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Numbers, Numbers, Numbers – So Many Details Hide in Plain Sight! Insights From HEAT-PPCI and HEAT-SEALED
In this issue of the Journal of Invasive Cardiology, Shahzad and colleagues1 describe the HEAT-SEALED trial, a programmatic component of the HEAT–PPCI trial, performed at one institution in the United Kingdom. The main trial1,2 demonstrated that in patients referred for primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), heparin was superior to bivalirudin with respect to the primary efficacy endpoint, assessed at 28 days, of all-cause mortality, stroke, reinfarction, or unplanned target-lesion revascularization (5.7% vs 8.7%, respectively; P=.01) without much difference between the two groups in the primary safety endpoint of major bleeding. This was a pragmatic study, enrolling almost all comers to one busy center in Liverpool, England. The authors noted that 1829 of a total of 1929 patients not participating in other clinical trials were enrolled and 1812 constituted the final analysis cohort. These very high enrollment figures represent a resounding success for a clinical trial design utilizing few exclusion criteria and a delayed written consent – features rarely used in the United States.
The same group of investigators are providing in this paper a detailed account of how enrollment proceeded and how patient dropout, from the early phase of STEMI notification until the procedure is completed, can be followed, understood, explained, and potentially prevented.
So what did we learn from HEAT-SEALED? By creating nine “denominators” or groups, the investigators identified the principal changes in number of patients considered for a specific activity or analysis. We learn, reassuringly, that in this system very rare instances of death occur before arrival to the hospital (1 case; 0.04%) and that ~1 in 6 activations of the STEMI network are unwarranted, similar to many other reports in Europe and the United States.2,3
We also learn that 78% of all activations were deemed suitable for emergency coronary angiography and possible revascularization. This denominator – n4 – is important because it provides the anchor for the HEAT-PPCI report, minus the patients already enrolled in other trials. Another nearly 10% of the original activations for STEMI did not have at coronary angiography the “smoking gun” necessary to trigger PCI, just as learned two decades ago in Primary Angioplasty in Myocardial Infarction (PAMI) 1.3,4 As we analyze the groups defined by n6 and n7, we are reassured that the incidence of severe coronary disease requiring emergency coronary artery bypass surgery is extremely low and should not affect our utilization of upfront antithrombotic therapy.
Undoubtedly, the most sobering group – n9 – teaches us that more than 40% of all patients for whom the cardiac catheterization team was emergently activated did not need it, or achieved suboptimal results. As the authors recognize, this is a far cry from the over 90% complete success rates quoted when using much more restricted analysis groups, although they can replicate this figure by dividing the number of patients in whom PCI was successful by those in whom it was attempted.
It may be important to focus on the persistently high rate of false-positive activations of the cardiac catheterization team, as it drains resources and reduces the enthusiasm for prompt response in the face of a high rate of “false alerts” – the so-called “STEMI fatigue.” Interestingly, there is much more “patient dropout” from lack of confirmation of STEMI by angiography than from incorrect diagnosis by paramedics or Emergency Department physicians. In the Ontario system, among 134 activations, 90% were deemed “clinical MI – n4” by the attending cardiologist, using the denominators promoted in this paper, but a full 21% did not have a culprit lesion supporting the diagnosis of STEMI – twice as much as the rate of disagreement between the various levels of patient evaluation.4,5 I doubt though that all systems are blessed with such a high level of diagnostic acuity. In our system (data not published), as many as two-thirds of the activations from the Emergency Medical Service (EMS) team are inaccurate. The presence of structural heart disease and congestive heart failure were the most common factors associated with the 36% rate of false activation of the STEMI network in an in-detail analysis from Boston.5,6
I applaud the authors for trying to standardize these important “denominators,” but I doubt that they can truly affect clinical practice. As they appropriately recognize, the accounting of the activity in this arena embraces many constituencies with different emphasis. Just like the United Kingdom, in the United States the focus of the National Cardiovascular Database Registry (NCDR), which tracks outcomes of PCI, is different from that of the NCDR-Acute Coronary Treatment and Intervention Outcomes Network (ACTION) registry tracking all MI hospitalizations in acute care hospitals, regardless of whether primary PCI was performed or not. Moreover, many of the groups defined by the HEAT-SEALED investigators are tracked by different entities, such as EMS, hospital administrators, interventional cardiology, etc, for different purposes.
As always, the devil is in the details. Let’s keep looking!
References
1. Shahzad A, Mars C, Dip HE, et al. Describing activity in primary percutaneous coronary intervention: an exploration of denominators. From the HEAT trial - a systematic evaluation of PPCI activations in Liverpool, explaining denominators (HEAT-SEALED). J Invasive Cardiol 2016;28:247-252. Epub 2016 Apr 15.
2. Shahzad A, Kemp I, Mars C, et al. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet. 2014;384:1849-1858.
3. Kontos MC, Kurz MC, Roberts CS, et al. An evaluation of the accuracy of emergency physician activation of the cardiac catheterization laboratory for patients with suspected ST-segment elevation myocardial infarction. Ann Emerg Med. 2010;55:423-430.
4. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med. 1993;328:673-679.
5. Cantor WJ, Hoogeveen P, Robert A, et al. Prehospital diagnosis and triage of ST-elevation myocardial infarction by paramedics without advanced care training. Am Heart J. 2012;164:201-206.
6. McCabe JM, Armstrong EJ, Kulkarni A, et al. Prevalence and factors associated with false-positive ST-segment elevation myocardial infarction diagnoses at primary percutaneous coronary intervention-capable centers: a report from the Activate-SF registry. Arch Intern Med. 2012;172:864-871.
From the New York Methodist Hospital, Brooklyn, New York.
Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Brener reports consulting and speaker fees from AstraZeneca and The Medicines Company.
Address for correspondence: Sorin J. Brener, MD, Professor of Medicine – Weill Cornell Medical College, New York Methodist Hospital, Brooklyn, NY. Email: sjb9005@nyp.org
