Disbalance between mortality and non-fatal vascular events in the CHAMPION-PHOENIX trial: The cangrelor efficacy challenge

SummaryThe recently published, largest trial with cangrelor, the Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION)-PHOENIX, suggested that the experimental agent significantly reduced the rate of stent thrombosis (ST) and myocardial infarction (MI) during PCI at 48 hours (h) and 30 days. However, the declared impressive cangrelor vascular non-fatal benefit was contradicted by identical deaths at 48 h, and a trend toward excess mortality at 30 days. We analysed the mismatch between outcomes in the CHAMPION-PHOENIX trial. The trial reported identical mortality (18 death in each arm; odds ratio [OR] 1.00 (0.52–1.92); p>0.999) at 48 h, but more deaths, 60 vs 55, after cangrelor at 30 days. There was a significant reduction of ST from 0.8% (n=46) of the patients in the cangrelor group versus 1.4% (n=74) in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; p= 0.01) at 48 h, and a persistent but less impressive ST prevention benefit OR of 0.68 (0.50=0.92, p = 0.01) at 30 days. There were also 48 less MI’s following cangrelor usage enforced by a significant difference (odds ratio 0.80 (0.67–0.97) p = 0.02), which was also less prevalent at 30 days (OR 0.82 (0.68–0.98), p = 0.03). The reported ST/MI advantage should result in at least a trend towards numerically less deaths after cangrelor at 30 days follow-up, which was opposite of the results reported in CHAMPION- PHOENIX trial. Efficacy of cangrelor is challenged by the disproportional “reduction” of ST and MI conflicting with identical mortality at 48 h and worsened at day 30 fatalities. The dissociation between vascular mortality and non-fatal vascular ischaemic occlusions, unless compensated by some other unreported cause(s) of death, should be explored and explained. Unadjudicated 30-day outcomes, and all ST types should be fully disclosed. The ongoing FDA cangrelor review should focus on appropriate event count and/or possible mismatch between site-reported and extra adjudicated events in the CHAMPION-PHOENIX trial.

Carotid Endarterectomy: Are We Meeting the Two Week Target?

Objective It has been recommended that carotid endarterectomy should be carried out within fourteen days of the index event if maximum stroke prevention benefit is to be achieved. The aim of this study was to see whether this target was being met in our region and where in the pathway delays occurred. Methods This was a retrospective review of all patients (n=75) undergoing carotid endarterectomy in 2006 in a regional vascular unit. Eleven patients were excluded as the timing of onset of symptoms was unclear, leaving 64 patients for further analysis. Results The median time-interval from onset of symptoms to surgery was 47 days (interquartile range 32-65 days). Five of 64 patients (4.5%) had a carotid endarterectomy within 14 days. Median time from onset of symptoms to presentation to health services was one day (IQR 0-7 days), from presentation to health services to neurovascular clinic was 16 days (IQR 10-23 days), from neurovascular clinic to vascular surgery clinic was 13 days (IQR 9-24 days), and from vascular surgery clinic to operation was 13 days (IQR 8-22 days). Fifteen of the 51 patients (29%) attending a neurovascular clinic and five of the 57 patients (9%) attending a vascular surgery clinic were seen within 14 days. Conclusion The fourteen-day target is difficult to achieve due to the number of steps in the referral pathway. This delay may be jeopardising outcome. Reduction in the delay to surgery would require a multi-disciplinary approach and should involve education of the general public.