Speedy Angiography Needed in NSTE ACS Without Prior P2Y12 Inhibitor

Marlene Busko

November 14, 2018

CHICAGO — Patients with non-ST-segment-elevation acute coronary syndrome (NSTE ACS) who do not receive a P2Y12 antagonist such as clopidogrel, ticagrelor, or prasugrel before coronary angiography need to undergo this procedure promptly, new research suggests.

The randomized EARLY trial showed that among NSTE ACS patients who were not administered a P2Y12 agonist prior to being sent to the catheterization laboratory, those who received early revascularization (within 2 hours) were much less likely to experience recurrent ischemia within 30 days than those for whom revascularization was delayed (12 to 72 hours later).

Laurent Bonello, MD, PhD, from Aix-Marseille University in France, reported the results here at the American Heart Association (AHA) Scientific Sessions 2018.

The findings build on previous work, including the A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial (ACCOAST) trial, which showed that among patients with NSTE ACS who were scheduled to undergo catheterization, pretreatment with prasugrel did not lower the rate of major ischemic events within 30 days but did increase the rate of major bleeding complications.

The current study, Bonello told theheart.org | Medscape Cardiology, shows that "if you're not pretreating your patient" with a P2Y12 inhibitor, you should send the patient to the cath lab quickly "and not wait for several hours."

On the other hand, "if you want to delay an invasive strategy, then you probably have to stick to pretreatment" with a P2Y12 inhibitor, as recommended in the guidelines.

"Otherwise, you're going to very often activate the cath lab at night, during Sundays" and other off hours, he said.

Others noted some trial limitations but agreed with this conclusion. The invited discussant, Gilles Montalescot, MD, from the Institut de Cardiologie, Pitié-Salpêtrière, in Paris, France, who had led the ACCOAST trial, noted that by using "a strategy of loading P2Y12 antagonists after seeing the coronary angiogram, EARLY has extended the ACCOAST data to P2Y12 antagonists other than prasugrel," which in his view is an important finding.

EARLY also showed that "if the waiting period for a coronary angiography exceeds 48 hours or when a conservative strategy is decided, the administration of a P2Y12 antagonist needs to be considered," he said.

Similarly, session moderator and American College of Cardiology (ACC) President C. Michael Valentine, MD, when invited to comment, told theheart.org | Medscape Cardiology that the take-home message is that it is safe to move quickly to the cath lab with patients with non-ST-segment-elevation MI, "but if you're not going to move quickly, you need to ensure that patients get guideline-based optimum medical therapy in advance."

Early Angiography Better?

Guidelines say that high-risk patients with NSTE ACS should undergo percutaneous coronary intervention (PCI) within 2 hours and tthat intermediate- to high-risk patients should undergo revascularization within 24 to 72 hours, said Bonello.

However, he noted that since the publication of ACCOAST, "a significant proportion of patients with NSTE ACS are not pretreated anymore before their scheduled coronary angiography."

However, the optimal timing for coronary angiography in patients who are not pretreated with a P2Y12 antagonist is unknown.

To investigate this, the researchers randomly assigned 741 patients who were scheduled for coronary angiography at 13 centers in France with 24/7 cath labs either to undergo early vascularization or late revascularization with no pretreatment.

The primary outcome was the combined endpoint of recurrent ischemic events &mdash defined as ischemia symptoms (chest pain), ventricular arrhythmias, acute pulmonary edema, or cardiogenic shock requiring urgent revascularization &mdash or cardiovascular death within 30 days.

For both groups of patients, the mean age was 65 years, 70% were men, and 30% had diabetes.

About 21% were taking aspirin, and 20% were receiving a P2Y12 inhibitor &mdash clopidogrel (15%), ticagrelor (5%), or prasugrel (1%).

The patients' mean GRACE risk score was 122; a score of 109 – 140 indicates intermediate risk of in-hospital mortality, and a score >140 indicates a high risk.

The delay from randomization to coronary angiography was a median of <1 hour in the early revascularization group and 18 hours in the delayed revascularization group.

Three quarters of the patients underwent PCI; 22% received medical therapy only; and 3% underwent coronary artery bypass grafting.

At 30 days, the combined endpoint of cardiovascular death or a recurrent ischemic event occurred in 21.3% in the delayed vs 4.4% in the early coronary angiography group (hazard ratio, 0.17, 95% confidence interval, 0.10 – 0.30, P < .001).

Closer analysis revealed that there was no significant difference in the rate of cardiovascular death in the two groups: four patients (1.1%) vs two patients (0.6%; P = .69).

However, recurrent ischemic events occurred in 75 patients (21%) in the delayed coronary angiography group vs 14 patients (4%) in the early coronary angiography group (P < .001).

The recurrent ischemic events were almost all ischemia symptoms. Only two or fewer patients had ventricular arrhythmia, pulmonary edema, or cardiogenic shock.

The early coronary angiography strategy was significantly better than the delayed strategy in all prespecified subgroups except for women and patients who did not receive PCI, possibly owing to the fact that there were fewer patients in those subgroups.

"Good News, but Also a Warning"

According to Montalescot, on the basis of GRACE score, this was more of a low- to intermediate-risk patient population.

Moreover, 20% of patients were taking a P2Y12 antagonist when they were admitted, and the soft endpoint of recurrent ischemia is subject to interpretation bias.

Nevertheless, he said, the findings are consistent with previous studies that found that early coronary angiography was associated with a reduced risk for recurrent ischemia.

A "lingering question," said Valentine, "would be, had they used P2Y12 inhibitor–loading" in the 12- to 72-hour group, would that group have had poor outcomes, or would those patients have stabilized? "If so, then you wouldn't have to go in within 2 hours."

On the other hand, he said, another positive finding in the trial is that patients who went to the cath lab within 2 hours did very well. "So that's encouraging for centers who are taking patients to the lab quickly," he said. There seemed to be no time that was "too quick."

"I think there is good news in that trial, but there is also a warning," he summarized. "If there is a delay, guideline-based medical therapy should be aggressive."

The study was funded by the French Ministry of Health. Dr Bonello has received research grants from AstraZeneca and honoraria from AstraZeneca, Boston Scientific, Abbott, and Biotronik. Dr Montalescot has received institutional research grants or consulting/lecture fees from Abbott, Amgen, Actelion, AstraZeneca, Bayer, Boehringer Ingelheim, Boston-Scientific, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Cardiovascular Research Foundation, Daiichi-Sankyo, Idorsia, Lilly, Europa, Elsevier, Fédération Française de Cardiologie, ICAN, Medtronic, Journal of the American College of Cardiology, Lead-Up, Menarini, MSD, Novo-Nordisk, Pfizer, Sanofi, Servier, the Mount Sinai School, TIMI Study Group, and WebMD. Dr Valentine has disclosed no relevant financial relationships.

American Heart Association (AHA) Scientific Sessions 2018. LBS.04, Abstract 19343, presented November 11, 2018.

N Engl J Med. 2013;369:999-1010. Full text

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