely appear for patients with fasting levels that fall as low as about 100 mg/dL, Dr. Bhatt said. He hoped that future studies will assess the efficacy of icosapent ethyl in patients with even lower triglyceride levels.
Other sections of the statement also recommend that clinicians: Target long-term dual-antiplatelet therapy to CAD and T2DM patients with additional high-risk markers such as prior MI, younger age, and tobacco use; prescribe a low-dose oral anticoagulant along with an antiplatelet drug such as aspirin for secondary-prevention patients; promote a blood pressure target of less than 140/90 mm Hg for all CAD and T2DM patients and apply a goal of less than 130/80 mm Hg in higher-risk patients such as blacks, Asians, and those with cerebrovascular disease; and reassure patients that “despite a modest increase in blood sugars, the risk-benefit ratio is clearly in favor of administering statins to people with T2DM and CAD.”
Dr. Arnold had no disclosures. Dr. Bhatt has been an adviser to Cardax, Cereno Scientific, Medscape Cardiology, PhaseBio; PLx Pharma, and Regado Biosciences, and he has received research funding from numerous companies including Amarin, the company that markets icosapent ethyl.