Should ‘bad’ cholesterol be lowered further?

cholesterol in an artery

People with already low levels of LDL-cholesterol may benefit from drug therapy to lower it even further, new research suggests

The US research, published in JAMA, pooled the results of previous studies in order to look specifically at people with levels of “bad cholesterol” that were already below the current guidelines.

When these people were given medicines to lower their cholesterol further, there was a reduction in major vascular events, without an increased risk of serious adverse events.

The Cholesterol Treatment Trialists Collaboration (CTTC) was used for statin data, while for non-statin therapy the Medline database was searched (2015 – April 2018).

Key inclusion criteria were a randomised, double-blind, controlled cardiovascular outcome trial of LDL-C lowering with data in populations starting with LDL-C levels averaging 1.8 mmol/L (70 mg/dL) or less.

“In the subgroup of patients from the CTTC meta-analysis of statins with a mean LDL-C in the control arm of 1.7 mmol/L (65.7 mg/dL), 1922 major vascular events occurred and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.78 (95% CI, 0.65-0.94),” the authors write.

“For three trials of nonstatin LDL-C–lowering therapies added to statins, there were 50,627 patients, the median LDL-C in the control arms ranged from 1.6 mmol/L to 1.8 mmol/L (63 mg/dL to 70 mg/dL), and 9570 major vascular events occurred.

“Nonstatin therapy lowered LDL-C by 0.3 to 1.2 mmol/L (11 mg/dL to 45 mg/dL), and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.79 (95% CI, 0.70-0.88).

“For statins and nonstatins combined, the RR was 0.79 (95% CI, 0.71-0.87; P < .001). Low-density lipoprotein cholesterol lowering was not associated with an increased risk of serious adverse events, myalgias and/or myositis, elevation in the level of aminotransferases, new-onset diabetes, hemorrhagic stroke, or cancer.

“There is a consistent relative risk reduction in major vascular events per change in LDL-C in patient populations starting as low as a median of 1.6 mmol/L (63 mg/dL) and achieving levels as low as a median of 0.5 mmol/L (21 mg/dL), with no observed offsetting adverse effects,” the authors write.

“These data suggest further lowering of LDL-C beyond the lowest current targets would further reduce cardiovascular risk.”

Dr David Sullivan, Head of Chemical Pathology at the Royal Prince Alfred Hospital in NSW, says that the analysis is an important one.

“Blood pressure and blood glucose lowering treatments have limitations because overly aggressive therapy will cause symptoms such as fainting or loss of consciousness,” Dr Sullivan says.

“This analysis is very important because it suggests that there is no such threshold for LDL cholesterol-lowering treatment.

“The greatest benefit from further reducing already low LDL cholesterol levels will be seen in patients with the highest risk of cardiovascular disease, including those with peripheral vascular disease and those in whom arteries continue to narrow despite usual therapy.”

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  1. Daniel Hackett

    An industry sponsored study found a higher incidence of cataracts (the lens of the eye synthesizes cholesterol for structure and clarity), and excess neurocognitive adverse events associated with low LDL cholesterol. One can only imagine what a proper study would find.

  2. Melanie Makris

    I have been reading lately, about the 7 subtypes of LDL cholesterol. Subtypes LDL-1 and LDL-2 are GOOD for us because they deliver the cholesterol to where it is required in the body for repair and hormone synthesis, while subtypes 3 to 7 are smaller and denser and more prone to oxidative stress. Add to this the story of ApoB and ApoA1, where ApoB wraps around LDL and is more prone to damage via oxidative stress versus ApoA1 which transports HDL particles and is less susceptible to damage. I would be keen to learn if population variations in the subtypes of LDL and the ratio of apoB:apoA1 have ever been taken into consideration. If NOT, then how can these studies be called RCT??

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