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Niacin lowered PCSK9 levels
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Niacin is associated with a reduction in PCSK9 levels, according to new findings.
This association could help explain how niacin reduces LDL, and could offset increases in PCSK9 levels associated with other lipid-lowering therapies, researchers wrote.
PCSK9 is a secreted protease that binds to the LDL receptor in the liver, contributing to degradation of the receptor and increasing LDL levels, according to the study background. Results from previous research indicated that statin therapy can increase circulating PCSK9 levels — potentially limiting additional reduction of LDL at higher doses — and that fibrates may also increase PCSK9 levels, the researchers wrote.
Amit V. Khera, MD, MSc, FACC, and colleagues conducted three studies to determine the dose-dependence effects of statins on PCSK9 levels, to assess the effect of a fibrate on PCSK9 levels when added to a statin, and to investigate the impact of niacin on PCSK9 levels on the background of statin and/or fibrate therapy.
In the first study, 74 people with hyperlipidemia were randomly assigned atorvastatin 10 mg/day, atorvastatin 80 mg/day or placebo for 16 weeks.
Khera, from the cardiology division of the department of medicine at Massachusetts General Hospital, and colleagues found that PCSK9 levels were increased in a dose-dependent fashion with statin therapy compared with placebo (placebo, mean increase 7%; 95% CI, –7 to 21; atorvastatin 10 mg/day, mean increase 19%; 95% CI, –5 to 42; atorvastatin 80 mg/day, mean increase 27%; 95% CI, 12-42; P=.02 vs. placebo).
In the second study, 70 patients with carotid atherosclerosis were randomly assigned simvastatin 20 mg/day, simvastatin 80 mg/day or simvastatin 20 mg/day plus extended-release niacin 2 g/day for 12 months.
The researchers found that PCSK9 levels increased with statin therapy (simvastatin 20 mg/day, mean change 13%; 95% CI, –14 to 40; simvastatin 80 mg/day, mean change 41%; 95% CI, 27-76; P<.0001), but that PCSK9 decreased with combination simvastatin/niacin therapy (mean change –13%; 95% CI, –3 to –23).
In a third, open-label lipid kinetics study, 19 people with dyslipidemia were treated with atorvastatin 10 mg/day for 4 weeks, followed by the addition of fenofibric acid 135 mg/day for 8 weeks, and then the further addition of extended-release niacin 2 g/day for 10 weeks.
Adding fenofibric acid led to a 23% (95% CI, 10-36) increase in PCSK9 (P=.001), but the addition of niacin resulted in a subsequent 17% (95% CI, –19 to –5) decrease in PCSK9 (P=.004), according to the researchers. They also found a positive association between changes in PCSK9 levels and changes in LDL levels (P=.006) induced by the addition of niacin.
“Niacin therapy offsets the increase in PCSK9 levels noted with statin and fibrate therapy,” Khera and colleagues wrote. “A portion of the [LDL] cholesterol reduction seen with niacin therapy may be due to reduction in PCSK9.”
Editor's Note: On Sept. 10, 2015, this article was updated to correct the affiliation of Amit V. Khera, MD. The Editors regret this error.
Disclosure: One researcher was supported by an NIH grant.
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