Recommendation 1
We recommend ezetimibe as second-line therapy to lower LDL-C in patients with clinical cardiovascular disease if targets are not reached on maximally tolerated statin therapy (Strong Recommendation, High Quality Evidence).

Recommendation 2
We recommend that niacin not be added to statin therapy for CVD prevention in patients who have achieved LDL-C targets (Strong Recommendation, High Quality Evidence).

Values and Preferences
It remains unclear whether niacin offers CV benefits in other patient groups, such as those with LDL-C above target or those with low HDL-C or high TG.

Recommendation 3
We recommend that fibrates not be added to statin therapy for CVD event prevention in patients who have achieved LDL-C targets (Strong recommendation, High Quality evidence).

Values and preferences
In sub-group analysis, patients with elevated triglycerides and low HDL-C may benefit from fibrate therapy.

Recommendation 4
We suggest that bile acid sequestrants be considered for LDL-C lowering in high risk patients who remain above target despite statin +/- ezetimibe therapy (Conditional Recommendation, Low Quality Evidence).

Recommendation 5
We suggest the use of PCSK9 inhibitors (evolocumab, alirocumab) to lower LDL-C for patients with heterozygous familial hypercholesterolemia whose LDL-C remains above target despite maximally tolerated statin therapy (Conditional Recommendation, Moderate Quality Evidence). We suggest that Evolocumab be added to background therapy in patients with homozygous familial hypercholesterolemia and continued if LDL-C lowering is documented (Conditional Recommendation, Moderate Quality Evidence).

Recommendation 6
We suggest that PCSK9 inhibitors be considered to lower LDL-C for patients with atherosclerotic cardiovascular disease in those not at LDL-C goal despite maximally tolerated statin +/- ezetimibe therapy (Conditional Recommendation, Moderate Quality Evidence).

Values and preferences
Definitive outcome trials with PCSK9 inhibitors are underway but have not yet been completed. However, phase 3 efficacy trials show consistent reduction in LDL-C and reassuring trends towards reduced CV events, even though not powered for such. Given the very high lifetime risk faced by patients with FH or ASCVD, clinicians should balance the anticipated benefits of robust LDL –C lowering with PCSK9 inhibitors against the lack of definitive outcomes data.

Recommendation 7
We suggest lomitapide and mipomersen* may be considered exclusively in patients with homozygous familial hypercholesterolemia (Conditional Recommendation, Moderate Quality Evidence). * not approved in Canada