Dyslipidaemia

Principles

  • Principles: Higher LDL-c levels increase risk of CVD and reduction diminishes this risk (see table below for drugs used on this indication); the reverse is probably true for HDL-c but trial data are less compelling. The CVD risk implications from higher than normal TG levels are even less clear, as TG has not consistently been shown to independently predict the risk of CVD
  • Furthermore, the clinical benefit of treating moderate hypertriglyceridaemia is uncertain; very high TG (> 10 mmol/L or > 900 mg/dL) increase risk of pancreatitis
  • Less calories, more exercise, reducing bodyweight, and stopping smoking tend to improve (increase) HDL. Eating fish, reducing calories, saturated fat and alcohol intake reduce triglyceride levels. Reducing dietary saturated fat intake improves LDL-levels; if not effective, consider change of ART, then consider lipid-lowering medicine, see Prevention of CVD. Statins should be used by all those with established vascular disease and among those with type 2 diabetes or at high risk of CVD, irrespective of lipid levels

Drugs used to lower LDL-c

Drug class

Drug

Dose

Side effects

Advise on use of statin together with ART

use with PI/r

use with NNRTIs

Statin(i,ix)

atorvastatin(ii)

10-80 mg qd

Gastrointestinal symptoms, headache, insomnia, rhabdomyolysis (rare) and toxic hepatitis

Start with low dose(v) (max: 40 mg)

Consider higher dose(vi)

fluvastatin(iii)

20-80 mg qd

Consider higher dose(vi)

Consider higher dose(vi)

pravastatin(iii)

20-80 mg qd

Consider higher dose(vi,vii)

Consider higher dose(vi)

rosuvastatin(ii)

5-40 mg qd

Start with low dose(v) (max: 20 mg)

Start with low dose(v)

simvastatin(ii)

10-40 mg qd

Contraindicated

 

Intestinal cholesterol absorption inhibitor↓(i,viii)

ezetimibe(iv)

10 mg qd

Gastrointestinal symptoms

No known drug-drug interactions with ART

PCSK9-inhibitor(x)

evolocumab

140 mg 2 weekly or 420 mg monthly

Nil

No drug-drug interactions anticipated

 

i A statin is preferred first-line therapy; different statins have variable intrinsic LDL-c lowering ability
ii, iii, iv Target levels for LDL-c, see Prevention of Cardiovascular Disease (CVD). In PLWH where LDL-c targets are difficult to achieve, consult/refer to specialist
Expected range of reductions of LDL-c: ii 1.5-2.5 mmol/L (60-100 mg/dL), iii 0.8-1.5 mmol/L (35-60 mg/dL), iv 0.2-0.5 mmol/L (10-20 mg/dL)
v, vi The ARV may v inhibit (statin toxicity, ↓ dose) or vi induce (= less effect of statin, ↑ dose gradually to achieve expected benefit ii, iii) the excretion of the statin
vii Exception: If used with DRV/r, start with lower dose of pravastatin
viii This agent can be used for PLWH intolerant of statins or added to a statin when LDL reduction is inadequate despite maximally tolerated statin
ix Pitavastatin has as yet no morbidity/mortality trial data to support its use but may have advantages of reducing immune activation and arterial inflammation, fewer drug-drug interactions, more HDL increase and less adverse glucose effect than other statins
x Consider for highest risk individuals inadequately controlled on top statin dose or for statin intolerant individuals