High intensity statin therapy does not affect LDL-c lowering with a PCSK9 inhibitor
24/03/2015
Although statins increase plasma PCSK9 concentrations, high intensity statin therapy did not reduce the efficacy of PCSK9 inhibitor alirocumab, shows an analysis involving over 4000 patients.
High intensity statin therapy does not affect LDL cholesterol lowering with the PCSK9 inhibitor alirocumabNews - Mar. 25, 2015
Presented as a Clinical Latebreaker at the EAS 83rd Annual Congress, Glasgow, Scotland, UK (March 21-25, 2015)
In an analysis of six alirocumab trials involving more than 4000 patients, lowering of LDL-c with this PCSK9 antibody was not influenced by background high intensity statin therapy.
It is well known that statins increase plasma PCSK9 concentration, which could potentially reduce the efficacy of PCSK9 inhibitors. This hypothesis was tested in an analysis of 4166 patients receiving background treatment with a maximally tolerated dose of high intensity statin or non-high intensity statin. Five trials also allowed for non-statin lipid-lowering treatment. All patients were at high cardiovascular risk (18% with heterozygous familial hypercholesterolaemia). Patients received alirocumab injection (75 mg increasing to 150 mg every 2 weeks if the LDL-c goal was not achieved, or 150 mg every-2 weeks), placebo or the cholesterol absorption inhibitor ezetimibe, in addition to background statin treatment.
Background high intensity statin treatment did not influence the LDL-c lowering response to alirocumab. The least square mean reduction in LDL-c ranged from 47 to 62% reduction on high intensity statin treatment versus 35 to 61% in those not on high-intensity statin therapy. In the largest trial in this analysis, ODYSSEY LONG TERM (n=2310 patients), treatment with alirocumab reduced LDL-c by 62% in patients on high intensity statin therapy compared with 61% in patients who were not.
A separate analysis evaluated LDL-c goal attainment in eight Phase 3 trials in patients at high cardiovascular risk on statin treatment with or without other lipid-lowering therapy. 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-c levels were above guideline-recommended LDL-c goal at week 8, or 150 mg every 2 weeks), placebo or ezetimibe. At week 24, alirocumab reduced LDL-c from baseline by 49% (75/150 mg every 2 weeks) and by 60% with 150 mg every 2 weeks (p<0.0001). Across the trials, 75-79% of patients achieved LDL-c 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.
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-c targets despite best treatment including high intensity statins.
In an analysis of six alirocumab trials involving more than 4000 patients, lowering of LDL-c with this PCSK9 antibody was not influenced by background high intensity statin therapy.
It is well known that statins increase plasma PCSK9 concentration, which could potentially reduce the efficacy of PCSK9 inhibitors. This hypothesis was tested in an analysis of 4166 patients receiving background treatment with a maximally tolerated dose of high intensity statin or non-high intensity statin. Five trials also allowed for non-statin lipid-lowering treatment. All patients were at high cardiovascular risk (18% with heterozygous familial hypercholesterolaemia). Patients received alirocumab injection (75 mg increasing to 150 mg every 2 weeks if the LDL-c goal was not achieved, or 150 mg every-2 weeks), placebo or the cholesterol absorption inhibitor ezetimibe, in addition to background statin treatment.
Background high intensity statin treatment did not influence the LDL-c lowering response to alirocumab. The least square mean reduction in LDL-c ranged from 47 to 62% reduction on high intensity statin treatment versus 35 to 61% in those not on high-intensity statin therapy. In the largest trial in this analysis, ODYSSEY LONG TERM (n=2310 patients), treatment with alirocumab reduced LDL-c by 62% in patients on high intensity statin therapy compared with 61% in patients who were not.
A separate analysis evaluated LDL-c goal attainment in eight Phase 3 trials in patients at high cardiovascular risk on statin treatment with or without other lipid-lowering therapy. 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-c levels were above guideline-recommended LDL-c goal at week 8, or 150 mg every 2 weeks), placebo or ezetimibe. At week 24, alirocumab reduced LDL-c from baseline by 49% (75/150 mg every 2 weeks) and by 60% with 150 mg every 2 weeks (p<0.0001). Across the trials, 75-79% of patients achieved LDL-c 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.
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-c targets despite best treatment including high intensity statins.