New insights on diabetes, CVD research from the TIMI Study Group
LOS ANGELES — In a presentation at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease, speakers highlighted recent data from the TIMI Study Group on treatment options for diabetes and CVD.
The talks focused on an oral anticoagulant in patients with diabetes and atrial fibrillation, CV outcomes with an obesity drug, CV effects of an SGLT2 inhibitor and new PCSK9 inhibitor data.
ENGAGE AF-TIMI 48
As previously reported by Healio, the ENGAGE AF-TIMI 48 trial evaluated outcomes with the novel oral anticoagulant edoxaban (Savaysa, Daiichi Sankyo) compared with warfarin in patients with AF. In the overall trial, edoxaban significantly reduced CV death, major bleeding and net outcomes. Additional analyses also showed reduced risk for stroke compared with warfarin and improved clinical outcomes in specific AF subtypes.
At WCIRDC, Anna Plitt, MD, an internist at Mount Sinai Medical Center, discussed a meta-analysis published in 2018 that looked at outcomes with edoxaban vs. warfarin in patients with diabetes and AF. Results showed adjusted rates of bleeding, thromboembolic events and mortality were highest among patients with insulin-dependent diabetes and were moderately increased in patients with noninsulin-dependent diabetes when compared with those who did not have diabetes.
“Since patients with diabetes and AF are at increased risk of adverse outcomes, use of safer and more effective [newer oral anticoagulants] such as edoxaban may be preferred over the use of vitamin K antagonists,” Plitt said here. “The meta-analysis suggests that important differences may exist between the [newer oral anticoagulants], and head-to-head randomized controlled trials are needed in patients with both conditions, diabetes and atrial fibrillation.”
In the CAMELLIA-TIMI 61 trial, treatment with the serotonin receptor agonist lorcaserin (Belviq, Eisai) yielded sustained weight loss during a median follow-up of 3 years, without excess risk for major adverse CV events in adults with overweight or obesity at high risk for CV events. The trial enrolled patients with a BMI of at least 27 kg/m² (median, 35 kg/m²) and established atherosclerotic CVD or multiple CV risk factors. Nearly 57% presented with diabetes and 75% established atherosclerotic CVD.
“It has yet to be determined whether we can improve cardiovascular outcomes in these patients,” Erin Bohula May, MD, DPhil, associate physician at Brigham and Women’s Hospital, instructor at Harvard Medical School and investigator with the TIMI Study Group, said during her presentation. “I do think we probably will see it eventually. As we know, diet and exercise are the cornerstone of chronic weight management in these patients. I believe that bariatric surgery, while it’s effective and durable, will ultimately be beneficial from a cardiovascular standpoint, but that data has yet to be produced. Ultimately, the pharmacologic agents certainly result in weight loss. It is variable depending on the agent. They definitely improve cardiometabolic parameters, and we have yet to see cardiovascular benefit from this class of medications.”
The DECLARE-TIMI 58 trial of dapagliflozin (Farxiga, AstraZeneca) in patients with type 2 diabetes who had or were at high risk for ASCVD adds to the growing body of evidence demonstrating the favorable effects of SGLT2 inhibitors on CV risk. Previously reported data showed significant relative risk reduction in the coprimary efficacy endpoint of CV death or HF hospitalization among those treated with dapagliflozin vs. placebo.
“This had led to both guideline updates and regulatory approvals around the world,” Stephen D. Wiviott, MD, executive director of the clinical trials office at Partners HealthCare, senior investigator with the TIMI Study Group, cardiovascular medicine specialist at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, said during the presentation. “Subsequent work is focused on key outcomes in populations at risk.”
More recent data, presented at the American Diabetes Association Scientific Sessions in June, demonstrated dapagliflozin may also offer adults with type 2 diabetes the potential to prevent and treat kidney disease. Read more here.
FOURIER , VESALIUS-CV
Robert P. Giugliano, MD, MSc, senior investigator with the TIMI Study Group, discussed recent data showing benefits of the PCSK9 inhibitor evolocumab in patients with diabetes, from secondary prevention of CV events to primary prevention.
In the overall FOURIER trial, reduction of LDL to a median of 30 mg/dL with evolocumab (Repatha, Amgen) in patients with ASCVD was associated with lower risk for CV events. Read Healio’s previous coverage of the FOURIER trial here.
Giugliano discussed a diabetes substudy that investigated the efficacy of evolocumab in patients with and without diabetes at baseline and the safety profile, particularly with respect to glycemia and the development of new-onset diabetes.
“We found that the PCSK9 inhibitor evolocumab was efficacious in patients with stable atherosclerosis whether they had diabetes or metabolic syndrome, one, the other or both, and to a greater degree it appeared in patients who had neither diabetes nor metabolic syndrome,” Giugliano, who is also associate professor of medicine at Harvard Medical School and cardiovascular medicine specialist at Brigham and Women’s Hospital, said during his presentation.
The ongoing VESALIUS-CV trial is evaluating evolocumab in patients with atherosclerosis or diabetes, but no history of MI or stroke. The randomized, double-blind trial will compare evolocumab vs. placebo for the dual primary composite endpoints of CHD death, MI or ischemic stroke and CHD death, MI, ischemic stroke or ischemia-driven revascularization.
Bohula May EA.
Wiviott SD. The TIMI Group at WCIRDC. All presented at: World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease; Dec. 4-7, 2019; Los Angeles.
Disclosures: Bohula May reports she received research grants to her institution from Amgen, AstraZeneca, Eisai, The Medicines Company, Merck and Novartis; honoraria for CME programs from Medscape, Merck and Servier, and consults for Daiichi Sankyo, Kowa, Lexicon, Merck, NIH, Novartis, Novo Nordisk and Servier. Wiviott reports his spouse is an employee of Merck; he has received research grants from Amgen, Arena, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Eisai, Janssen, Merck and Sanofi Aventis; he is a consultant or on the advisory board for Aegerion, Allergan, Amgen, Angelmed, AstraZeneca, Boehringer Ingelheim, Boston Clinical Research Institute, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, ICON Clinical, Janssen, Lexicon, Merck and St. Jude Medical; and has other financial ties with Merck Research Laboratory. Giugliano reports he received research grant support through Brigham and Women’s Hospital from Amgen, Daiichi Sankyo and Merck and has other financial relationships with Akcea, Amarin, Amgen, Bristol-Myers Squibb, CVS Caremark, Daiichi Sankyo, Merck and Pfizer. Healio could not confirm relevant financial disclosures for Plitt at the time of publication.