Vascular Events After ACS: Lipoprotein(a) and Alirocumab

In this study by Schwartz and colleagues, data from the ODYSSEY OUTCOMES trial were used to test whether the PCSK9 inhibitor alirocumab could reduce peripheral artery disease (PAD) events and venous thromboembolism (VTE), as well as investigate the potential mechanisms for such reductions. In regard to PAD events (defined as critical limb ischemia, limb revascularization, or amputation for ischemia), there was a 31% relative risk reduction with alirocumab, an effect that was even more pronounced in patients with a known history of PAD. Interestingly, this reduction in PAD events was associated with degree of Lp(a) lowering, rather than reductions in LDL-C, suggesting that Lp(a) may be an important mediator in the development of PAD and a potential target for therapy. Although there were fewer VTE events in this study, a similar signal was observed. There was a trend toward reduction in VTE with alirocumab and the degree of Lp(a) lowering was again associated with this effect.

These reductions in PAD and VTE events are consistent with findings from evolocumab in the FOURIER trial, suggesting a class effect for PCSK9 inhibitors. As the use of PCSK9 inhibitors for the reduction of cardiac events increases, we now know our patients may also derive important vascular benefits that reduce the overall burden of PAD and VTE. However, if Lp(a) lowering is in fact the mechanism for these vascular benefits, then Lp(a)-specific therapies may prove to be more effective than PCSK9 inhibitors. As both RNA interference and antisense oligonucleotide therapies against Lp(a) progress to phase III clinical trials, their effect on PAD events and VTE will be of great interest. These clinical trials have the opportunity to confirm the Lp(a) hypothesis and identify more potent therapies for preventing PAD and VTE events.