By David Ramsey, EPA 2015

Background statin therapy, even the use of high-dose statin therapy, did not affect the ability of alirocumab (Sanofi/Regeneron) to reduce LDL-cholesterol levels in patients at high cardiovascular risk, delegates heard at the European Atherosclerosis Society 2015 Congress, Glasgow.

According to a new analysis of 4000 patients, investigational inhibitor of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, alirocumab reduced LDL-cholesterol levels by 47% to 62% among patients also treated with a high-dose statin.

"Alirocumab is a monoclonal antibody for PCSK9 that has been shown to provide an additional LDL reduction, roughly a 50% decrease," said Krempf, lead researching of the trial during his EAS presentation. "We also know that statins are known to increase the concentration of PCSK9, which is one of the paradoxes of statin therapy."

“In patients treated with high-intensity statins compared with non–high-intensity statins, higher plasma PCSK9 levels could be expected, and this could potentially reduce the efficacy of the same dose of PCSK9 inhibitor,” said Krempf.

The LDL-lowering response to alirocumab was not affected by high-intensity statin treatment, according to the results. The least square mean reduction in LDL ranged from 47% to 62% on high-intensity statin treatment vs. 35% to 61% reduction on non–high-intensity statin treatment.

In the largest trial analyzed, ODYSSEY LONG TERM (n = 2,310), treatment with alirocumab was associated with a 62% reduction in LDL for patients on high-intensity statin therapy and a 61% reduction in LDL for those on non–high-intensity statin therapy.

A separate analysis evaluated LDL cholesterol goal attainment in eight Phase 3 trials in patients at high cardiovascular risk on statin treatment with or without other lipid-lowering therapy.2 Patients in these trials were allocated to treatment with alirocumab (75 mg every 2 weeks increasing to 150 mg every 2 weeks at week 12 if LDL cholesterol levels were above guideline-recommended LDL cholesterol goal at week 8, or 150 mg every 2 weeks), placebo or ezetimibe. 

At week 24, alirocumab reduced LDL cholesterol from baseline by 49 percent (75/150 mg every 2 weeks) and by 60 percent with 150 mg every 2 weeks (p<0.0001). Across the trials, 75-79 percent of patients achieved LDL cholesterol goal (<1.8 or <2.6 mmol/L). 

In both analyses, alirocumab was generally well tolerated. Local injection site reactions, influenza and pruritus were the most common adverse events among alirocumab-treated patients. Commenting on both trials, Professor Anthony Wierzbicki, Consultant in Metabolic Medicine/Chemical Pathology, Guy’s and St Thomas' Hospital NHS Trust, London, UK said: ‘These data provide further support for the efficacy of PCSK9 inhibitors in significantly lowering LDL cholesterol consistently across all categories of patients and previous therapeutic regimens without any evidence of increased treatment-emergent adverse events.’

These data add to growing evidence suggesting a future role for these novel treatments to improve the management of patients at high risk of heart attack or stroke who commonly do not achieve LDL cholesterol targets despite best treatment including high intensity statins.