This editorial refers to ‘Optimal timing of coronary angiography and potential intervention in non-ST-elevation acute coronary syndromes’†, by D.G. Katritsis et al., on page 32
Imagine you have chest pain … A crushing discomfort that has begun at rest, irradiates to your left shoulder, and waxes and wanes over the course of several minutes. You cannot believe it is really an acute coronary syndrome (ACS), as you exercise regularly, are reasonably fit, and try to control your atherosclerotic risk factors as best you can! Still, you call 112 and rush to the Emergency Room for a quick triage. There, a non-ST-elevation ACS is indeed proposed as working diagnosis, but your colleagues face a difficult decision: ‘to cath or not to cath?’ And an even more difficult one, ‘when should we cath?’
As invasive cardiologists and coronary care unit specialists, we would not tolerate much delay. We would trust our own and our colleagues' invasive skills, and would surely prefer a quick rule in/rule out test such as coronary angiography, rather than a painful and passive wait-and-see approach. Yet, do we have evidence in support of such a rushed strategy?
Luckily, this issue provides a comprehensive and high-quality systematic review by Katritsis et al.1 comparing early invasive management against delayed invasive management in patients with non-ST-elevation ACS. As time is crucial in such a comparison, early means a median time from randomization (or admission) to coronary angiography ranging from 1.2 to 14 h, whereas late stands for 20.8–86 h delay in reaching the catheterization laboratory. Reading this work, given the overall good prognosis of patients with non-ST-elevation ACS enrolled in recent randomized trials, we were not expecting dramatic reductions in mortality, or huge changes in infarction rates. Indeed, the meta-analysis was not comparing percutaneous coronary intervention against conservative therapy or placebo, but just relatively subtle differences in the timing of a diagnostic procedure. Conversely, there remained the chance that earlier knowledge of coronary anatomy by means of invasive angiography could come at the price of an increased risk of adverse events.
Actually, early invasive management proved remarkably safe, with no significant difference in the risk of death, myocardial infarction, bleeding, or repeat percutaneous coronary intervention, in comparison with a delayed approach (all P > 0.05). Moreover, an early invasive strategy significantly reduced the recurrence of myocardial ischaemia [with a remarkable 0.59 risk ratio (95% confidence interval: 0.38–0.92), over a control event rate of 6.9%] and length of stay, which ranged from 55 to 120 h in the early invasive group compared with 77–168 h in the delayed invasive group [thus leading to a 28% reduction (95% confidence interval: 22%–35%)]. Despite the lack of data, such benefits are obviously capable of translating into significant cost savings as well.
Notably, as many as 24% of subjects managed with an early approach and 29% of those undergoing a delayed strategy were managed conservatively after diagnostic angiography, further strengthening the importance of early invasive management to rule out ACS. Indeed, confuting recent misperceptions about the role of diagnostic coronary angiography,3,4 refuting a diagnosis may be as important as confirming a diagnosis. For instance, appropriately excluding coronary atherosclerosis in a patient with non-ST-elevation ACS at high bleeding risk will enable therapeutic changes to minimize the likelihood of life-threatening haemorrhage.2 Conversely, recognizing early a left circumflex occlusion, which may often present as non-ST-elevation ACS despite ongoing transmural ischaemia, could have favourable remodelling and anti-arrhythmic effects, despite the benefits of percutaneous coronary intervention even later on.5,6
Thus, this new treatment paradigm can be incorporated into a comprehensive approach to patients with established or suspected ACS, including default coronary angiography for all patients with ST-elevation ACS and those subjects with non-ST-elevation ACS at high or moderate risk of ischaemic or bleeding events (Figure 1). Direct admission to the Coronary Care Unit or to the Medicine/Cardiology ward can be safely reserved for subjects with a low ischaemic risk or with any condition that may strongly contraindicate early angiography, such as history of anaphylaxis after contrast media administration, severe bleeding diathesis, or severe renal failure.
Bringing the patient to the cath lab is, however, only one of the necessary steps for effective management of ACS patients, as other similarly pivotal steps must be borne in mind. Radial or ulnar access should be used by all experienced operators to perform diagnostic angiography and, when appropriate, percutaneous revascularization, in order to minimize bleeding, increase patient comfort, and further reduce hospital stay and costs.7 If percutaneous coronary intervention is chosen, coronary stenting with second-generation drug-eluting stents and potent antithrombotic therapies such as intravenous glycoprotein IIb/IIIa inhibitors and prasugrel or ticagrelor, are mandatory in all those without contraindications.8–10 A similar aggressiveness should be pursued in both men and women, irrespective of ethnicity or socio-economic status, despite internal or external hurdles.11,12 Last but not least, even the laziest invasive cardiologists should be able to offer such early invasive management during weekends: if early is better than late during working days, such superiority is likely to increase for patients admitted on Friday evening, Saturday, or Sunday.
Yet, we already see the hands of ‘meta-sceptics’. Meta-analyses are facing a wave of criticism that resembles in many ways the early arguments (e.g. ‘mixing apples with oranges’), but also includes the issue of duplication.13,14 Accordingly, opponents of evidence-based medicine will caution against applying such ‘average’ findings to any individual patient. Nonetheless, even the fiercest enemies of systematic reviews will have to acknowledge the outstanding safety and promising role of early invasive management of ACS. For instance, major bleeding occurred with lower frequency with this strategy in all the four trials [4.0% vs. 6.8% in Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention (ABOARD), 7.3% vs. 12.6% in Early or Late Intervention in Unstable Angina (ELISA), 3.0% vs. 3.9% in Intracoronary Stenting With Antithrombotic Regimen Cooling-Off (ISAR-COOL), and 3.1% vs. 3.5% in Timing of Intervention in Acute Coronary Syndromes (TIMACS)].1 Even using a rule of thumb approach, this means a 50%*50%*50%*50% = 50%4 probability, thus 6.3%.
Acknowledging the dominant present role of early invasive management encompassing coronary angiography across the whole spectrum of ACS patients, what does the future hold for cardiologists managing this condition? The truth is that in 5 or 10 years time catheter-based angiography will no longer be so crucial. With the ever-expanding role of computed tomography (CT) for triple rule-outs,15 default invasive angiography will likely be reserved for very high-risk patients only, with CT and, possibly, magnetic resonance imaging, playing a more prominent role for all other patients, especially in centres without 24/7 access to the cath lab.
In conclusion, early invasive management of patients with non-ST-elevation ACS is safe and reduces recurrent ischaemia and length of stay. Thus, attempts should be made to shorten time to the cath lab for most if not all such subjects.
Conflicts of interest: G.B.-Z. has the following conflicts of interest: Abbott, Cordis, Medtronic (consulting fees); AstraZeneca, Bristol Myers Squibb, Chiesi, Medtronic, sanofi aventis, The Medicine Company (lecture fees). A.A. has received research grants and speaker honoraria from Gilead Sciences.