It’s no secret a lot of patients do not tolerate statin drugs. They have side effects that just can’t be eliminated. There are also a lot of folks who, despite maximum lipid-lowering therapy, still have an elevated LDL-C. Then there is a third group of patients whose cardiovascular disease worsens in spite of their lipids being at target levels. Something about the third group is eluding researchers trying to find an agent that will prevent secondary events (heart attack, stroke, CAD) from happening.
A relatively new class of drugs called PCSK9 monoclonal antibodies has been studied extensively comparing them to placebo, statins, and ezetimibe (Zetia). The acronym just mentioned stands for Proprotein convertase subtilisin/kexin type 9. It’s a class of monoclonal antibody drugs that lower cholesterol via a different mechanism than statins. The two PCSK9 drugs currently available are alirocumab (Praluent) and evolocumab (Repatha).
Twenty-four studies were reviewed for this report. Half (12) compared Praluent to placebo. Six compared Praluent to statins and ezetimibe. Three compared Repatha to placebo, and three compared Repatha to statins and ezetimibe. All of the patients in the study had known CVD and had a previous heart attack, stroke, or coronary artery disease.
Here are the results of the analysis:
Compared to placebo, Praluent decreased the risk of CVD events, all cause mortality, heart attack, and stroke.
Compared to statins and ezetimibe, Praluent did not show any difference in CVD, all cause mortality, heart attack, and stroke.
Compared to placebo, Repatha decreased the risk of CVD events, heart attack, stroke, and showed no difference in all cause mortality.
Compared to statins and ezetimibe, Repatha showed no difference in CVD events, all cause mortality, heart attack and stroke.
These studies show there may be a place for prescribing PCSK9 inhibitors (Praluent, Repatha) in patients who do not respond to or cannot tolerate statins or other lipid-lowering drugs. PCSK9 drugs are not superior to statins and ezetimibe, but they work just as well when compared to placebo, making them a good alternative to statins.
The American College of Cardiology/American Heart Association guidelines recommend PCSK9 inhibitors for secondary prevention (treatment of patients know to have vascular disease) in patients with a high LDL-C despite effective statin levels and/or folks unable to tolerate statins. It is recommended for risk reduction in patients who are diabetic, have ASCVD, or need more effective lowering of LDL-C.
PCSK9 monoclonal antibodies are effective in patients with known ASCVD as well as those without. But when added to optimal lipid therapy, they reduced heart attack and stroke only a little. Their niche seems to be more for patients who do not respond or can’t tolerate statins.
A huge negative with PCSK9 inhibitors is the high cost. Praluent runs $6000 a year while Repatha is $3000 annually. Generic Lipitor (atorvastatin) runs $240/year. These drugs should be used in dire situations only, but do remain an option to be considered.
References: Youssek E, Olson J, Kalantari H. PCSK9 Monoclonal Antibodies for Primary and Secondary Prevention of CVD. Am Fam Phys 2026 August; 114(2):126-127. .
