The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial: to believe or not to believe?

T a I i w w l a M s p n ( 8 u t a v The beneficial effect of lowering low-density lipoprotein cholesterol (LDL-C) in clinical trials (1) has transformed our ability to reduce cardiovascular risk. However, increasing recognition that many patients experience a clinical event, despite the use of LDL-C lowering therapies, has stimulated the ongoing search to develop additional therapeutic strategies. Although elevated levels of triglycerides and lipoprotein(a) independently predict cardiovascular events (2,3), to the author’s knowledge, no clinical trial to date has demonstrated that any therapy that specifically targets either of these factors is associated with cardiovascular benefit. High-density lipoprotein cholesterol (HDL-C) has received considerable interest with respect to potential cardiovascular protection. Population studies consistently demonstrate an inverse relationship between HDL-C levels and prospective cardiovascular risk (4), which has prompted the concept that substantially increasing HDL-C would be beneficial. Preclinical studies demonstrating favorable effects of HDL-C–based interventions in cellular and animal models provide further support for the interest in developing therapies that increase HDL-C (5). However, current lipid-modifying approaches typically have modest effects on HDL-C.