Kulkarni and Afshar-Kharghan administration of C1-INH between 6 and 24 hours after the onset of symptoms failed to decrease troponin I levels. There was no difference between patients who received C1-INH and those who did not with respect to the length of hospital or intensive care unit (ICU) stays, post-operative complications, or in-hospital mortality, regardless of the initiation time of C1-INH infusion. In another randomized, double-blind, placebo-controlled study, 80 patients with STEMI who underwent emergent CABG surgery were enrolled, with half receiving C1-INH and the other half receiving only a saline solution (Fattouch et al 2007). Patients received a bolus of C1-INH 10 min before reperfusion and then an intravenous infusion for 3 hours after surgery. Those receiving C1-INH showed a beneﬁt in the amount of inotrope drugs required, intubation time, length of ICU stay, and various measures of cardiac function, such as mean arterial pressure, cardiac index, and stroke volume. The levels of troponin I after reperfusion were signiﬁcantly lower in the C1-INH group as compared to the placebo group. However, the rate of early mortality was not signiﬁcantly different between the two groups. In one study of 564 patients, TP10 (a recombinant sCR1) or placebo was given to high-risk patients undergoing cardiac surgery requiring CPB (Lazar et al 2004). TP10 inhibited the complement system after 10–15 min of CPB, an inhibition which persisted until post-operative day (POD) 3. The primary endpoint in this study was death, MI, prolonged intra-aortic balloon pump support, and prolonged intubation. The TP10 group showed a lower primary endpoint event rate by 30% only in male patients. In a follow-up study of 297 female patients randomized to treatment with TP10 or placebo, it was shown that TP10 suppressed complement activation but did not reduce the incidence of death or MI by 28 days after surgery (Lazar et al 2007). A possible reason for this lack of difference is that the number of adverse events in the control arm of this trial was quite low to begin with, at 17%. Therefore, it became difﬁcult to prove any statistical differ- ence with only 297 patients. Thus, the study size combined with the low event rate in the placebo group together made it difﬁcult to show any beneﬁcial effect of TP10. Heparin, as mentioned earlier, has long been known to possess anticomplement activity. In a pig model of ischemia-reperfusion, 40 pigs were studied: 10 pigs received sCR1, 10 underwent surgery with heparin-bonded CPB (HB-CPB) circuits, 10 received sCR1 and underwent surgery with HB-CPB circuits, and 10 neither received sCR1 nor underwent surgery with HB-CPB circuits (Lazar et al 1999). As expected, sCR1 combined with the use of 680 HB-CPB circuits led to less myocardial tissue acidosis, better recovery of wall motion, less pulmonary edema, and smaller infarct size. In a human trial, the effect of heparin on complement activation was studied in 151 patients undergoing cardiac surgery. Heparin coating of CBP circuits reduced complement activation, especially C5b-9 formation, but did not reduce the release of the neutrophil granule enzymes myeloperoxidase and lactoferrin (Fosse et al 1997). Pexelizumab has also been studied in patients undergoing cardiac surgery requiring CPB. One of the ﬁrst studies conducted was a prospective, open-label, randomized phase I study in 17 patients who underwent primary, nonemergent CABG surgery with CPB. In the ﬁrst phase of the study, patients were randomized to receive escalating doses of h5G1.1-scFv (not yet known as pexelizumab) (Fitch et al 1999). In another part of the study, 18 patients were randomized into 3 groups and received placebo or one of two different doses of h5G1.1-scFv. It was shown that leukocyte activation, determined by expression of CD11b, was reduced in patients receiving the higher doses of h5G1.1-scFv. In those patients receiving the highest dose of h5G1.1-scFv (2 mg/kg), a 40% reduction in CK-MB was observed. In addition, in patients treated with the highest dose of h5G1.1-scFv, there was an 80% reduction in new cognitive deﬁcits as determined by sequential mini-mental status exams. In a follow-up to this study, a randomized, double-blind, placebo-controlled multicenter phase II trial in patients who underwent nonemergent CABG surgery with or without concomitant valve surgery, participants were randomized into three groups, those receiving placebo, those receiving a pexelizumab bolus, and those receiving a pexelizumab bolus and subsequent infusion (Shernan et al 2004). It was shown that giving pexelizumab as a bolus plus infusion reduced the composite of death or MI in patients undergoing CABG surgery only without valve surgery on POD 4 and POD 30. There was, however, no difference in the primary endpoint, namely the composite of death, new MI, left ventricular dysfunction, or new neurological events, between the two groups overall. This phase II trial was further analyzed from the neurological perspective in a follow-up substudy (Mathew et al 2004). Neurological and neurocognitive functions were assessed on POD 4 and POD 30 in patients enrolled in the substudy. Pexelizumab had no effect on overall cognition on either day. The only difference was in visuo-spatial function, which was signiﬁcantly better in the treated group as compared to the placebo group on POD 4 and POD 30. Biologics:Targets & Therapy 2008:2(4)