Study Questions ‘Lower Is Better’ For Cholesterol

–No added benefit for statin patients who reached very low LDL levels

A large observational study suggests that moderate lowering of LDL may be just as effective as intensive lowering. “Our results do not provide support for a blanket principle that lower LDL cholesterol is better for all patients in secondary prevention,” the authors conclude.

In a paper published in JAMA Internal Medicine, Israeli researchers analyzed data from 31,000 patients with ischemic heart disease who received statins and remained adherent to treatment. They compared the rate of major adverse cardiac events (MACE) in three groups of patients based on their LDL levels after at least 1 year of treatment: 9,086 had low LDL levels (below 70 mg/dL), 16,782 had moderate LDL levels (70 to 100 mg/dL), and 5,751 had high LDL levels (over 100 mg/dL).

There was no significant difference in MACE between the low group and the moderate group but there was a significant reduction in events in the moderate group when compared to the high group. The adjusted rate of events per 1,000 person-years was 78.1 in the low group, 71 in the moderate group, and 81.3 in the high group. The same pattern emerged in a propensity-matched population.

Current European guidelines recommend that patients with ischemic heart disease receive treatment with a target of 70 mg/dL or below. U.S. guidelines no longer recommend targets, but a substantial proportion of lipid experts still believe in aggressive treatment targets. The results of the new study suggest that an aggressive target may not offer any additional advantage over a moderate target.

The study “represents an important effort in clarifying goals for long-term statin therapy,” write the journal’s editors in an Editor’s Note. “The findings suggest that targeting an 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.”

But outside experts questioned the use an observational study like this to inform the cholesterol debate. “It is very, very hard to make conclusions from non-randomized retrospective studies like this,” said Michael Blaha, MD, MPH, of Johns Hopkins.


  1. I’m confused, Larry. As you correctly point out, “U.S. guidelines no longer recommend targets, but a substantial proportion of lipid experts still believe in aggressive treatment targets.”

    Didn’t the 2013 guidelines specifically warn docs that those arbitrary targets for lowering LDL numbers we’d been believing all those years are in fact “unsupported by scientific evidence”? And how many more new studies – observational or otherwise – do we really need to keep on confirming the already-confirmed?

    • Larry Husten says

      You are right, but it’s also clear that there is no really firm, evidence base for any particular approach. Many lipid experts still believe in specific targets.

      • I know…. which merely confirms my theory: if low-risk healthy individuals want to know if they should be taking statins, this qualifying question should be posed:

        “Do I have a detectable pulse?”

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