Authors

• Diana Rudan — Klinička bolnica Dubrava, Zagreb, Hrvatska — ORCID: 0000-0001-9473-2517

Abstract

Cardiovascular diseases are the leading cause of death in the world with hyperlipidemia being one of the most important risk factors in their development. Therefore, numerous randomized controlled trials conducted, showed decrease morbidity and mortality from adverse cardiovascular events by effective lipid reduction. Statins are the most effective medications used in treatment of hyperlipidemia. Rosuvastatin represents a “new generation” statin. It is a synthetic statin that inhibits the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, and therefore reducing the synthesis of endogenous cholesterol. The major effect of rosuvastatin is the reduction of LDL-cholesterol, and total cholesterol in the blood. It is the only statin that has been shown to increase the levels of HDL-cholesterol up to 15%. The anti-inflammatory, anti-oxidative, and anti-thrombotic effects of the drug were demonstrated in various studies, causing further decrease in cardiovascular morbidity and mortality, that effect is beyond the one described only by the reduction in total cholesterol levels. The most common side-effect of statin treatment is myalgia, causing the non-adherence and discontinuation of the medication, leading to “alternative” drug treatment. However, the approach of alternative drug treatment often showed itself to be ineffective solution. Since treating hyperlipidemia is crucial in reducing cardiovascular risk, the importance of adherence to treatment, and achieving patient compliance to statin therapy must be emphasized. Rosuvastatin is available in 6 different doses from 5 to 40 mg, allowing the physician to adjust the dose of medication according to the patient’s needs, to maintain highest treatment effect while reducing unwanted side-effects at the minimum.

Keywords

Ključne riječi: rosuvastatin, prevencija, kardiovaskularne bolesti, rosuvastatin, prevention, cardiovascular diseases

DOI

Full Text

Rosuvastatin as a “super” statin in primary and secondary prevention of cardiovascular events Cardiovascular diseases (CVD) are the leading cause of death in the world: resulting in 42% of total mortality in women, and 38% in men before the age of 75, in Europe, caused by cardiovascular diseases. Therefore, to prevent development of CVD it is highly important to identify, and modify cardiovascular risk factors. The studies showed a 50% reduction in mortality from coronary heart disease by changes in behavior affecting the CVD risk factors, and a 40% reduction due to improved treatment of CVD risk factors. There are many myths associated with statin treatment, including the claims: that no-one treated elevated cholesterol before and people lived longer, that there is no point treating persons over the age of 60, as the statin therapy would not extend the lives of patients at that age, that there is no benefit to take statins during lifetime, that they could damage the liver and muscles, and finally that statins could be the cause of diabetes. However, tens of thousands of patients in clinical trials and hundreds of millions of patients receiving statin therapy all over the world, showed that statins are the most effective drugs in reducing cardiovascular morbidity and mortality. Additionally, as the most cardiovascular events happen in the patients older then 60, taking into account estimation that by the 2020, the average lifespan of women will be above 80 years, and in men above 75 years, the importance of statins in primary and secondary prevention of CVD becomes even clearer (1-5). Although different types of statins are currently available on the market, due to their effectiveness and safety, atorvastatin and rosuvastatin are the ones most commonly prescribed. Rosuvastatin is a synthetic hydrophilic statin that works by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (3-HMG-CoA). It reduces LDL-cholesterol (LDL) and total cholesterol values, while being the only statin that also increases HDL-cholesterol (HDL). Its elimination half-life is 19 hours, and it is taken orally once a day irrespective of food intake. Two third of rosuvastatin is excreted dominantly unchanged via the kidneys, while the rest of the drug is excreted through biliary system (using the transport proteins OATP1B1 and BCRP). Therefore, care must be taken in patients with moderately impaired renal function, and the maximum daily dose of rosuvastatin in kidney impairment must be limited to 20 mg. Only 10% of rosuvastatin is metabolized through the liver, making it an appropriate choice of treatment for patients on multiple medications. It has been demonstrated that rosuvastatin has a low potential for interaction with ACE inhibitors, sartans, beta-blockers, oral antidiabetics, nonsteroidal antirheumatics, and antibiotics, which are the drugs most commonly prescribed in older patients, and patients with CVD. It should be noted that medications that use the transport proteins OATP1B1 and BCRP in the liver (such as cyclosporine and certain antiviral drugs) can influence the concentration of rosuvastatin in the blood, in which circumstances alternative treatment should be considered. Severe renal impairment, pregnancy, and breastfeeding are the only absolute contraindications for Rosuvastatin treatment. Myopathy is one of the most common side-effect during statin treatment, therefore, rosuvastatin should be avoided or used cautiously in patients with known predisposition to myopathy (5). Rosuvastatin is shown to be the most effective statin on the market in reducing LDL values in blood, that also effectively increases HDL, therefore the beneficial effect on atherogenic index of plasma (log(TG/HDL)) of all statins is the strongest with the use of rosuvastatin. Given that it bypasses the liver enzyme metabolism, the likelihood of side-effects is lower than with the use of lipophilic statins such as atorvastatin. This is highly important in older patients that are on treatment with multiple medications. Finally, diabetics are a subgroup of patients in which rosuvastatin is shown to be more effective in comparison to other statins (6). Rosuvastatin is also showing additional pleotropic effects, further reducing cardiovascular risk regardless of the decrease in cholesterol levels. These effects are primarily attributed to its anti-inflammatory effects, improved endothelial function, and the stabilization of atherosclerotic plaque, which leads to plaque regression, and slowing the progression of atherosclerosis (3). Due to this effect, rosuvastatin has been shown effectiveness in the prevention of major cardiovascular events in women above the age of 60 and men above 50 with normal LDL values, and high values of inflammatory markers (hs-CRP) (7). Rosuvastatin is present at the market as tablets in 6 different doses: 5, 10, 15, 20, 30, and 40 mg, which allows dose titration to achieve appropriate reduction in LDL values according to the guidelines of the European Society of Cardiology, and European Atherosclerosis Society. The wide range of rosuvastatin dosage allows the physician to tailor the treatment to the needs of the individual patient, increasing the likelihood of achieving targeted lipid values (8). However, data from clinical practice show that the majority of the physicians do not usually prescribe the highest doses of statins. Physicians are generally reluctant to double the existing dose of statins, with most patients receiving one of the two lowest doses. Now days, rosuvastatin is the most frequently used statin treatment, especially in diabetics due to its potency on lowering LDL cholesterol, but also regarding the overall beneficial effect on the lipid profile. Rosuvastatin is chosen in treatment of patients with especially high lipid values, in patients with very high cardiovascular risk, and patients where other statins failed in achieving targeted lipid levels. ## Conclusion Rosuvastatin is an hypolipemic drug, with numerous effects that cause significant reduction of total and LDL-cholesterol, and increase in HDL, used to achieve the targeted lipid profile. It is effective in primary and secondary prevention of cardiovascular events, especially in diabetics, and its effectiveness has been shown when treatment failure with other statins is present. Based on the current state of knowledge, statins have been a well-tested therapy of choice for more than 25 years. They not only effectively reduce the level of lipids in the blood, but also have many other beneficial effects, thus reducing cardiovascular risk and extending the patient’s lifespan (8). Statins are also a safe choice of therapy, since they have very few side-effects. Therefore when indicated, and should be taken lifelong. Unfortunately, due to inadequate education of both physicians and patients, and the lack in their communication, with consequent failure in adherence to the treatment, statin therapy is often discontinued, and even when taken regularly, it is often underdosed. However, continued physicians and patients education on the effectiveness, safety, and necessity of taking statins on the one side, and the possibility of titrating rosuvastatin on the other, will allow achieving targeted lipid values, and consequently enable the highest benefit from statin treatment.

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