Highlighting Treatment Gaps, the Potential of Combination Therapy in Cholesterol Management

Ez-PAVE was conducted exclusively in South Korea, and the trial's treatment environment differed from US practice in notable ways. PCSK9 inhibitor use was minimal—approximately 2%—because reimbursement and access constraints limited their availability at the time. Bempedoic acid was similarly unavailable. Yet ezetimibe use reached approximately 28%, substantially higher than typical US rates—a finding that underscores ezetimibe's underutilization in American practice despite a decades-long safety record and strong outcome data.

Even within this combination-friendly context, only 61% of patients in the intensive arm reached the below-55 mg/dL target 3 years. This is a powerful reminder that achieving guideline-recommended goals requires maximizing the full toolkit. Had PCSK9 inhibitors and bempedoic acid been broadly accessible, goal attainment rates might have been considerably higher. In the US, where these agents are available but often face prior authorization hurdles, the practical barrier is not scientific—it is systemic.

Regarding generalizability, the findings are reassuring rather than limiting. Populations of Asian descent often experience more statin-related muscle symptoms, yet fewer than 3% of participants in the intensive arm discontinued or reduced their statin dose due to adverse effects—and no excess in new-onset diabetes or worsening glycemic control was observed. This challenges the perception, prevalent in observational literature, that statin side effects are highly common; trial data consistently suggest that many reported symptoms reflect a nocebo effect rather than true pharmacologic harm. The RACING trial further supports combination therapy in this population. Taken together, the data from South Korea reinforce principles—lower is better, combination therapy is essential, and intensive LDL lowering is safe—that are fully applicable in Western clinical settings.