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No benefit to reducing LDL levels below 70 mg/dL with statin therapy

Recent findings published in JAMA Internal Medicine showed that reducing LDL cholesterol levels below 70 mg/dL did not result in any added benefit for patients undergoing statin therapy.

“Results from recent clinical trials of statins in combination with adjunctive medications for secondary prevention have led to renewed emphasis on the concept that ‘lower is better’ for target LDL [cholestrol] levels,” Morton Leibowitz, MD, at Clalit Research Institute in Israel, and colleagues wrote. “The present population-based observational study examines whether the principle of lower is better is applicable to long-term treatment of patients with [ischemic heart disease] in the community setting, by assessing the relationship between observed LDL [cholesterol] levels and cardiovascular outcomes in the largest health care organization in Israel.”

The American Heart Association’s guidelines do not establish target LDL levels, but the European Society of Cardiology recommends an LDL level below 70 mg/dL, the researchers wrote.

To assess whether this recommendation reduced the incidence of cardiac events, the researchers performed an observational study of patients on statin therapy for ischemic heart disease between 2009 and 2013 in Israel. Patients were aged between 30 and 84 years and were excluded if they had active cancer or any metabolic abnormalities, and were at least 80% adherent to treatment. Patients who were at least 50% adherent were also included in a sensitivity analysis. Adverse cardiac events included stroke, angioplasty, bypass surgery, unstable angina, all-cause mortality and myocardial infarction.

The cohort with at least 80% adherence included 31,619 patients, with a mean age of 67.3 years. In this group, the researchers found that the adjusted incidence for adverse outcomes was no different for patients with an LDL level lower than 70 mg/dL compared with those who had an LDL level between 70 and 100 mg/dL (HR = 1.02; 95% CI, 0.97-1.07). However, there was a lower incidence for patients with an LDL level between 70 and 100 mg/dL compared with those who had an LDL level between 100 and 130 mg/dL (HR = 0.89; 95% CI, 0.84-0.94; P < .001).

The sensitivity analysis included 54,884 patients. The adjusted HR was 1.06 in the low vs. moderate LDL level group (95% CI, 1.02-1.1). and 0.87 in the moderate vs. high LDL level group.

In a related commentary, Simon B. Ascher, MD, MPH, resident physician at the University of California, San Francisco School of Medicine, and colleagues wrote that this study helps clarify the goals of long-term statin therapy.

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

Disclosures: The researchers report no relevant financial disclosures.