ACR CONVERGNCE 2021—Controlling inflammation—in addition to lowering cholesterol levels and other strategies—is an increasingly recognized component of managing cardiovascular (CV) risk. Also, targeting changes to the function and structure of high-density lipoprotein (HDL) in the setting of inflammation may improve CV outcomes for people with rheumatic disease. Speakers at ACR Convergence 2021 offered these insights and more in a session that explored how to manage risk and outcomes related to cardiovascular disease.
Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital, Boston, and associate professor of medicine at Harvard Medical School, offered a cardiologist’s perspective during the presentation. When it comes to low-density lipoprotein (LDL) levels, the field has gone from “lower is better” to “lowest is best,” according to Dr. Plutzky, especially with regard to patients reaching a certain level of CV risk.
“Cardiologists’ broad view is that this is an incredibly common problem, that patients go through a very long preclinical phase before CV complications of atherosclerosis are manifest[ed], and that provides an opportunity to intervene during those early phases,” he said. “Many aspects of cardiovascular risk are modifiable and that represents a chance to avoid some chronic sequelae and even some particularly adverse outcomes, like CV death.”
Efforts to get LDL lower and lower are seen in recent therapy development beyond statins. Example: Inclisiran—approved in Europe and under review in the U.S.—uses small interference RNA to target production of proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that degrades LDL receptors and leads to higher LDL levels. Alirocumab and evolucumab, which also target PCSK9, have shown positive effects in clinical trials when they are added to statin therapy.1,2
In another study, a specific type of omega-3 fatty acid, icosapent ethyl, was found to have a “striking benefit” when added to statin therapy in patients with high CV risk.3 Questions have been raised about the placebo used in the study, but Dr. Plutzky noted the 25% risk reduction suggests the benefit is likely real.
Bempedoic acid, alone or with ezetimibe, reduces LDL, as well as C-reactive protein levels, raising “an intriguing question” for rheumatologists.4 “Is there an anti-inflammatory effect here and may that contribute to benefits in the clinical trial? We’ll have to wait and see,” said Dr. Plutzky. Results from a phase 3 study are expected in spring 2022.
Canakinumab, an antibody to interleukin (IL) 1b, produced reductions in inflammation and CV events, but no change in LDL.5 “One can point to this as a proof of concept that inflammation matters. Whether this is a therapy for cardiovascular disease isn’t clear, but it highlights important issues,” Dr. Plutzky said.