PCSK9 Inhibitors: Where do we Stand and How Does it Change Practice?

Statin therapy has revolutionized the field of cardiovascular prevention and has greatly reduced morbidity and mortality in secondary and primary prevention. However, despite statins, residual risk is still substantial and a sizable proportion of patients are unable to tolerate high dose statins. It is therefore of importance that new targets have been identified to further lower LDL cholesterol.

PCSK9 inhibitors offer dramatic reductions of LDL cholesterol levels beyond those achievable with statins. Multiple studies showed 40-60% reductions in LDL levels with these agents beyond maximally tolerated statins and initial experience suggests the agents are generally safe during short time exposure.

The recently published FOURIER study examined the role of evolucomab, one of the 2 commercially available PCSK9 inhibitors, to reduce cardiovascular (CV) risk beyond statins in secondary prevention. The results showed significant reductions of the composite of CV death, MI, stroke, hosp. for UA, or coronary revascularization, as well as the composite of: CV death, MI or stroke. Cardiovascular or overall mortality were not significantly reduced. Treatment was generally safe and a neurocognitive substudy was also negative. The results of the ODYSSEY OUTCOMES trial with alirocumab will be published in early 2018 and will provide further insight into this treatment among higher risk patients.

At this time PCSK9 inhibitors have been clearly shown to reduce LDL levels dramatically and to reduce composite ischemic outcomes significantly. Longer follow up and additional studies will be needed to better appreciate the long term efficacy and safety of these agents. The high of PCSK9 inhibitors will require careful consideration of the most appropriate patient subgroups in whom this therapy will be justified.