Ez-PAVE tested whether people with established cardiovascular disease benefit from a more aggressive LDL cholesterol goal. Participants were assigned to a target below 55 mg/dL or below 70 mg/dL and followed for three years. The combined rate of cardiovascular events - including cardiovascular death, heart attack, stroke, procedures to restore blood flow, and hospitalization for unstable angina - was 6.6% in the lower-target group, compared with 9.7% in the standard-target group, a 33% relative reduction. Fewer heart attacks and procedures accounted for much of the difference; the trial did not demonstrate fewer cardiovascular deaths. The result is notable because only about 61% of the intensive group reached the lower target.
Doctors used more high-intensity statins and combinations of statins with ezetimibe in the intensive group; by year three, median LDL was 52 mg/dL versus 66 mg/dL. Limited insurance coverage and availability of newer drugs, including PCSK9 inhibitors, impeded treatment. The trial found no significant differences in new diabetes, treatment-changing muscle symptoms, liver enzyme elevations, or cancer, though it cannot rule out rare or long-term harms. Genetic studies suggest lifelong very low LDL can accompany low heart-disease risk, but they do not establish a safe or optimal lower limit for medication. For people with cardiovascular disease, the findings support discussing an LDL goal below 55 mg/dL with a clinician, while choosing treatment based on tolerance and medical history.
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