News & Trial Summaries

CANTOS evaluated canakinumab, an interleukin-1β inhibitor, versus placebo in patients with prior myocardial infarction and elevated high-sensitivity CRP (≥2 mg/L) despite standard therapy, testing the inflammatory hypothesis of atherosclerosis independent of lipid lowering.

Key takeaways: Canakinumab significantly reduced recurrent cardiovascular events without altering LDL cholesterol, providing landmark proof-of-concept that targeting inflammation directly can lower cardiovascular risk; it also reduced lung cancer incidence/mortality in exploratory analyses.

VESALIUS-CV tested evolocumab, a PCSK9 inhibitor, versus placebo added to optimized statin therapy in over 12,000 adults with atherosclerosis or high-risk diabetes but without a prior MI or stroke — extending PCSK9 inhibition into a broader primary-prevention-leaning population than earlier trials like FOURIER.

Key takeaways: Evolocumab lowered LDL-C to a median in the 30–45 mg/dL range and reduced the primary composite endpoint (CHD death, MI, or ischemic stroke) by 25%, with consistent benefit including in the large diabetic subgroup and in patients without known significant atherosclerosis, supporting earlier and more aggressive LDL-lowering before a first major event.

Ez-PAVE was the first head-to-head randomized trial directly comparing two LDL-C targets (rather than two drugs) — intensive (<55 mg/dL) versus conventional (<70 mg/dL) — in about 3,000 South Korean patients with established atherosclerotic cardiovascular disease, using a pragmatic, open-label, treat-to-target design with statins, ezetimibe, and PCSK9 inhibitors as needed.

Key takeaways: The intensive LDL-C target reduced the composite cardiovascular endpoint by roughly one-third (33% relative risk reduction) over three years compared with the conventional target, providing direct randomized support for guideline-recommended lower LDL-C goals in secondary prevention.

CATALYST (Part 1, the prevalence phase) was a prospective, two-part, multicenter study at 36 U.S. specialized diabetes centers designed to determine how common unrecognized hypercortisolism (Cushing's syndrome) is among people with "difficult-to-control" type 2 diabetes. 1,057 adults aged 18–80 with HbA1c 7.5–11.5% despite multiple standard-of-care therapies (≥3 glucose-lowering medications or insulin plus other agents) were screened with an overnight 1 mg dexamethasone suppression test (DST), with hypercortisolism defined as failure to suppress post-DST cortisol to ≤1.8 µg/dL.

Key takeaways: Hypercortisolism was identified in 23.8% (about one in four) of participants — substantially higher than prior estimates. Prevalence rose to roughly one in three among patients on three or more antihypertensive medications, and about one-third of those with hypercortisolism had an adrenal abnormality on CT imaging. The findings suggest hypercortisolism is a meaningfully common, underrecognized contributor to poor glycemic control and may represent a treatable driver of "difficult-to-control" diabetes rather than just refractory disease itself.

REDUCE-IT tested high-dose icosapent ethyl (a purified EPA omega-3 fatty acid) versus mineral oil placebo in statin-treated patients with elevated triglycerides who had established cardiovascular disease or diabetes plus risk factors.

Key takeaways: Icosapent ethyl reduced the primary composite cardiovascular endpoint (CV death, MI, stroke, revascularization, unstable angina) by about 25% relative risk reduction, one of the largest benefits seen with an add-on lipid therapy in the statin era, with benefit appearing to exceed what triglyceride lowering alone would predict.