NSTE-ACS: Did we aDAPT too soon?

Figure 1. NSR, tachycardic. ST segment depression in leads I, II, V4-6. Potentially indicative of subendocardial ischemia of LMCA.

Case

67-year-old male with a chest pain.

- Past Medical History of T2DM, HTN, current smoking, and hyperlipidemia

- Substernal “pressure” 4 hours ago, radiating to left arm, exertional, non-pleuritic

- Given aspirin and nitroglycerin in route to the hospital

- Chest pain relieved by rest and nitroglycerin

- ROS: + dizziness, diaphoresis, SOB

- Has never had a coronary catheterization

Initial troponin: 0.24, Three-hour troponin: 0.18

He was diagnosed with an NSTE-ACS with plan to obtain cardiac catheterization. The expectation is that this patient will continue for treatment with PCI. The question arose of whether to load him with P2Y12 receptor inhibitors before cardiac catheterization.

Clinical Question

Should patients without atrial fibrillation and unknown coronary anatomy with NSTE-ACS be given P2Y12 receptor inhibitor treatment before diagnostic cardiac catheterization (“pre-treating”)?

Summary of the evidence

- Treatment of NSTE-ACS with aspirin plus P2Y12 receptor inhibitors prior to cardiac catheterization was believed improve outcomes due to increased platelet inhibition, but there have been no large-scale trials to support pre-treatment strategies1,2

- P2Y12 receptor inhibitors have very long offsets, which delays surgical intervention

Table 1. Onset, offset, and delay to surgery timelines for common P2Y12 inhibitors

- ACCOAST trial (n=4,033): RCT of patients with a positive troponin, diagnosed with NSTE-ACS, scheduled for coronary angiography within 48 hours.

o Compared pre-treatment with 30mg loading dose of prasugrel before angiography with placebo. Primary endpoint of a composite of death from cardiovascular causes, MI, CVA, or urgent revascularization through day 7, secondary assessment of bleeding risk

o If PCI was indicated, the pre-treatment group received 30mg prasugrel and the placebo group was given 60mg directly before PCI

o No ischemic benefit of pre-treatment (HR = 1.02, 0.84-1.25) with increased bleeding risk within 7 days (HR = 1.90, 1.19-3.02)3

- SCAAR trial (n=64,857): Observational data comparing pre-treatment with ticagrelor, clopidogrel, or prasugrel against no pre-treatment in patients diagnosed with NSTE-ACS

o Pre-treatment with any P2Y12 receptor inhibitor provided no mortality benefit at 30 days (OR = 1.17, 0.66-2.09) or 1 year (OR = 0.96, 0.56-1.63) but increased in-hospital bleeding risk (OR = 1.41, 1.01-2.01)4

- ISAR-REACT5 trial (n=4,018): Randomized, open-label trial in patients with ACS, with or without ST-segment elevation, comparing pre-treatment with ticagrelor and treatment with prasugrel directly prior to PCI.

o Post-catheterization treatment with prasugrel was found to be superior to ticagrelor as pre-treatment with ticagrelor lead to increased incidence of death, MI, or stroke at one year (HR = 1.36, 1.09 – 1.70)5

o No difference in bleeding risk between the two treatments (HR = 1.12, 0.83-1.51)

Recommendations

1. Given the lack of evidence-based ischemic benefit, the increased risks of bleeding, and the potential to delay procedural treatment (e.g. CABG), empiric P2Y12 receptor inhibitor loading should not be done prior to coronary catheterization for patients with concern for NSTE-ACS and unknown coronary anatomy.

2. Given the rapid onset of prasugrel and ticagrelor, they can be given after diagnostic coronary angiography and directly before PCI.

References

1. Sibbing D, Kastrati A, Berger PB. Pre-treatment with P2Y12 inhibitors in ACS patients: Who, when, why, and which agent? Eur Heart J. 2016;37(16):1284-1295. doi:10.1093/eurheartj/ehv717

2. Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42(14):1289-1367. doi:10.1093/eurheartj/ehaa575

3. Montalescot G, Bolognese L, Dudek D, et al. Pretreatment with Prasugrel in Non–ST-Segment Elevation Acute Coronary Syndromes. N Engl J Med. 2013;369(11):999-1010. doi:10.1056/nejmoa1308075

4. Dworeck C, Redfors B, Angerås O, et al. Association of Pretreatment with P2Y12 Receptor Antagonists Preceding Percutaneous Coronary Intervention in Non-ST-Segment Elevation Acute Coronary Syndromes with Outcomes. JAMA Netw Open. 2020;3(10):2018735. doi:10.1001/jamanetworkopen.2020.18735

5. Schüpke S, Neumann F-J, Menichelli M, et al. Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2019;381(16):1524-1534. doi:10.1056/nejmoa1908973