CHICAGO—A post hoc analysis suggests that achieving both a low-density lipoprotein cholesterol (LDL-C) level <70 mg/dL and a triglyceride level <150 mg/dL can reduce the risk of coronary heart disease (CHD) following an acute coronary syndrome (ACS).

This finding, from the PROVE IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy) study, which was designed to compare the clinical efficacy of intensive (<70 mg/dL) and less-intensive (<100 mg/dL) LDL-C lowering in ACS patients, was reported by Michael Miller, MD, at the American Heart Association annual meeting.

PROVE IT demonstrated that intensive LDL-C lowering using atorvastatin (Lipitor), 80 mg/day, was associated with a greater reduction in CHD event rates compared with standard lipid lowering with pravastatin (Pravachol), 40 mg/day, after an ACS. Although lowering LDL-C is a primary goal for patients with CHD, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III also cites triglyceride reduction as a secondary target.

The extent to which “desirable” triglyceride levels (ie, <150 mg/dL) may improve CHD risk beyond LDL-C reduction had not been explored, providing the rationale for this analysis, said Dr Miller, director of the Center for Preventive Cardiology, University of Maryland Medical Center, Baltimore.

On-treatment levels of triglycerides and LDL-C in the 4162 patients (average age, 58 years) in PROVE IT were assessed at 30 days, 4 months, and 8 months; the composite end point of death, myocardial infarction, recurrent ischemia, or unstable angina was assessed according to LDL-C and triglyceride levels.

An LDL-C level of >70 mg/dL was associated with a 32% increased CHD event risk compared with an LDL-C ≤70 mg/dL. An isolated triglyceride level of >150 mg/dL was associated with a 34% increased risk of an event compared with a triglyceride level ≤150 mg/dL.

“The lowest risk of an event occurred with an LDL <70 and a triglyceride level <150,” said Dr Miller. Designating patients who achieved both targets as the reference group, the risk of the primary end point increased by 66% in patients who did not achieve either target (P <.05) and increased by lesser amounts in patients achieving just one.

When C-reactive protein (CRP) was added to the analysis, achieving an LDL-C <70 mg/dL, a triglyceride level <150 mg/dL, and a CRP <2 mg/L was associated with a 53% to 61% risk reduction, depending on the time interval studied, compared with reaching none of the 3 targets.

“Achieving low triglycerides beyond LDL and CRP may be an important therapeutic goal in patients following ACS,” said Dr Miller. He postulated that large reductions in all 3 may combine to reduce the risk via plaque stabilization (LDL-C), less atherothrombosis (triglycerides), and decreased inflammation (CRP).

Peter Jones, MD, noted that triglyceride levels >150 mg/dL but <500 mg/dL may be the result of insulin resistance, which occurs in patients with diabetes and/or the metabolic syndrome. Nevertheless, he said, “we’re not giving our patients the best opportunity to reduce the risk of events if we only lower LDL.” He considers adding niacin or fenofibrate (Tricor) to a statin in patients whose triglycerides remain high despite statin therapy, noting that less-than-optimal compliance with niacin may be a limiting factor to its use.

Ongoing trials are specifically addressing intensive lowering of both LDL-C and triglycerides as primary goals to further reduce CHD risk.