Dyslipidemia is one of the most important and common modifiable risk factors for cardiovascular disease (CVD). Lipid-lowering therapy is an integral part of intervention strategies in the prevention of CVD. Till this date, statins have remained the only hypolipidemics proven to reduce cardiovascular mortality and morbidity in patients with and without established CVD. This is why they have become the mainstay of therapeutic guidelines for the CVD management. (1, 2)

In recent years, guidelines for the management of dyslipidemia and on CVD prevention have placed greater emphasis on reaching target lipid levels and have introduced lower targets for patients at very high risk. In these patients, LDL cholesterol should be lowered to below 1.8 mmol/l or, if this target is unachievable, LDL cholesterol should be reduced at least by 50%. LDL cholesterol reduction by over 50% can be achieved with atorvastatin or rosuvastatin, the two most effective statins on the market. (1-3) New treatment targets in dyslipidemia were established based on the results from clinical studies, including two meta-analyses by the Cholesterol Treatment Trialists’ (CTT) Collaboration. Findings suggested that lowering of LDL cholesterol to lower therapeutic targets could produce additional benefits, without new or unexpected safety issues. (4, 5) The first meta-analysis has shown that every 1 mmol/l reduction in LDL cholesterol is associated with a corresponding 20-25% reduction in CVD mortality and non-fatal myocardial infarction. (4) The second cycle of analyses has shown that the reduction in major cardiovascular events is directly proportional to the absolute LDL reduction that is achieved, and that further benefit is gained from more intensive statin therapy even if LDL cholesterol is already lower than 2.0 mmol/l. (5) Moreover, other clinical studies have indicated that even a small reduction of LDL cholesterol has a significant clinical effect. Every 1% reduction in the LDL cholesterol level reduces the relative risk for major coronary heart disease (CHD) events by approximately 1%. Therefore, every 1% reduction counts and leads to a greater clinical benefit for the patient. (6) Rosuvastatin and atorvastatin, the two most potent statins on the market, which can produce a greater than 50% reduction in LDL cholesterol levels, could therefore halve the CHD risk over a 5-year period. (3, 6) The finding ‘the lower the LDL cholesterol concentration, the greater the risk reduction’ was also established in primary and secondary prevention of stroke. A meta-analysis of randomised trials of statins in combination with other preventive strategies has shown that each 1 mmol/l decrease in LDL cholesterol equates to a reduction in the relative risk for stroke of 21%. (7) (Table 1)

Parallel to clinical outcome trials, imaging studies have been conducted to examine the effects of statin therapy on the progression of atherosclerosis. The results of studies with high-dose atorvastatin or rosuvastatin therapy demonstrated a significant regression of coronary atherosclerosis. (8, 9)

Additionally, a study which compared the effect on percent atheroma volume (PAV) measured by intravascular ultrasound between the treatment with rosuvastatin 40 mg and atorvastatin 80 mg has found that the effects of these two treatments do not differ significantly. (9) The studies suggest that there is potential for a more optimistic strategy, in which aggressive lipid-modulating therapies could actually reverse the atherosclerotic disease process. (8, 9)

The evidence about the benefits of lowering LDL cholesterol to specific targets and of using sufficient doses to reach these targets is stronger than ever. However, many high-risk patients, particularly in secondary prevention, do not reach LDL cholesterol goals as defined in guidelines. According to the recently presented data from the EUROASPIRE IV study, a majority of coronary patients with dyslipidemia are taking lipid lowering drugs (almost exclusively statins) but are still inadequately treated. More than 40% of these patients do not reach LDL cholesterol levels <2.5 mmol/l. According to new guidelines, the target should be even lower, which results in even greater percentage of patients not reaching target lipid levels. (10) These patients are, despite treatment, at an increased risk for CV events.

The challenges for clinical practice remain to be confronted. Despite the well-established benefits and abundance of clinical management guidelines strongly advocating statin use in patients at higher CV risk, statins are usually prescribed at their lower doses and often not up-titrated to achieve lipid goals. Given the fact that the main purpose of reducing lipid levels is to gain the maximum clinical benefits, the guidelines address the need to initiate and then up-titrate drug therapies to achieve the treatment goals and improve eventfree survival. (1)

Krka has recognised this need and offers, as the first producer in the world, both potent statins in two additional doses, Atoris® (atorvastatin) 30 and 60 mg and Roswera® (rosuvastatin) 15 and 30 mg. Its broadest range of statin dosage options on the market allows adjusting the dose to every patient’s characteristics and needs. Many patients at an increased CV risk who are not reaching target lipid levels with currently available treatments, would have better chances of reaching them with atorvastatin 30 mg or rosuvastatin 15 mg. Atorvastatin 60 mg or rosuvastatin 30 mg can be particularly suitable as maintenance doses in patients in secondary prevention, e.g. after a CVD event, and in patients who need more intensive lipid management.

The efficacy and safety of Krka’s statins have been demonstrated in over 35,000 patients. A most recent non-interventional clinical study with Krka’s rosuvastatin, which also investigated additional strengths, confirmed the efficacy and safety of Krka’s rosuvastatin and its linear dose-response relationship. (11) Extensive clinical trials, together with vertically integrated production complying with the strictest European and international production and pharmaceutical standards, have played a crucial role in building trust in Krka’s medicines and have made Krka a leading producer of statins on the markets of Central, Eastern and South-Eastern Europe. Krka’s atorvastatin is the most prescribed statin on these markets. (12)

Having a complete range of doses can be one of the approaches to improve the success rate in reaching target lipidlevels in the management of hyperlipidemia. It might help improve clinical outcomes and provide maximum benefits of statin treatment for the patients. A better adherence to guidelines- based therapies could potentially reduce the public health and economic burden imposed by CVD.