Mechanisms were PKG-dependent given that both pharmacological and genetic knockdown of PKG abrogate the effects,46 while downstream signalling pathways are more contentious, involving mitochondrial function (briefly summarised in figure 5).11 Comparative clinical data are lacking, but sildenafil appears to lengthen ischaemia/angina threshold relative to placebo,47 and PDE5i users have lower mortality post-MI.6 7. This evidence concerns the gene PRKG1 and angina pectoris.