Prakash C. Deedwania
CHICAGO — Although recent trials indicate intensive lipid-lowering therapy is advantageous for patients with diabetes, specific LDL targets remain elusive, according to a presentation at the American Heart Association Scientific Sessions.
“Available data do suggest that due to the heightened risk, intensive lipid-lowering therapy in diabetic patients appears to be beneficial — lower LDL is better — but the need for a specific target LDL level that we can recommend with confidence requires confirmation in prospective randomized control trials, which we are probably not going to see,” Prakash C. Deedwania, MD, FACC, FACP, FAHA, professor of medicine and director of cardiovascular research at UCSF School of Medicine, said during his presentation.
CVD is the leading cause of death among patients with diabetes. Because CVD, particularly CAD, has been linked to LDL, guidelines from the American Heart Association, American College of Cardiology and 10 other societies recommend moderate-intensity statin therapy to lower LDL among various groups of patients, including those with diabetes and an LDL of at least 70 mg/dL.
“Diabetic patients are at heightened risk of CV events over non-diabetics,” Deedwania said. “LDL-C modification with statins, PCSK9 inhibition or ezetimibe could be of benefit.”
He cited results from the Cholesterol Treatment Trialists’ Collaboration, which showed statin therapy reduced the relative risk for major vascular events in patients with type 2 diabetes. He also discussed findings from the CARDS trial, which was prematurely terminated after researchers observed a statistically significant reduction of 37% in major CV events among patients with diabetes who received 10 mg of atorvastatin vs. placebo. In addition, stroke reduction was nearly 50% in the statin arm of the study.
In the TNT study, which compared the effects of an 80-mg dose of atorvastatin vs. a 10-mg dose of atorvastatin in patients with diabetes, those who received the higher statin dose had a 25% lower risk for major CV events. Further, the IMPROVE-IT trial showed that the addition of ezetimibe (Zetia, Merck) to simvastatin (Zocor, Merck) was associated with a greater reduction in a combined endpoint of stroke and MI in patients with diabetes (14%) than patients without diabetes.
“Ezetimibe vs. placebo in nondiabetic patients was a wash,” Deedwania said. “I don’t see the basis for recommending ezetimibe across the board as a second-line therapy for secondary prevention.”
While there have been concerns about an increase in new-onset diabetes with statin use, Deedwania said the benefit is far greater. He reported that a safety and efficacy study of the PCSK9 inhibitor evolocumab (Repatha, Amgen) showed a “dramatic reduction” in LDL with the treatment, which was similar in patients with diabetes vs. those without diabetes. In addition, there were no significant adverse events other than injection site reaction. An examination of glycose parameters, HbA1c and fasting plasma glucose, showed no change in patients with diabetes vs. those without diabetes at baseline.
“So, I think if you want to go to intensive lipid-lowering therapy but you may be a little bit concerned about statins inducing glucose intolerance, certainly, PCSK9 [inhibition is] a good alternative,” Deedwania said.
New data from the REDUCE-IT trial showed 2 g of icosapent ethyl (Vascepa, Amarin Pharmaceuticals), a pharmaceutical-grade omega-3 fatty acid, given twice daily was superior to placebo in reducing the risk for ischemic events among patients with established CVD or diabetes (plus other risk factors) and elevated triglycerides, despite statin therapy.
Although the American Association of Clinical Endocrinologists (AACE) recommends an LDL treatment target of less than 55 mg/dL for an “extreme-risk group” of patients with diabetes who have progressive ASCVD and established CVD, along with heterozygous familial hypercholesterolemia or stage 3 or 4 CKD, and a target goal of less than 70 mg/dL for a “very high-risk group” of patients with vascular disease, diabetes or stage 3/4 CKD, and heterozygous familial hypercholesterolemia, Deedwania said more research is needed to confirm an optimal LDL target. – by Gina Brockenbrough, MA
Deedwania PC. Intensive lipid-lowering therapy in diabetes: How low should we go? Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.
Disclosure: Deedwania reports being a consultant or advisor for Amgen, Esperion and Sanofi Pasteur.