Tel Aviv, Israel—Treatment guidelines recommending very low target low-density lipoprotein cholesterol (LDL-C) levels for all patients with pre-existing heart disease are not supported by population-based data, according to a large new international study.

The study, published recently in JAMA Internal Medicine, points out that while guidelines urging treatment with statins for patients with pre-existing ischemic heart disease to prevent additional cardiovascular events are fairly universal, they differ regarding recommended target levels of LDL-C.

The Clalit Research Institute–led study team, which also included participation from U.S. and Canadian researchers, notes that data has been inconclusive and observational information is lacking on what those levels should be. To remedy that, the researchers sought to assess the relationship between levels of LDL-C achieved with statin treatment and cardiovascular events in adherent patients with pre-existing ischemic heart disease.

Their population-based observational cohort study from 2009 to 2013 used data from a healthcare organization in Israel covering more than 4.3 million members. The cohort of 31,619 included patients with a median age of 67.3, tended to be male (more than 70%), had ischemic heart disease, were treated with statins, and were at least 80% adherent to treatment or, in a sensitivity analysis, at least 50% adherent. Excluded were patients with active cancer or metabolic abnormalities.

The study defined index LDL-C as the first achieved serum LDL-C measure after at least 1 year of statin treatment and grouped it as low, 70.0 mg/dL or below; moderate, 70.1-100.0 mg/dL, or high, 100.1-130.0 mg/dL. Of the participants, 29% had low, 53% moderate, and 18% high LDL-C when on statin therapy.

Major adverse cardiac events were considered to be acute myocardial infarction, unstable angina, stroke, angioplasty, bypass surgery, or all-cause mortality.

Results indicate that, for the 9,035 patients who had an adverse outcome during a mean 1.6 years of follow-up, the adjusted incidence of adverse outcomes was not different between low and moderate LDL-C with a hazard ratio (HR) of 1.02. It was lower, however, with moderate versus high LDL-C, with an HR of 0.89.

Among 54,884 patients with at least 50% statin adherence, the adjusted HR was 1.06 in the low-versus-moderate groups and 0.87 in the moderate-versus-high groups, according to the study.

“Patients with LDL-C levels of 70 to 100 mg/dL taking statins had lower risk of adverse cardiac outcomes compared with those with LDL-C levels between 100 and 130 mg/dL, but no additional benefit was gained by achieving LDL-C of 70 mg/dL or less,” study authors conclude.

An editor’s note called the study “an important effort in clarifying goals for long-term statin therapy.”

“The findings suggest that targeting an LDL-C level of less than 100 mg/dL achieves the same cardiovascular risk reduction as more aggressive LDL-C targets, which could help to minimize adverse effects that are more common with higher statin doses needed for lower LDL targets while maximizing benefits,” according to the commentary. “The finding of improved outcomes below a threshold LDL-C level also supports consideration of absolute LDL-C levels instead of relative LDL-C percentage reductions for gauging an adequate response to statin therapy and raises questions about the practice of statin dosing by intensity.”

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