Abstract
Cardiovascular diseases (CVDs) still remain a crucial problem for all western countries as well as for those countries that follow their pattern of economic development. Even though the treatment of CVDs has gone through enormous success in recent years, risk factor control is of no less (or even more) importance.
Among risk factors, LDL-C plays an essential role as a primary goal of treatment. Nonpharmacological measures with an emphasis on lifestyle modification are the mainstay of treatment.
In a high proportion of patients, however, pharmacological treatment must be used. Statin therapy is a cornerstone in treatment, with ezetimib being added in combination therapy to reduce LDL-C.
PCSK9 inhibitors represent a new class of drugs that, in a dramatic way, positively affect the lipid profile (particularly LDL-C, but also apo B and Lp/a/). These lipid effects have been very closely studied in a number of trials in the past few years.
Further studies then investigated the safety profile. All these studies have brought positive results only.
Moreover, in the last year, large trials (megatrials of tens of thousands of patients) have been published that studied the effects of treatment with PCSK9 inhibitors on CV morbidity and mortality. These trials, the FOURIER and ODDYSEY outcomes, then showed not only a reduction in CV risk and CV episodes, but also a reduction in overall mortality.
The present paper deals mainly with the experience and outcomes that have been obtained with evolocumab, available under the brand name Repatha. The outcomes of trials are discussed, with a particular focus on the FOURIER trial and the safety analyses that addressed, among other things, neurocognitive functions (the Ebbinghaus trial) or the development of new diabetes mellitus (DM) that, unlike with statins, was not observed.
Attention is also paid to selected subgroups of patients treated with PCSK9 inhibitors (with a positive effect mostly), e.g. patients with familial hypercholesterolaemia (FH) or those with DM.