engleski

Statins: benefits, limitations and risks of treatment

Increased cardiovascular (CV) risk is due to modifiable and non-modifiable risk factors. Among them, there is a robust scientific evidence that LDL-cholesterol (LDL-C) is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). Genetic studies and pharmacologically lowered LDL-C show a causality with reduced coronary heart disease. Reducing plasma LDL-C levels with a statin leads to dose-dependent reduction in the risk of major ASCVD events that is proportional to the absolute magnitude of the reduction in achieved LDL-C. A meta-analysis of data derived from 26 randomised controlled trials of statins including 170, 000 participants have shown that with every 1.0 mmol/L reduction in LDL-C, statins produce a relative risk reduction in major CV events of 22% at 1 year (standard statin dose vs. control). Although statins are drugs of choice for LDL-C lowering, reduction individually widely vary from 5% to 70%. Even more, not all statins are equally potent, atorvastatin and rosuvastatin being the most potent at highest recommended doses. A comparison of EUROASPIRE IV and V surveys over 5 years in coronary patients from 21 European countries has shown that high proportion of these very high risk patients didn’t achieve at that time recommended target LDL-C <1.8 mmol/L (82% and 71%, respectively). The important limitations of statin treatment are statin resistance and statin intolerance. Statin resistance is a failure to reach LDL-C target values despite best available therapy, and to prevent atherosclerotic changes and reduce cardiovascular outcomes. Possible causes of statin resistance are genetic factors, environmental influences, unrecognized secondary dyslipidaemia and pseudo-resistance due to physician-related or patient-related reasons (inadequate treatment, non-adherence or non-persistence). Pharmacogenetic testing before initiating statin therapy is still not recommended. Statin intolerance is inabillity of patient to tolerate statin therapy at all or to tolerate a full therapeutic dose because of adverse effects (muscle-related side effects, hepatic dyfunction, 10-12% increased risk of developing new-onset diabetes type 2, gastrointestinal and some other side effects). Risk factors for most common statin side-effects (myopathy, hepatic) should be recognised and if possible, treated or avoided. It is important to monitor for adverse reactions and adjust therapy according to 2019 ESC/EAS Guidelines for the management of dyslipidaemias. The Guidelines recommend target LDL-C values according to CVD risk levels: <3.0 mmol/L in low risk, <2.6 mmol/L in moderate risk, <1.8 mmol/L in high risk, and <1.4 mmol/L in very high risk individuals. When high potency statin at highest tolerable dose is not achieving target LDL-C in high or very high risk patients, ezetimibe and PCSK9 inhibitors should be added as a first and second step in combination therapy to reach the goal. These drugs are also alternative treatment in statin intolerant cases. Although statin treatment may be accompanied with some possible limitations and risks, there is highly favourable Benefit/Risk Ratio for statin therapy in CVD risk reduction. In primary prevention, statins are justified in high-risk individuals and always mandatory in secondary prevention.

statins ; clinical effects ; cardiovascular outcomes ; adverse effects

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