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The Effects of the Direct Lipoprotein -associated Phospholipase A2 Inhibitor Darapladib on Human Coronary Athlerosclerotic Plaque.

Hot Line Update III

Presenter: Wijns William (Belgium)

The discussion from Prof. Wijns is available.

Discussant report:

Crea Filippo (Italy


The first strength of this study is that it is extremely innovative. Indeed, it targets Lp-PLA2, an important inflammatory mediator found in atherosclerotic plaques. The notion that Lp-PLA2 might be in the causal pathway leading to acute vascular events is supported not only by experimental and post-mortem observations, but also by the lower incidence of cardiovascular events consistently observed in carriers of missense mutations of the gene encoding for Lp-PLA2. A second strength of the study is its robust design, including core lab analysis of both imaging and biomarkers. A third strength is the large experience of the investigators.

This study presents, however, some limitations. The most important is the utilization of non-validated surrogate end-points such as VH and palpography, rather than that of validated surrogate end-points such as carotid IMT, FMD or coronary plaque volume, known to be correlated with clinical end-points. A second limitation of the study is lack of internal coherence of findings obtained using different imaging techniques. Indeed, it is not clear why the reduction of the necrotic core at VH observed in patients randomized to darapladib did not translate into an improvement of plaque deformability at palpography, thus casting some shadows on the biological value of these parameters.


In conclusion, IBIS-2 is an innovative trial targeting inflammation through inhibition of Lp-PLA2, which might be in the causal pathway leading to acute vascular syndromes. Darapladib failed, however, to significantly affect the two primary end-points of the trial (plaque deformability at palpography and hs-CRP levels). Thus, further studies using validated surrogate end-points are appropriate before considering large trials with clinical end-points.




Hot Line Update III

Notes to editor

This congress report accompanies a presentation given at the ESC Congress 2008. Written by the author himself/herself, this report does not necessarily reflect the opinion of the European Society of Cardiology.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.