Patients at High Risk for Cardiovascular Events Benefit from Intensive Cholesterol-Lowering Targets

An open-label trial enrolling South Korean patients with elevated cardiovascular risk showed that using low-density lipoprotein cholesterol (LDL-C) targets below 55 mg/dL significantly reduced the risk for major adverse cardiovascular events (MACE) over 3 years compared with the use of less stringent goals. Byeong-Keuk Kim, MD, Professor in the Division of Cardiology at Yonsei University, in Seoul, South Korea, presented data on cardiovascular outcomes from the Ez-PAVE trial at the 75th Annual Scientific Session of the American College of Cardiology, in New Orleans. 

An LDL-C target below 55 mg/dL is recommended for patients at very high risk for cardiovascular events, such as those with atherosclerotic cardiovascular disease (ASCVD), recent myocardial infarction, or a history of stroke. The updated guidelines for the management of dyslipidemia have endorsed a "lower is better" approach aimed at reducing residual risk and preventing secondary events in this vulnerable population. 

The Ez-PAVE trial included 3,048 patients with ASCVD with a mean age of 64 years. Approximately half of the participants were assigned to the intensive-targeting group (LDL-C targets below 55 mg/dL) while the other half were assigned to the conventional-targeting group (LDL-C targets below 70 mg/dL). Individuals who were assigned to more intensive targets had lower median LDL-C levels (56 mg/dL) during the study period than those who were assigned to less intensive LDL-C targets (66 mg/dL). The intensive-targeting group also had a lower incidence of MACE (6.6%) over 3 years of follow-up compared with the other group (9.7%). 

“Cardiovascular death rates were not significantly different [between the groups],” Kim said. “However, nonfatal myocardial infarction occurred significantly less frequently in the intensive targeting group than in the conventional targeting group (0.8% vs 1.7%) and revascularization was also reduced in the intensive targeting group.” Kim noted that more than one-third of the patients who were managed with intensive cholesterol-lowering strategies did not reach LDL-C targets below 55 mg/dL at 3 years, an effect that may be attributed to the limited use of add-on non-statin therapies in this population. 

Patients who were managed with intensive lipid-lowering strategies did not experience higher rates of treatment-related adverse events than their counterparts who were managed conservatively. There were no significant differences between the groups in terms of new-onset diabetes, worsening of glycemic control, statin-associated muscle symptoms, cancer diagnosis, cataract surgery, or elevations in liver and muscle enzymes. “Interestingly, [the incidence of] creatinine elevation was lower in the intensive-targeting group,” Kim remarked. 

Despite the relatively short follow-up period and the focus on an East Asian population, the Ez-PAVE trial provided valuable information for clinicians looking to optimize cholesterol management strategies for their patients at high risk. “In the Ez-PAVE trial, involving patients with ASCVD, intensive LDL cholesterol targeting resulted in a lower 3-year risk of cardiovascular events than conventional targeting,” Kim concluded. “These findings provide randomized evidence supporting more intensive lipid-lowering strategies for secondary prevention, consistent with current guideline recommendations.” 

Session moderator Christie Ballantyne, MD, Chief of Cardiology and Cardiovascular Research at the Baylor College of Medicine in Houston, Texas, noted that the trial provided important safety data that can guide clinical decision-making. “There are a lot of concerns, particularly in our Asian patients, about hemorrhagic stroke and diabetes,” Ballantyne said. “[In this trial], there was no increase in stroke and no problems in terms of diabetes. [These are] very important findings for the implementation in clinical practice.”