Statin-Taking Patients With LDL-C of 70–100 mg/dL at Decreased Risk of MACE

Deborah Brauser

July 06, 2016

TEL AVIV, ISRAEL — Although the European Society of Cardiology (ESC) currently recommends that long-term statin treatment for patients with CAD should target LDL-C levels less than 70 mg/dL, new research suggests that the optimal level is actually a bit higher[1].

A population-based study of more than 31,000 statin-taking adults in Israel who had stable ischemic heart disease showed no significant differences in major adverse cardiac events (MACE) between those with LDL-C levels that were between 70 and 100 mg/dL after 1 year of treatment and those with LDL-C <70 mg/dL.

However, there was a significantly lower risk for MACE in those with LDL-C of 70 to 100 mg/dL vs those with LDL-C levels of 100 to 130 mg/dL (P<0.001).

The investigators, led by Dr Morton Leibowitz (Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel), note that these results "do not provide support for a blanket principle that lower LDL-C is better for all patients in secondary prevention."

When asked whether any of the findings surprised him, Leibowitz told heartwire from Medscape via email that "we were very pleased with the robustness of the findings. Below 100 mg/dL made a difference; below 70 mg/dL did not." And the number-one takeaway message? "Don't accept 'lower is better' for all patients."

The results were published online June 20, 2016 in JAMA Internal Medicine.

An accompanying editor's note[2], led by Dr Simon B Ascher, states that although "statins are a staple of secondary prevention" in CVD, there has been controversy over how best to determine treatment dose and whether that should be based on LDL-C levels or not.

"This retrospective study represents an important effort in clarifying goals for long-term statin therapy," they write, agreeing with Leibowitz that the findings suggest that targeting <100 mg/dL levels results in the same reduced CV risk "as more aggressive LDL-C targets."

Debate Continues

As reported by heartwire ,American College of Cardiology/American Heart Association guidelines released in 2013 moved away from targeting specific LDL levels because of a lack of scientific evidence. But this action continues to be debated.

On the other hand, the ESC 2012 guidelines recommend targeting to an LDL-C level of <70 mg/DL.

For the current study, the researchers sought to examine whether this "lower-is-better" strategy really is advantageous in a real-world, community setting. They assessed records from 2009 through 2013 for 31,619 patients enrolled in Israel's Clalit Health Services who were between the ages of 30 and 84 years (mean age 67.3 years; 73% men) and who were at least 80% adherent to their treatment with statins, based on prescription fulfillment.

"Index LDL-C was defined as the first achieved serum LDL-C measure after at least 1 year of statin treatment, grouped as low (<70.0 mg/dL), moderate (70.01–100.0 mg/dL), or high (100.1–130.0 mg/dL)," explain the investigators. There were 9086, 16,782, and 5751 patients in each of the groups, respectively.

The primary outcome was MACE, which included a composite of acute MI, unstable angina, angioplasty or bypass surgery, stroke, or all-cause mortality.

At a mean of 1.6 years of follow-up, 9035 of the patients had a MACE (6.7 per 1000 persons per year). The moderate LDL-C group had significantly fewer MACE (27.4%) vs both the low LDL-C group (29.5%) and the high LDL-C group (30.6%; both comparisons P<0.001).

The adjusted hazard ratio (HR) for MACE was a nonsignificant 1.02 for the low vs moderate LDL-C groups (95% CI 0.97–1.07, P=0.54). However, the adjusted HR was significantly lower in the moderate vs high LDL-C groups, at 0.89 (95% CI 0.84–0.94).

In further analyses, the investigators expanded their examination to 54,884 patients—all of whom had >50% treatment adherence. In this cohort, the low LDL-C group had a higher risk of MACE vs the moderate group (HR 1.06, 95% CI 1.02–1.10), whereas the moderate group had a lower risk vs the high LDL-C group (HR 0.87, 95% CI 0.84–0.91, both comparisons P=0.001).

Absolute Instead of Relative LDL-C?

Leibowitz added that the key clinical question when the investigators undertook this study was: if a patient has stable CAD, is taking statins, and has achieved a reasonable reduction in LDL-C, "how compelling is it to push below 70 mg/dL? Given the advent of new expensive medications that lower LDL cholesterol but have not yet demonstrated impact on events, how critical is the achieved LDL level?"

After seeing the results, he noted that the take-home message for clinicians is to "look at each patient critically when deciding to add secondary lipid-lowering medications."

Expounding on this, Ascher et al write in their editor's note that targeting an LDL-C level of less than 100 mg/dL instead of a level of less than 70 mg/dL may "help to minimize adverse effects that are more common with higher statin doses needed for lower LDL targets while maximizing benefits."

"The findings . . . also support consideration of absolute LDL-C levels instead of relative LDL-C percentage reductions in gauging an adequate response to statin therapy and raise questions about the practice of statin dosing by intensity."

They conclude by noting that, overall, the study "adds important information" to continued discussions about these topics.

The study was funded by the Clalit Research Institute. The study authors and editorialists report no relevant financial relationships.

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