There is currently NO oral PCSK9 inhibitor available for clinical use
All currently approved PCSK9 inhibitors (alirocumab and evolocumab) are administered subcutaneously, not orally. 1, 2, 1
Currently Available PCSK9 Inhibitors
Approved Injectable Formulations
Alirocumab:
- 75 mg or 150 mg subcutaneously every 2 weeks
- Alternative: 300 mg subcutaneously every month
- LDL-C reduction: 50-60% 1
Evolocumab:
- 140 mg subcutaneously every 2 weeks
- Alternative: 420 mg subcutaneously every month
- LDL-C reduction: approximately 53-60% 1, 3
Clinical Efficacy
Both agents demonstrated cardiovascular benefit in major outcome trials:
- FOURIER trial (evolocumab): 15% relative risk reduction in cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization 2, 1
- ODYSSEY Outcomes trial (alirocumab): 15% reduction in coronary heart disease death, nonfatal MI, stroke, or unstable angina requiring hospitalization 1
Both achieved median LDL-C levels around 0.78-0.9 mmol/L (30-35 mg/dL) when added to statin therapy 1, 3
Safety Profile
- Well tolerated with adverse event profile similar to placebo 1, 3
- Injection site reactions: relatively infrequent and mild 3
- No excess adverse events even with LDL-C <0.65 mmol/L (<25 mg/dL) 3
- Muscle-related adverse events comparable to ezetimibe in statin-intolerant patients 3
Clinical Indications
PCSK9 inhibitors should be considered for:
- Patients with familial hypercholesterolemia not achieving LDL-C targets despite maximally tolerated statin ± ezetimibe 1
- Very high-risk patients with established ASCVD and LDL-C ≥100 mg/dL (2.6 mmol/L) despite maximal statin and ezetimibe therapy 2, 4
- Statin-intolerant patients requiring additional LDL-C lowering beyond ezetimibe 2
Important caveat: There are currently no RCT data supporting PCSK9 inhibitor use for primary prevention in patients without established ASCVD or familial hypercholesterolemia 2