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HYPERLIPIDEMIA: LDL / ASCVD / or ASCVD Risk score - Moderate / High dose statin or no treatment

Statin in Primary Prevention 
  • JUPITER NEJM 2008; Rosuvastatin in patients with high CRP but LDL below the goal hence these are patient at intermediate risk patients 
  • ENHANCE NEJM 2008 (Simva + Ezitemibe in Familial Hypercholesterolemia)
  • HOPE 3 (Intermediate Risk Patient) 
    • Cholesterol control only arm NEJM 2016 (CRP level for inclusion criteria was higher in JUPITER trial; In this study, CRP level was not used at all for inclusion and exclusion criteria and no difference was seen among patients with > 2 or < 2 CRP, the cutoff value used in the JUPITER trial) 
    • Cholesterol and BP control arm NEJM 2016
  • Lipid Management in CKD: Please see CKD under Nephrology 
Statin in Secondary Secondary Prevention
  • Stroke Prevention: 
    • SPARCL NEJM 2006
  • Stable CAD: 
    • AIM-HIGN NEJM 2011
  • ACS:
    • PROVE-IT NEJM 2004
    • MIRACL JAMA 2011
    • IMPROVE-IT NEJM 2015
  • Lipid Management in CKD: Please see CKD under Nephrology (This probably falls in Primary Prevention than Secondary Prevention) 
Stroke Prevention 

Stable CAD



Ezetimibe targets the Niemann–Pick C1–like 1 (NPC1L1) protein, thereby reducing absorption of cholesterol from the intestine 

Statin in Primary Prevention 
  • JUPITER NEJM 2008 
  • HOPE 3 
    • Cholesterol control only arm NEJM 2016
    • Cholesterol and BP control arm NEJM 2016
Rosuvastatin in patients with high CRP but at LDL below the recommended treatment; Intermediate Risk patients 
This trial was stopped early due to positive outcome 



Summary of HOPE 3: 
  • If BP> 144: Both BP lowering medications, and Statin are of useful. 
  • If BP< 144: Only Statin may be of use irrespective of Cholesterol level. Bottom Line Statin are of useful in Primary Prevention of CV risks. 
  • More HOPE for Prevention with Statins NEJM Editorial 2016 
    • This trial reinforces the use of Statin based on Risk Factors as mentioned in the current guidelines, and not based on LDL (that was again in conversation after IMPROVE- IT trial)
    • There was difference in patient with CRP > 2 vs < 2 (as used in JUPITER NEJM 2008). Hence, probably no need to check CRP in deciding whom to treat and not to treat. 
    • However, my personal comment on this is: 
      • For secondary prevention, target matters, and they need to be on moderate-to-potent statin. But, for primary prevention, treatment can be started on the basis of risk, and LDL level may be checked. But, we have not had study yet on Rosuvastatin at 20 mg or 40 mg (Mod-high potency dose), which means if further drop in LDL will add to the benefit is not known. There is every possibility that Statin of lower level in these intermediate risk patients, may provide additional benefit. If that were to be found, then it would argue for LDL level hypothesis. 
      • Bottom line so far: 
        • Primary Prevention: Start based on risk factors. No need to check LDL in intermediate risk patients. Can aim for LDL level in high risk patients. 
        • Secondary prevention: Aim for lower LDL. Ofcourse, we have started the statin based on risk factors, which is highest for these patients. 

Statins seem to have multiple non-cardiovascular effects. 

  • Although early concerns about statin induced hepatotoxicity and cancer have subsided owing to reassuring evidence, two of the most common concerns that clinicians have are 
    • Myopathy: Randomized controlled trials suggest that statins are associated with a modest increase in the risk of myositis but not the risk of myalgia. Severe myopathy (rhabdomyolysis) is rare and often linked to a statin regimen that is no longer recommended (simvastatin 80 mg). 
    • Diabetes. Randomized controlled trials and meta-analyses suggest an increase in the risk of diabetes with statins, particularly with higher intensity regimens in people with two or more components of the metabolic syndrome. 
    • Contrast induced nephropathy, 
    • cognition, 
    • cataracts, 
    • erectile dysfunction, and 
    • venous thromboembolism.