John Greenwood talks about the rationale behind the CE-MARC 2 trial and the efficacy and safety endpoints.
FILMED AT THE EUROPEAN SOCIETY OF CARDIOLOGY (ESC) ANNUAL MEETING, AUGUST 2016
WHAT IS THE RATIONALE BEHIND THE CE-MARC 2 TRIAL?
00:10 – At the current time we’re aware that invasive coronary angiography is often performed quite early in the diagnostic pathway for patients with suspected coronary heart disease. And from studies that have been published in the US, and other comparable studies in Europe, we can see that the rate of coronary angiography that don’t find any obstructive disease is around about 60%. So one could argue that a significant portion of those would be considered unnecessary. And so the CE-MARC 2 was a British Heart Foundation funded prospective multi-centre randomised control trial of three different diagnostic strategies in patients with suspected coronary heart disease to see whether we could reduce the rates of unnecessary coronary angiography in that patient group.
WHY ARE INVASIVE STRATEGIES SO COMMONLY EMPLOYED WHEN NON-INVASIVE STRATEGIES ARE AVAILABLE?
00:58 – Part of the reason comes around some of the pre-test likelihood models that have been used to estimate patients’ risk. So for example, when we look at the NICE 2010 guidelines that were produced in the UK, we can see that they broadly stratified the patients into three groups: low risk, who they suggested might benefit from anatomical imaging; intermediate risk for more functional imaging; and then high risk, anyone with a pre-test probability of over 60% would be potentially scheduled direct for coronary angiography. And it’s this labelling of patients’ high risk and stratifying them towards direct to a catheter-based investigation that seems to, or potentially produces a lot of unnecessary coronary angiography, and that was the purpose of the CE-MARC 2 trial.
WHAT STRATEGIES ARE BEING INVESTIGATED IN THE THREE STUDY ARMS?
01:50 – So we picked three different strategies: cardiovascular magnetic resonance imaging, as we believe this is one of the better functional imaging tests; myocardial perfusion scintigraphy which is the most commonly used functional test around the world. And we put those head to head against the UK NICE guidelines to see whether we could reduce the rates of unnecessary angiography in patients with suspected coronary heart disease.
WHAT ARE THE EFFICACY AND SAFETY ENDPOINTS OF THE TRIAL?
02:21 – So the primary endpoint, as I said, was the reduction of unnecessary coronary angiography as defined by an invasive FFR measurement, or QCA where that wasn’t physically possible. And we had some safety endpoints also built into the trial and those included the rates of detection of positive angiography and also the rates of major adverse cardiovascular events.
WHAT ARE THE MAIN FINDINGS OF THE TRIAL?
02:47 – The results of the trial were highly statistically significant. And we showed that a strategy involving cardiovascular magnetic resonance, significantly reduce the rates of unnecessary angiography compared to the UK NICE guidelines. And in fact those findings were comparable also for myocardial perfusion scintigraphy. Both the CMR and perfusion scintigraphy were the same at reducing those unnecessary angiography rates. And in terms of the secondary endpoints, there was no penalty for using functional imaging as a gatekeeper to the cath lab in terms of we didn’t find any higher rates of major adverse cardiovascular events.