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Dyslipidaemia

Principles

Higher LDL-c levels increase risk of CVD and reduction diminishes this risk (see table below for drugs used on this indication). For triglycerides (TG), there is no goal, but < 1.7 mmol/L (< 150 mg/dL) indicates lower risk and higher levels indicate a need to look for other risk factors. Statin treatment is recommended as the first drug of choice to reduce CVD risk in high-risk individuals with hypertriglyceridemia [TG > 2.3 mmol/L (> 200 mg/dL)]. Confirmation of hypertriglyceridemia needs to be verified with fasting lipid testing. Very high TG (> 10 mmol/L or > 900 mg/dL) increase risk of pancreatitis, fibrates should be used. Lipids testing should be performed every year in high or very high risk subjects and every 3-5 years in low and moderate risk subjects.

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 Cardiovascular Disease (CVD).

Statins should be used by all those with established vascular disease and in persons who are not at LDL-c goals considering their level of CVD risk, irrespective of lipid levels, see Treatment Goals for LDL-c to Reduce Cardiovascular Risk in Individuals with High and Very High Cardiovascular Disease Risk. In individuals at high-risk of CVD with statin intolerance, drug-drug interactions between high-intensity statins and ART, or those unable to reach LDL-c goals on statins and/or ezetimibe, bempedoic acid and/or a PCSK9 inhibitor should be considered. Icosapent ethyl (EPA) should be discussed in adjunct to statin in very high risk patients (post MI and diabetics with another CV risk factor with TGs > 150mg/dL or > 1.7 mmol/L.

Drugs used to reduce cardiovascular risk by lowering LDL-c and triglycerides

Drug class

Drug

Dose

Adverse effects

Advice on use of lipid lowering therapy together with ART

use with PI/r

use with NNRTIs

Statin(i, viii)

atorvastatin(ii)

10-80 mg qd

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

Start with low dose(v) (max daily dose: 10 mg (ATV/r); 20 mg (LPV/r); 40 mg (DRV/r)

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 daily dose: 10 mg (ATV/r, LPV/r) 20 mg (DRV/r)

Start with low dose(v)

simvastatin(ii)

10-40 mg qd

Contraindicated

 

pitavastatin(viii)

1-4 mg qd

No interaction expected

Adenosine triphosphate citrate lyase inhibitor*

Bempedoic acid

180 mg qd

Gout, cholelithiasis

No interaction expected.
Contraindicated with simvastatin > 40mg qd

Intestinal cholesterol absorption inhibitor↓(i,viii)

ezetimibe(iv)

10 mg qd

Gastrointestinal symptoms

No interaction expected

PCSK9-inhibitors(x) 

alirocumab

75 mg or 150 mg 2 weekly or 300 mg monthly

Nil

 

No interaction expected

 

 

evolocumab

140 mg 2 weekly or 420 mg monthly

inclisiran  284 mg once and repeat in 3 months. Maintenance dose 284 mg every 6 months
Fish oil, Omega-3

Icosapent ethyl(xi)

2 g bid

Atrial fibrillation, bleeding

No interaction expected

 

  1. A statin is preferred first-line therapy; different statins have variable intrinsic LDL-c lowering ability
  2. Target levels for LDL-c, see Prevention of Cardiovascular Disease (CVD). In persons where LDL-c targets are difficult to achieve, consult/refer to specialist. Expected range of reductions of LDL-c: 1.5-2.5 mmol/L (60-100 mg/dL)
  3. Target levels for LDL-c, see Prevention of Cardiovascular Disease (CVD). In persons where LDL-c targets are difficult to achieve, consult/refer to specialist. Expected range of reductions of LDL-c: 0.8-1.5 mmol/L (35-60 mg/dL)
  4. Target levels for LDL-c, see Prevention of Cardiovascular Disease (CVD). In persons where LDL-c targets are difficult to achieve, consult/refer to specialist. Expected range of reductions of LDL-c: 0.2-0.5 mmol/L (10-20 mg/dL)
  5. The ARV may inhibit (statin toxicity, ↓ dose) the excretion of the statin
  6. The ARV may induce (= less effect of statin, ↑ dose gradually to achieve expected benefit ii, iii) the excretion of the statin
  7. Exception: If used with DRV/r, start with lower dose of pravastatin
  8. 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
  9. This agent can be used for persons intolerant of statins or added to a statin when LDL-c reduction is inadequate despite maximally tolerated statin
  10. Data in persons with HIV available for evolocumab
  11. Icosapent ethyl, a pure ester of eicosapentaenoic acid (EPA) from the omega-3 family, is indicated to reduce cardiovascular risk as an adjunct to statin therapy in subjects with myocardial infarction and/or people with diabetes at high cardiovascular disease risk with elevated triglycerides (< 10mg:dL or 1.7 mmol/L).