Treatment adherence and effect of concurrent statin intensity on the efficacy and safety of alirocumab in a real-life setting: results from ODYSSEY APPRISE

Abstract

Introduction: The phase IIIb open-label ODYSSEY APPRISE study prospectively assessed the safety and efficacy of alirocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in a real-life setting in high cardiovascular risk patients with heterozygous familial hypercholesterolemia or low-density lipoprotein cholesterol (LDL-C) not at goal despite maximally tolerated dose statins ± other lipid-lowering therapies (NCT02476006). This post-hoc analysis assessed patient adherence to statins and alirocumab, plus alirocumab efficacy and safety, according to concomitant statin intensity and prior ezetimibe usage.

Material and methods: Patients received alirocumab 75 or 150 mg (dose adjustment based on physician's judgment) every 2 weeks (for ≥ 3 to ≤ 30 months).

Results: Of 994 enrolled and treated patients, 58.4% received concomitant high-intensity statins, 18.2% received moderate/low-intensity statins, and 23.4% received no statin; 55.9% received prior ezetimibe. Mean alirocumab adherence (percent adherence defined as injections received/theoretical injections × 100) was 96.6% over 72.4 weeks' mean treatment duration. Mean LDL-C reduction from baseline at Week 12 was similar between statin intensity subgroups (53.6-55.7%). More patients achieved LDL-C < 1.8 mmol/l and/or ≥ 50% reduction from baseline in the ≥ 100% versus < 100% adherent to alirocumab subgroup; high-intensity and low/moderate-intensity subgroups versus no statin subgroup; and prior ezetimibe versus no prior ezetimibe subgroup. Treatment-emergent adverse events occurred in 65.2-75.1% and 68.0-76.3% of patients across statin and ezetimibe subgroups, respectively.

Conclusions: In a real-life setting, patient adherence to alirocumab was high. Alirocumab provided clinically significant reductions in LDL-C, with most patients achieving LDL-C treatment targets across background statin therapy and prior ezetimibe therapy subgroups.

Keywords: PCSK9; cholesterol; low-density lipoprotein; treatment adherence.

Figure 1

Proportion of patients achieving LDL-C goals at Week 12 on alirocumab treatment. A – According to adherence to alirocumab. B – Both overall and according to background statin intensity*. C – According to prior ezetimibe medication (mITT population) *High-intensity statin was defined as atorvastatin 40 or 80 mg, rosuvastatin 20 or 40 mg, or simvastatin 80 mg daily; low/moderate-intensity statin was defined as all other statins and/or doses. LDL-C – low-density lipoprotein cholesterol, mITT – modified intention-totreat.

Figure 2

Proportion of patients achieving LDL-C goals. A – Week 24. B – Week 48, according to adherence to alirocumab* (mITT population) *Adherence to alirocumab treatment was assessed according to patients’ diary data over the duration of the trial; percent adherence was defined as the number of injections received divided by the number of theoretical injections to be received during the study period multiplied by 100, with the number of theoretical injections defined as the last injection date minus the first injection date divided by 14. LDL-C – low-density lipoprotein cholesterol, mITT – modified intention-to-treat.

Figure 3

Proportion of patients achieving LDL-C goals. A – Week 24. B – Week 48, according to prior ezetimibe medication (mITT population) LDL-C – low-density lipoprotein cholesterol, mITT – modified intention-to-treat.