Initiating Statin therapy : What all to be considered

Statins are backbone for treatment of Dyslipedemia but before initiating Statins ,clinicians must first determine the patient’s risk of having a future CVD event, in order to determine whether a patient is a candidate for statin therapy or not. The USPSTF has made several recommendations for Statin Use for the Primary Prevention of Cardiovascular Disease in Adults which are as follows.

1.Adults aged 40 to 75 years with no history of CVD, 1 or more CVD risk factors, and a calculated 10-year CVD event risk of 10% or greater-

The recommendations of USPSTF are that adults without a history of cardiovascular disease (CVD) (ie, symptomatic coronary artery disease or ischemic stroke) use a low- to moderate-dose statin for the prevention of CVD events and mortality when all of the following criteria are met: 1) they are aged 40 to 75 years; 2) they have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking); and 3) they have a calculated 10-year risk of a cardiovascular event of 10% or greater. Identification of dyslipidemia and calculation of 10-year CVD event risk requires universal lipids screening in adults aged 40 to 75 years.

2.Adults aged 40 to 75 years with no history of CVD, 1 or more CVD risk factors, and a calculated 10-year CVD event risk of 7.5% to 10%-

The recommendations of USPSTF are that Statin use may be beneficial for the primary prevention of CVD events in some adults with a 10-year CVD event risk of less than 10%, but the likelihood of benefit is smaller, because of a lower probability of disease and uncertainty in individual risk prediction. The attending clinicians may choose to offer a low- to moderate-dose statin to certain adults without a history of CVD when all of the following criteria are met: 1)If they are aged 40 to 75 years; 2) If they have 1 or more CVD risk factors (i.e Diabetes,dyslipidemia,hypertension, or smoking); and 3)If they have a calculated 10-year risk of a cardiovascular event of 7.5% to 10%.

General principles of Statin Use -

• Statins are the first choice in virtually all patients with elevated LDL-C.


• Start at the lower dosage of high-intensity statin in patients 75 years of age or older


• Secondary causes of hyperlipidaemia e.g. diabetes, hypothyroidism, liver/renal impairment should be excluded.


• Baseline lipids, liver and renal function, creatine phosphokinase (CK) ,TSH should be checked.

• Patient should be advised regarding medication e.g. adverse effects of statin treatment


• Statins should be taken in the evening for maximal effect, and require 4 weeks or more to exert their full effect on lipid concentrations


• LFT should be carried out before and within 4-6 weeks of starting statin therapy (1). Thereafter at intervals of 6 months to 1 year - earlier if clinical features of hepatotoxicity; also at the first review at 4-6 weeks - enquire about adverse effects such as itching, rash, myalgia, arthralgia, insomnia (1)
  
  
  
  • if satisfactory lipid control and no evidence of adverse effects then review again at 4-6 months, then 6-12 monthly
  
  
  • if unsatisfactory lipid control then measurements should be repeated 6 weeks after dosage adjustments are made until the desired lipid concentrations are achieved (2)
  
  
  • however NICE state that LFTs only need to be measured on three occasions:
    
    
    
    • baseline liver enzymes should be measured before starting a statin. Liver function (transaminases) should be measured within 3 months of starting treatment and at 12 months, but not again unless clinically indicated
    
    
    • people who have liver enzymes (transaminases) that are raised but are less than 3 times the upper limit of normal should not be routinely excluded from statin therapy
    
    
    
    
  
  
  
  


• treatment should be discontinued if serum transaminase concentrations rise to, and persist at, 3x normal range


• patients must be advised to report any unexpected muscle pain. Statins have been associated with the development of myositis, myopathy and myalgia. Some suggest if there is a marked elevation in creatine kinase concentration (>10 times the upper limit of normal) and a diagnosis of myopathy is suspected then the statin therapy should be stopped; however it has also been suggested that if the creatine kinase level is >5x the upper limit of normal then treatment should be stopped, while the patient is adequately monitored for muscular symptoms and cardiovascular risk (4).

• Give Rosuvastatin, atorvastatin when you want to lower LDL by more than 35%


• In CKD severe renal impairment give atorvastatin which does not require dose adjustment.


• In chronic liver disease suggest complete abstinence from alcohol and the use of pravastatin at a low dose (liver disease is unexplained aminotransferase values >3 times above upper normal range confirmed on repeat testing)


• Minimum pharmacokinetic drug interactions with atorvastatin ( not metabolized through the CYP3A4)


• Pravastatin and fluvastatin show least muscle toxicity Do a baseline CK levels as a reference


• Atorvastatin and rosuvastatin are more effective at lowering triglycerides (14 to 33 percent) than other statins in patients with hypercholesterolemia


• Atorvastatin at doses of 5, 20, or 80 mg/day produces reductions in triglycerides of 27, 32, and 46 percent, respectively, and in LDL cholesterol of 17, 33, and 41 percent, respectively


• In stable patients (outpatients) treat with high-intensity statin (atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg daily) and prefer the highest approved dose in most cases.


• In patients who do not tolerate one statin because of myopathy try another statin that may be better tolerated or to try alternative dosing regimens, often using low doses of rosuvastatin.


• For patients who cannot tolerate statin therapy consider a PCSK9 antibody.


• LDL-C should be monitored approximately six weeks after the initiation or change of treatment. If LDL reduction is substantially less than expected, possible non-tolerance or nonadherence to treatment should be carefully explored. Thereafter, measurement every 6 to 12 months is reasonable in patient’s adherent to lifestyle modifications to examine for continued adherence and increasing LDL levels with aging.


• With statins, lipid levels stabilize within several weeks after a change in dose, and so checking lipid levels six weeks after a dosage change should provide a reliable result.


• Statin therapy is contraindicated during pregnancy.


• creatine kinase should not be routinely monitored in asymptomatic people who are being treated with a statin - it was noted in the JBS2 guidance that a baseline CK measurement is common practice.


• if a person develops an unexplained peripheral neuropathy, statins should be discontinued and specialist advice sought

AACE and ESC/EAS guidelines have laid stress on lowering LDL-C but they consider patients with triglycerides >200 mg/dL to be at substantially increased ASCVD risk. Therefore they recommend that fibrates may be considered in patients with triglycerides >200 mg/dL and HDL-C <40 mg/dL mg/dL as this may improve CV outcomes.

Reference:

• (1) Prescriber 2000; 11 (23): 77-85.


• (2) Scottish Intercollegiate Guidelines Network (SIGN). Lipids and primary prevention of coronary heart disease. A National Clinical Guideline. www.sign.ac.uk [September 1999]


• (3) BNF 2.12


• (4) Current Problems in Pharmacovigilance 2002; 28: 8-9.


• (5) Drug and Therapeutics Bulletin 2001; 39 (3): 17-21


• (6) JBS2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 (Supp 5).


• (7) NICE (May 2008).Lipid modification - Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease