Statin, some nonstatin lipid-lowering therapies broadly equivalent
medwireNews: Nonstatin therapies that act via upregulation of the low-density lipoprotein (LDL) receptor prevent major vascular events as effectively as statins do, shows an analysis in JAMA.
But for other medications, the efficacy depended on the means by which cholesterol levels are lowered, report Marc Sabatine (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and study co-authors.
They found that therapies that predominantly lowered cholesterol via LDL receptor upregulation – diet, bile acid sequestrants, ileal bypass and ezetimibe – reduced the risk of major vascular events by 25% per 1 mmol/L reduction in LDL cholesterol.
Statins had a similar effect, reducing the risk by 23% per 1 mmol/L reduction in LDL cholesterol. And for both categories of treatment there was a significant association between absolute achieved LDL cholesterol and vascular event rates.
The researchers stress the guideline recommendations that statins should be the first-line treatment, given their proven effectiveness and tolerability, in addition to their affordability, with most now being generic.
“However, the data in the present meta-regression analysis raise the possibility that other interventions, especially those that ultimately act predominantly through upregulation of LDL receptor expression, may provide additional options and may potentially be associated with the same relative clinical benefit per each 1-mmol/L reduction in LDL-[cholesterol]”, they say.
The analysis included 49 trials, including 25 statin trials and eight trials of therapies that act predominantly via LDL receptor upregulation. There were also 17 trials involving therapies that lower cholesterol through other means, namely, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
The degree to which these other drugs were cardioprotective varied according to the underlying mechanism of action. For niacin, the meta-regression predicted a significant 9% reduction in vascular events per 1 mmol/L reduction in LDL cholesterol, but the observed reduction was 6%. Fibrates, on the other hand, produced a 12% reduction when only 6% was predicted, with the increased efficacy due to their ability to reduce levels of the smallest, most atherogenic lipoprotein particles.
The researchers note that recent trials failed to demonstrate the efficacy of niacin and fibrates for vascular outcomes, “calling into question the clinical utility of these drugs.” But, based on their meta-regression findings, they believe that the HPS2-Thrive, FIELD and ACCORD trials were statistically underpowered to detect an effect on the primary outcome, with ACCORD notably having just 3% statistical power.
CETP inhibitors were expected to produce a 10% vascular risk reduction per 1 mmol/L reduction in LDL cholesterol, but had no observable effect. PCSK9 inhibitors had an observed 51% risk reduction, which was greater than the expected 39% reduction, but not significantly so.
Statins and interventions that predominantly lowered cholesterol via LDL receptor upregulation had cardioprotective effects that were in line with their expected effects.
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