Fourier Study: Has it brought little or a lot of good? Or has it just failed to reach exaggerated expectations?
Abstract
The drugs of a novel class of hypolipidemic agents, PCSK9-inhibitors, are now approved for clinical use. In many EU countries, including Slovakia, these drugs are also available in clinical practice.
Since this "biological therapy" is admittedly costly, their administration is subject to restrictions that vary by country. Of the two molecules of PCSK9-inhibitors (evolocumab and alirocumab), we shall first focus on evolocumab and then in particular on the Fourier study.
The Fourier study was presented at the congress of the American College of Cardiology in March 2017 It is truly a "mega-study" which involved more than 27 500 patients with a proven cardiovascular disease, who had been treated with statins and in spite of a maximum tolerated hypolipidemic therapy they had had LDL-C over 1.8 mmol/l or non-HDL-C over 2.6 mmol/l. They also had another significant cardiovascular risk factor.
Further on they received a maximum statin (+ ezetimib) hypolipidemic therapy in combination with evolocumab or placebo. The results of the study were clearly positive.
The primary target indicator decreased by 15%, the secondary (cardiovascular death, myocardial infarction and stroke) was reduced by 20%. Both the results were statistically significant.
A marked decrease in LDL-C by almost 60% was recorded. The treatment was well tolerated and practically without adverse effects.
Despite very favourable results we quite frequently see discussions to consider whether the achieved results are sufficient, or rather sufficiently convincing. This paper answers these questions clearly: YES.
The therapy with evolocumab led to statistically and clinically significant reduction of cardiovascular events. The fact that the results equivalent to the historical studies with statins (e.g. "4S") have not been reached is not difficult to explain.
It also needs to be admitted that some of us, probably under the influence of really extraordinary effects of PCSK9-inhibitors, expected a miracle rather than a very positive outcome.