Patients with Cardiovascular Disease and Diabetes Benefit from Intensive Lipid-Lowering Strategies

Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels may significantly decrease risk for cardiovascular events for individuals with atherosclerotic cardiovascular disease (ASCVD) and diabetes, according to real-world data presented at the 75th Annual Scientific Session of the American College of Cardiology, in New Orleans.

 
Multisociety guidelines recommend maintaining low LDL-C levels, typically below 55 mg/dL, for patients with diabetes, who are at a high risk for adverse cardiovascular events. Despite these recommendations, real-world data have shown that many individuals with diabetes have cholesterol levels above these targets. An analysis of claims from a database linked to electronic health records was designed to estimate the effect of LDL-C reduction on the risk of hospitalization for myocardial infarction or stroke within 12 months after a diagnosis of ASCVD among patients with diabetes. The study included more than 32,000 patients with a mean age of 61 years who experienced a cardiovascular event between January 2007 and September 2023. All participants had diabetes, defined by the presence of at least one inpatient or two outpatient diabetes diagnosis codes, and LDL-C levels equal to or higher than 70 mg/dL. 

A machine learning-based model was used to analyze the causal relationship between LDL-C levels and hospitalization for subsequent ASCVD events within 12 months of a first ASCVD event. ASCVD events included peripheral arterial disease (29%), stable angina (22%), acute coronary syndrome (17%), ischemic stroke (12%), coronary revascularization (11.5%), and transient ischemic attack (8%). Hypertension was a common comorbidity in this population, along with chronic kidney disease and heart failure. 

“Over half of the population had baseline LDL-C levels of 100 mg/dL or higher,” said presenting author Nafeesa Dhalwani, PhD, director of observational research at Amgen. “At follow-up, the median LDL-C level was 81 mg/dL, but two-thirds of this population was still over the target of 70 mg/dL.” The study showed that 35% of the patients with diabetes and LDL cholesterol levels above 70 mg/dL were not on lipid-lowering therapies at baseline, and approximately 25% were still not receiving lipid-lowering therapies in the follow-up period. The use of low- to moderate-intensity statins was stable between the two period, while the use of high-intensity statin therapy increased during the follow-up. However, the proportions of patients who used ezetimibe and other non-statin therapies were consistently low.  

Patients who achieved lower LDL-C targets (<55 mg/dL) experienced a greater reduction in cardiovascular risk than those who achieved LDL-C levels below 70 mg/dL. The benefit was also greater for patients with higher baseline LDL-C levels. 

“Our findings are in line with the guidelines that have just been released, showing that intensive LDL-C control to less than 70 mg/dL for high-risk patients and to less than 55 mg/dL for very high-risk patients leads to substantial reductions in cardiovascular risk,” Dhalwani said. “These analyses are limited to 12 months. As we go longer in the follow-up, we may see more pronounced reductions.”   

These real-world data reinforce the benefit of using lower goals for LDL-C reduction in patients with ASCVD and diabetes, the speaker said. However, significant barriers remain to the implementation of these goals in clinical practice. “Polypharmacy is a real issue, but so is [the impact of] cholesterol,” Dhalwani added. “Often, when we are in situations where patients have diabetes and high cholesterol, somehow, A1c or blood pressure are managed but LDL-C is often ignored. That is a mindset that can change. In clinical practice, we need to recognize that treating one risk factor is not enough, that we have to manage all of them together, including LDL cholesterol.”