The role of ezetimibe in LDL cholesterol goal attainment in very high risk patients: the rosuvastatin monotherapy looks to be insufficient

Key words::

• LDL
• cholesterol
• prevention
• statin
• ezetimibe

One of the most important components of cardiovascular prevention is the achievement of appropriate LDL cholesterol level. In this process the drugs of first choice are the statins, their favorable effect on cardiovascular events and total mortality was proved by a series of studies. This has been affirmed by the Cholesterol Treatment Trialists’ Collaboration (CTTC) meta-analysis involving data of nearly 130,000 patients, where the decrease in major vascular events per 1.0 mmol/L LDL cholesterol reduction was 21%, that of all-cause mortality 10%1.

At the same time in everyday lipid lowering practice it is well known that in a considerable number of cases statin monotherapy is not sufficient to achieve goals. In LDL cholesterol reduction the administration of ezetimibe proved to be an outstanding help. Its damaged prestige was restored by the result of SHARP (Study of Heart and Renal Protection) study showing that the use of a combination of ezetimibe and simvastatin 20 mg significantly reduced the occurrence of cardiovascular events (e.g. 17% decrease in the rate of major atherosclerotic events, p = 0.0022)2.

A recent meta-analysis of CMRO (Mikhailidis et al.3) assesses the beneficial effects of ezetimibe treatment based on the data from 13 studies and 5080 patients. The main message of this publication with its slightly complicated and for general clinicians hard-to-understand statistics was that the odds ratio to attain LDL-C treatment goal is 2.45 (1.95, 3.08), (p = 0.007) for adding ezetimibe to statin therapy vs. doubling the statin dose.

The inefficiency of statin monotherapy (even in the case of the most potent rosuvastatin) and the usefulness of administering ezetimibe would be supported by the Hungarian CORVUS (COntrolled TaRgets for High Vascular Risk Patients Using Effective Statins) study conducted among specialists where the effect of switching to high-efficient rosuvastatin on the success of lipid lowering therapy in 1385 high risk patients was investigated. In this 3-month, multicenter, prospective, observational, non-interventional open-label study 1077 out of 1385 patients belonged to the very high risk category. During the 3-month treatment period in the whole patient population the level of total cholesterol decreased by 25.2%, LDL cholesterol by 35.0% and triglycerides by 21.0%, and HDL cholesterol level increased by 5.1%. At the end of the study the rate of achieving the 100 mg/dl LDL cholesterol target level was 58%, that of HDL cholesterol target level (40 mg/dl in males, 50 mg/dl in females) was 67% and in the case of triglyceride levels (150 mg/dl) 48%. The 58% in 100 mg/dl LDL cholesterol achievement rate is a very good result compared to that found in another observational study carried out in Hungary between 2004 and 2008, where among specialists the best result was 43%4. The 58% LDL cholesterol goal attainment in CORVUS is comparable to the results of the CEPHEUS study in which it varied between 40% and 68% in different European countries5. But in the 1077 very high risk patients in the CORVUS study the 70 mg/dl LDL cholesterol achievement rate proved to be only 19%.

Based on these results we can state that the administration of statin monotherapy, even the highly efficient rosuvastatin, in a large number of cases is not enough to achieve target values, mainly in very high risk patients. The use of ezetimibe can provide a great help when striving for higher goal attainment, i.e. higher quality of treatment. It would be more expedient to include in the guidelines that in very high risk patients with high LDL cholesterol level the treatment after a moderate or high dose of statin, if it proved insufficient, should be rapidly changed to combination therapy.

Transparency

Declaration of funding

The authors declare no conflict of interest and have received no payment in preparation of this manuscript.

Declaration of financial/other relationships

The authors have previously received sponsorship from AstraZeneca, Hungary.