Lower LDL-C Levels Don't Attenuate Cholesterol-Lowering Drug Effects

Patients with lower baseline levels of low-density lipoprotein cholesterol (LDL-C) have a greater percentage reduction of LDL-C with statins, ezetimibe and PCSK9 inhibition than do those with higher LDL-C, new findings show.

The difference was largest for PCSK9 inhibition, Dr. Marc S. Sabatine of Brigham and Women's Hospital in Boston and colleagues report in JAMA Cardiology. Their findings were also presented November 13 at the American Heart Association Scientific Sessions 2020 virtual conference.

"We have traditionally thought that the percentage LDL cholesterol lowering with the various drugs we use is constant across a range of baseline LDL cholesterol levels, but it turns out that the percentage LDL lowering is actually greater in patients who are starting with lower levels of LDL cholesterol, and that effect is most pronounced with evolocumab, a PCSK9 inhibitor," Dr. Sabatine told Reuters Health by phone. "That's good news, because we know that the clinical benefit from LDL cholesterol reduction is going to be a function of the absolute reduction in LDL cholesterol."

​

As the benefits of LDL-C reduction for reducing cardiovascular risk have been shown to persist even at levels below 38.61 mg/dL, guidelines are recommending lower LDL-C targets, Dr. Sabatine and his team note.

To investigate whether patients with lower LDL-C levels would see the same benefit from cholesterol-lowering therapy as those with higher LDL-C, Dr. Sabatine and his team looked at the A to Z-TIMI 21, IMPROVE-IT and FOURIER trials, all in patients with existing cardiovascular disease.

Their analysis included more than 2,000 patients from A to Z-TIMI 21, 10,000 from IMPROVE-IT and 25,000 from FOURIER.

For patients on evolocumab, baseline LDL-C was reduced by 59.4% in patients with an LDL-C level of 130 mg/dL and by 66.1% in those with LDL-C of 70 mg/dL (P<0.001).

Patients on simvastatin had 44.6% and 47.8% reductions in LDL-C (P<0.001), respectively. For ezetimibe, the reductions were 25.0% and 26.2% (P=0.007).

"To put the data in perspective, the additional 6.6% greater LDL-C lowering with evolocumab is what one expects for doubling a statin dose," the authors write. "Such data are encouraging for reaching the progressively lower LDL-C targets that are being set, particularly for those defined in the guidelines as being at very high risk."

Dr. Sabatine and other study authors report financial relationships with makers of cholesterol-lowering medications.

—Anne Harding

Source