Two negative studies weren’t enough to stop the Medicines Company from CHAMPION PHOENIX, the third attempt at demonstrating cangrelor is useful during PCI.
Cangrelor is a direct-acting platelet adenosine diphosphate inhibitor – same as prasugrel and clopidogrel – that differs in its half-life and route of administration. Rather than clopidogrel, which is a long-acting oral loading dose during STEMI, cangrelor is a continuous intravenous inhibitor that wears off after minutes. This has some theoretical advantages, such as when multiple lesions are found on invasive angiography and coronary bypass need not be delayed for the antiplatelet effects of clopidogrel to wear off.
So, PHOENIX follows up CHAMPION PCI and CHAMPION PLATFORM, each of which were negative for their primary combined endpoint of death, myocardial infarction, or ischemia-driven revascularization. In fact, these studies were stopped at their interim analysis for futility, as they were unlikely to show superiority given the planned enrollment.
So, why does PHOENIX succeed where others have failed? Well, they changed the primary endpoint to a new composite – death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis. And, PHOENIX shows a 0.8% vs 1.4% advantage to cangrelor for stent thrombosis – which accounts for most of the new advantage in primary outcome. In previous CHAMPION studies, stent thrombosis was 0.2% vs. 0.3% and 0.2% vs. 0.6%. So, truly, cangrelor succeeds here mostly because the clopidogrel group fares so much more poorly, rather than on its own merits. Considering 25.7% of the clopidogrel group received only 300mg rather than 600mg, and 36.6% received their clopidogrel during or after PCI, it’s no wonder they had greater stent thrombosis in this study.
It’s pretty clear the Medicines Company learned from its two negative studies and rigged the third one to succeed – and kept it just underpowered enough that severe or moderate bleeding with cangrelor didn’t reach statistical significance (0.6% vs. 0.3% p = 0.09). This reinforces a bias frequently seen in sponsored trials – failure at first begets further trials, while initial success doesn’t lead to confirmatory RCTs that might cast doubts upon the authenticity of the golden goose.
“Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events”
www.ncbi.nlm.nih.gov/pubmed/23473369