From the Guidelines
PSK9 inhibitors are recommended over statins for patients with high-risk cardiovascular disease or familial hypercholesterolemia who require additional lowering of LDL cholesterol beyond maximally tolerated statin therapy, as they have been shown to reduce LDL cholesterol by 36-59% and decrease ASCVD outcomes. When considering the treatment of high cholesterol, it's essential to weigh the benefits and risks of each medication class. Statins, such as atorvastatin and rosuvastatin, are the first-line treatment for high cholesterol, reducing LDL cholesterol by 30-50% 1. However, for patients who cannot reach their LDL goals with statins alone or have familial hypercholesterolemia, PSK9 inhibitors, like evolocumab and alirocumab, can lower LDL cholesterol by an additional 50-70% beyond statins 1.
Some key points to consider when prescribing PSK9 inhibitors include:
- They are typically reserved for patients with high-risk cardiovascular disease or familial hypercholesterolemia who require aggressive LDL lowering
- They are given as subcutaneous injections every 2-4 weeks, with evolocumab dosed at 140mg every 2 weeks or 420mg monthly 1
- They are significantly more expensive than statins and often require insurance approval
- The FOURIER trial demonstrated that evolocumab reduced LDL cholesterol by 59% and decreased ASCVD outcomes in patients with prior ASCVD and high-risk features 1
In clinical practice, the decision to use PSK9 inhibitors over statins should be based on the individual patient's risk profile and ability to tolerate statin therapy. The use of PSK9 inhibitors as adjunctive therapy to maximally tolerated statin therapy can provide significant reductions in LDL cholesterol and ASCVD outcomes, making them a valuable treatment option for high-risk patients.
From the Research
Comparison of PSK9 Inhibitors and Statins
- PSK9 inhibitors, such as evolocumab and alirocumab, are monoclonal antibodies that inactivate the liver proprotein convertase subtilisin kexin 9 (PCSK9), leading to a profound reduction in circulating LDL particles 2.
- Statins, on the other hand, are a class of drugs that inhibit the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver 3.
- The combination of PSK9 inhibitors with statins has been shown to reduce LDL-C levels by 50-60% above that achieved by statin therapy alone, and may reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD 2.
Efficacy and Safety
- A systematic network meta-analysis found that PSK9 inhibitors and potent statins significantly reduced LDL-C levels from baseline vs. placebo, regardless of background therapy 4.
- The combination of PSK9 inhibitors with robust statins like rosuvastatin and atorvastatin markedly decreases LDL-C levels in patients with hyperlipidemia when compared to placebo or monotherapy 4.
- The incidence of adverse events was similar to that observed in the control group, with no significant differences identified 4.
Clinical Guidelines
- The 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend the use of PSK9 inhibitors in very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 2.
- The US Preventive Services Task Force (USPSTF) recommends that clinicians prescribe a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more CVD risk factors and an estimated 10-year CVD risk of 10% or greater 5.
- The USPSTF also recommends that clinicians selectively offer a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more of these CVD risk factors and an estimated 10-year CVD risk of 7.5% to less than 10% 5.