Lipid management guidelines should be revised to reflect evidence of clinical benefits of lowering LDL-cholesterol levels below the current target of 1.8mmol/l, lipid researchers say.
A meta-analysis of trials of statin and non-statin therapies has shown that reductions in major vascular events are apparent when LDL-C levels are lowered to 1.6 mmol/L and the benefits are consistent for reductions as low as 0.5 mmol/L.
Overall there was a 21% relative risk reduction per 1 mmol/L reduction in LDL-C, according to the meta-analysis that covered 26 statin trials and three trials of non-statin therapies in secondary prevention of cardiovascular disease.
The clinical benefits seen with additional LDL-C lowering are seen across all agents and can be achieved with “no offsetting safety concerns” the study authors say.
Published in JAMA Cardiology, the review notes that current guidelines recommend a target LDL-C level of less than 2 mmol/L in an era when lower levels are achievable with intensive statin therapy in combination with ezetimibe and new agents such as CETP inhibitors and PCSK9 inhibitors.
“These data suggest further lowering of LDL-C thresholds for initiating more intensive therapy, or simply targeting LDL-C at least as low as approximately 0.5 mmol/L … would further reduce cardiovascular risk,” the authors conclude.
However an editorial commentary cautions that the non-statin trials were of relatively short duration, and uncommon adverse effects may take a long time to be detected, as seen with the metabolic effects of statins.
“While it is possible to calculate how low LDL-C levels can be reduced while still detecting a cardiovascular benefit, one reaches a point of diminishing returns, and it is not clear how low it is safe to go,” it states.
Nevertheless, the commentary by Professor Antonio Gotto of Cornell University says the data provide a strong case for updating the current lipid guidelines to reflect lower LDL-C levels.
Whether one calls it a target or a threshold, practicing physicians need some guidance as they venture into achieved levels of LDL-C levels that are as foreign as travel to outer space.
Professor David Sullivan, Head of Chemical Pathology at the Royal Prince Alfred Hospital, Sydney, said that unlike other risk factors such as blood pressure it was possible to go lower than current targets with LDL-cholesterol levels without causing harm.
“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.
“The accompanying editorial points out that the new information that has been included in the study warrants revision of the 2013 American guidelines on lipid management. This need is even more pressing in Australia where the guidelines are considerably older.”
Australian lipid management guidelines were last updated in 2012, at which time they recommended a target LDL-C level of below 1.8 mmol/L. RACGP guidelines recommend a target of below 2 mmol/L.