Why did the anti-C5 complement antibody pexelizumab not reduce infarct size but influence clinical outcomes positively when applied as adjunctive therapy to primary percutaneous coronary intervention?

Abstract

To the Editor: Mahaffey et al1 and Granger et al2 studied pexelizumab (Alexion Pharmaceuticals, Inc, Cheshire, Conn) as adjunctive therapy to fibrinolysis1 and to primary percutaneous coronary intervention (PCI)2 in acute myocardial infarction. Both groups obtained unexpected results: Mahaffey et al1 did not observe any positive action of pexelizumab, and Granger et al2 did not obtain any reduction of infarct size but did observe a substantial decrease in mortality. It has been proposed that: (1) thrombolytics themselves are quick and powerful activators of complement3; (2) thrombolysis transforms grossly visible anemic infarcts into hemorrhagic ones4; (3) alleged erythrocytes in hemorrhagic infarcts are, in reality, cardiomyocyte apoptotic bodies4; and (4) activated complement plays a decisive role in their formation.4 Using PCI instead of thrombolysis, Granger et al2 not only avoided a powerful activation of complement and a transformation of anemic infarcts into …