Table 1. Summary of important study findings on the safety and efficacy of evolocumab and alirocumab.

PCSK9: proprotein convertase subtilisin/kexin type 9; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; ASCVD: atherosclerotic cardiovascular diseases

Study	Key findings	Importance
Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolemia (MENDEL): a randomized, double-blind, placebo-controlled, phase 2 study [9]	Evolocumab caused a significant dose-dependent decrease in LDL-C levels from baseline at week 12, along with notable reductions in free PCSK9 levels, and a minor decrease in triglyceride levels. A significant increase in HDL-C levels was observed in the evolocumab patients	The data from this study became the basis of the phase 3 MENDEL-2 study evaluating the long-term safety and efficacy of evolocumab in a more diverse population with a history of statin intolerance
Monoclonal antibody against PCSK9 to reduce elevated LDL-C in subjects currently not receiving drug therapy for easing lipid levels-2 (MENDEL-II) [23]	55% reduction in LDL-C levels from baseline after 12 weeks of evolocumab as a monthly monotherapy. 57% reduction in LDL-C levels from baseline when evolocumab was administered weekly	Largest monotherapy trial where evolocumab was found to be well-tolerated and caused significant LDL-C reductions versus ezetimibe or placebo
A 52-week placebo-controlled trial of evolocumab in hyperlipidemia: the durable effect of PCSK9 antibody compared with placebo study (DESCARTES) [27]	In the evolocumab group, at 52 weeks, LDL-C levels were reduced by 57.0 ±2.1% (p<0.001). Evolocumab significantly reduced levels of apolipoprotein B, non-HDL cholesterol, lipoprotein (a), and triglycerides	Evolocumab caused significant LDL-C reduction in patients on statin therapy who were at risk for coronary diseases
Efficacy and safety of evolocumab in reducing lipids and cardiovascular events: the open-label study of long-term evaluation against LDL cholesterol (OSLER) I and II studies [28]	Evolocumab reduced the LDL-C levels from a baseline of 120 mg/dL to 48 mg/dL. Years 2-5 of treatment with evolocumab showed lower instances of injection-site reactions versus year 1	The longest trial evaluating the use of PCSK9 inhibitor antibodies. Findings indicated the long-term safety and efficacy of evolocumab [30]
Efficacy and safety of alirocumab in reducing lipids and cardiovascular events: the ODYSSEY LONG TERM trial [25]	Alirocumab caused a 62% reduction in LDL-C levels at week 24 compared to placebo. Post hoc analysis observed lower rates of major cardiovascular events with alirocumab	Consistent reductions in LDL-C levels were seen with alirocumab over 78 weeks, along with a reduction in cardiovascular events in patients on maximally tolerated statin doses
A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I [22]	52% reduction in LDL-C levels from baseline after 24 weeks of a 300m g dose of alirocumab administered every 4 weeks	Alirocumab 300 mg Q4 weeks may be a useful therapeutic choice with or without statins in patients who need additional options for LDL-C lowering
Evolocumab and clinical outcomes in patients with cardiovascular disease: the FOURIER trial [31]	A 62% reduction in LDL-C levels was observed in 59% of the evolocumab patients. In patients on statin therapy, PCSK9 inhibition from evolocumab reduced LDL-C levels to a median of 30 mg/dL. A significant reduction was observed in the primary composite endpoint for components of myocardial infarction, stroke, and coronary revascularization	Patients with ASCVD benefit from LDL-C reductions below current targets
Alirocumab and cardiovascular outcomes after acute coronary syndrome: the ODYSSEY OUTCOMES trial [32]	Patients with baseline LDL-C levels ≥100 mg/dL showed a greater benefit with alirocumab in terms of the composite primary endpoint of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization	Alirocumab was associated with a lower risk of recurrent ischemic cardiovascular events versus placebo when administered to patients with a history of acute coronary syndrome and on a high-intensity statin regimen
Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study [33]	At week 24, 75% of the alirocumab group patients achieved LDL levels <70 mg/dL	At 24 weeks, alirocumab therapy led to a higher proportion of patients attaining their target LDL-C levels with inadequately controlled hypercholesterolemia despite maximally tolerated statin therapy with or without additional lipid-lowering treatment choices
Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial [34]	At week 24, 77% of patients on alirocumab achieved LDL-C levels <1.8 mmol/L	Alirocumab was found to be well-tolerated and caused notably higher reductions in LDL-C levels versus ezetimibe in patients on statin therapy