2017 NLA guidelines: PCSK9 inhibition and cholesterol

PCSK9 inhibitors are a relatively new class of medications. They lower atherogenic cholesterol and cardiovascular disease significantly. Although effective, cost limits their use to persons at high risk for CVD in spite of being optimally manged with statins (mainly crestor or lipitor).

National Lipid Association recently published the updated guidelines on the use of PCSK9 inhibitors in patients with residual CVD risk, very high LDL-cholesterol and those with intolerance to statin therapy. Recommendations are listed below with slightly modified wording for easier and succinct reading:

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J of Clinical Lipidology

Guidelines

August 2017

 

NEW: 2017 NLA Recommendations:

 

(1) Patients with established ASCVD:

1a. PCSK9 inhibitor therapy should be considered for ASCVD risk reduction in patients with stable atherosclerotic cardiovascular disease, particularly in those with additional ASCVD risk factors, on maximally-tolerated statin therapy ± ezetimibe, with on-treatment LDL-C ≥70 mg/dL or non–HDL-C ≥100 mg/dL. 

1b. PCSK9 inhibitor therapy may be considered to further reduce LDL-C in patients with progressive atherosclerotic cardiovascular disease on maximally-tolerated statin therapy ± ezetimibe, and on-treatment LDL-C ≥70 mg/dL or non–HDL-C ≥100 mg/dL.

 

(2) Patients with pre-treatment LDL-C ≥ 190 mg/dL

Polygenic hypercholesterolemia, heterozygous FH and the homozygous FH phenotype:

2a [older, less risk factors].  PCSK9 inhibitor therapy may be considered to further reduce LDL-C in patients ages 40-80 years with pre-treatment LDL-C ≥ 190 mg/dL, no uncontrolled ASCVD risk factors, or other key additional high-risk markers, and on-treatment LDL-C ≥100 mg/dL or non–HDL-C ≥130 mg/dL on maximally-tolerated statin therapy ± ezetimibe.

2b [older, more risk factors].  PCSK9 inhibitor therapy may be considered to further reduce LDL-C in patients aged 40-80 years with pre-treatment LDL-C ≥ 190 mg/dL, and the presence of either uncontrolled ASCVD risk factors, key additional high-risk markers, or genetic confirmation of FH, and on-treatment LDL-C ≥70 mg/dL or non–HDL-C ≥100 mg/dL on maximally-tolerated statin ± ezetimibe. 

2c [younger, more risk factors].  PCSK9 inhibitor therapy may be considered to further reduce LDL-C in patients aged 18-40 years with pre-treatment LDL-C ≥ 190 mg/dL, and the presence of either uncontrolled ASCVD risk factors, key additional high-risk markers, or genetic confirmation of FH, and on-treatment LDL-C ≥100 mg/dL or non–HDL-C ≥130 mg/dL on maximally-tolerated statin ± ezetimibe.

2d. [homozygous FH = high risk] PCSK9 inhibitor therapy may be considered to further reduce LDL-C in patients with homozygous familial hypercholesterolemia, either of unknown genotype, or those known to be LDL receptor defective, on maximally-tolerated statin therapy ± ezetimibe with LDL-C ≥70 mg/dL or non–HDL-C ≥100 mg/dL.

 

(3) Very-high-risk/statin intolerance:

PCSK9 inhibitor therapy may be considered to further reduce LDL-C in selected very-high-risk patients who meet the definition of statin intolerance (as previously defined by the NLA Statin Expert Panel) and who require substantial additional atherogenic cholesterol lowering, despite the use of other lipid-lowering therapies. 


 

OLD: 2015 NLA Part II recommendations:

1. Until cardiovascular outcomes trials are completed with PCSK9 inhibitors, these drugs should be considered primarily in

(a) Patients with ASCVD who have LDL-C ≥ 100 mg/dL (non–HDL-C ≥130 mg/dL) while on maximally tolerated statin (±ezetimibe) therapy; and

(b) Heterozygous hypercholesterolemia (FH) patients without ASCVD who have LDL-C ≥130 mg/dL (non–HDL-C ≥160 mg/dL) while on maximally tolerated statin (±ezetimibe) therapy. 

2. PCSK9 inhibitor use may be considered for selected high-risk patients with ASCVD (eg, recurrent ASCVD events) who have atherogenic cholesterol levels below the specified values, but above their treatment goals (ie, LDL-C ≥ 70 mg/dL [non–HDL-C ≥100 mg/dL]).

Such use would be based on clinical judgment, weighing the potential benefits relative to the ASCVD event risk and the risks and costs of therapy.

3. PCSK9 inhibitor use may also be considered in selected high or very-high-risk patients who meet the definition of statin intolerance and who require substantial additional atherogenic cholesterol lowering, despite the use of other lipid-lowering therapies.

Such use would be based on clinical judgment, weighing the potential benefits relative to the ASCVD event risk and the risks and costs of therapy.