Residual CVD risk varies; individualized treatments best to combat it
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BOSTON — The medical community is better equipped to combat residual CVD risk than previously, but prevention of residual risk should be tailored using a precision medicine approach, a speaker said at the Cardiometabolic Health Congress.
Although statin therapy lowers CVD risk due to hyperlipidemia, “events still occur on statin medications,” Cardiology Today Editorial Board Member Erin D. Michos, MD, MHS, FACC, FAHA, FASE, FASPC, said during a presentation. “Residual risk is what this has been called. Even in the FOURIER trial, which had very impressive lipid lowering, in many cases to LDL less than 20 mg/dL, there were still events happening.”
Residual risk can be related to cholesterol that is still suboptimally controlled, lipoprotein(a), triglycerides, thrombotic factors, inflammation and diabetes, Michos said.
For cholesterol-related risk, clinicians can add nonstatin therapies such as ezetimibe or PCSK9 inhibitors to statin therapy, she said, noting that the GOULD registry has shown that many patients with atherosclerotic CVD have suboptimal LDL control but are not receiving intensified lipid-lowering therapy.
There are no therapies approved specifically for Lp(a) reduction, but a subanalysis of FOURIER found the treatment effect of evolocumab (Repatha, Amgen) was greater in patients with elevated Lp(a) compared with those with lower Lp(a), she said.
For patients with elevated triglyceride levels, icosapent ethyl (Vascepa, Amarin), a pharmaceutical-grade omega-3 fatty acid, further reduced CVD risk in patients already on statin therapy, Michos said.
For patients with residual thrombotic risk, ticagrelor (Brilinta, AstraZeneca) has been shown to be effective in patients with MI or stable CAD, and a regimen of low-dose rivaroxaban (Xarelto, Janssen/Bayer) plus aspirin reduced ischemic events in patients with stable CAD or peripheral artery disease, albeit at a cost of increased bleeding risk, Michos said.
Patients post MI with residual inflammation risk, defined as high-sensitivity C-reactive protein of 2 mg/L or more, had been shown to benefit from canakinumab, an interleukin-1-beta inhibitor, but this agent is not FDA-approved for this indication. Colchicine has been demonstrated to show benefit in patients with chronic coronary disease, but colchicine is contraindicated in many patients with chronic kidney disease. Thus, an alternative may be ziltivekimab (Novo Nordisk), a novel interleukin-6 ligand inhibitor, which was shown in the RESCUE trial to reduce hsCRP, she said, noting that the ZEUS CV outcomes trial will determine whether ziltivekimab can reduce CV events in patients with chronic kidney disease and high CVD risk.
For patients with diabetes-related residual risk, SGLT2 inhibitors have been shown to reduce CV death, HF hospitalization and progression of kidney disease, whereas GLP-1 receptor agonists have been shown to reduce major adverse CV events, CV death, MI and stroke, Michos said, noting that the SURPASS-CVOT trial of tirzepatide (Mounjaro, Eli Lilly), a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonist for reduction of major adverse CV events in people with type 2 diabetes, is ongoing.
“One size does not fit all,” Michos said during the presentation. “After the foundation of lifestyle and statins, which are background therapies in all these patients, a tailored approach using a precision medicine approach is valuable for reducing residual risk.”
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Michos ED. Defining and quantifying residual ASCVD risk in 2022. Presented at: Cardiometabolic Health Congress; Oct. 19-22, 2022; Boston.
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