HDL-C Not Determinant in Improved CAD Treatment

Toshiyuki Nagai, MD, PhD

High-density lipoprotein cholesterol (HDL-C) do not serve great prognostic value in patients with stable coronary artery disease (CAD) treated with statins, according to new data.

In findings from the REAL-CAD study presented virtually during the European Society of Cardiology (ESC) 2020 Congress this week, a team of Japan-based investigators reported the association between HDL-C and cardiovascular events among statin-treated patients with CAD who have controlled low-density lipoprotein cholesterol (LDL-C) is not significant.

Led by Toshiyuki Nagai, MD, PhD, of Hokkaido University in Sapporo, investigators conducted the post-hoc analysis of the randomized, open-label Randomized Evaluation of Aggressive or Moderal Lipid Lowering Therapy with Pitavastatin in CAD (REAL-CAD) trial, which initially enrolled patients from January 2010 to March 2013, and conducted follow-up through January 2016.

Patients were originally assessed for a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission post-six months randomization.

Nagai and colleagues created landmark Cox proportional hazards regression models with 18 selected, clinically relevant risk-adjusting variables during the entire follow-up period of REAL-CAD starting at 6 months post-randomization.

The team excluded original trial patients without either baseline or six-month HDL-C data, as well as those to have a primary outcome occur at 6 months and those with reported poor adherence to the statin therapy. This reduced the observed population from 14,774 REAL-CAD participants to 9221 analysis-eligible patients.

Median patient age was 70 years old, with 83% being male. Median HDL-C levels were 49 mg/dL, as well as a median LDL-C level of 88 mg/dL.

Over a median follow-up period of 4 years, investigators observed a primary outcome in 417 (4.5%) patients. They found no significant difference in crude and adjusted cumulative primary outcome events among the quartiles of six-month HDL-C levels.

They also found no significance in the adjusted risks of all HDL-C related variables for the primary outcome in their ad hoc.

Additionally, the adjusted hazard ratio (HR) was non-significant as HDL-C increased by 10 mg/dL at 6 months, for on-treatment LDL-C levels of <70 mg/dL (HR, 0.97; 95% CI, 0.82 – 1.15), 70-100 mg/dL (HR, 1.10; 95% CI, 0.98 – 1.24), and ≥100 mg/dL (HR, 0.94; 95% CI, 0.78 – 1.13) at 6 months.

Lastly, investigators observed no significant link between HDL-C level at 6 months and primary outcome in low (1 mg daily) and high (4 mg daily) dose pitavastatin groups. HRs were 1.02 and 1.04, respectively.

“After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable coronary artery disease,” investigators wrote.

The study, “High-density lipoprotein cholesterol does not predict future cardiovascular events in patients treated with statins for secondary prevention: an observation from the REAL-CAD study,” was presented at ESC 2020.