Considerations for Pretreatment in PCI for NSTE-ACS

 An interventional cardiologist’s treatment strategies

What is your approach to assessing a patient with acute coronary syndrome?

Acute coronary syndrome (ACS) encompasses a broad patient population that may involve a variety of clinical scenarios. As we know, the potential of high-risk sequelae in ACS makes it imperative to utilize a thoughtful approach when treating these patients. Prior to invasive treatment, an assessment of the patient’s clinical acuity of presentation, risk factors, and current cardiac function is useful to assist in decision making. In terms of initial presentation, it may be useful to use risk stratification tools that include factors to understand cardiac risk, such as the GRACE 2.0 score. This allows us to provide an algorithm for the timing of invasive strategy.

How does the coronary anatomy influence your interventional approach?

Once we complete a coronary angiogram and invasive hemodynamic assessment, we are able to evaluate the anatomical and intravascular characteristics, which may or may not require hemodynamic support. Furthermore, we then can classify the myocardium at risk, depending on where the culprit lesion is located and if there is high-risk lesion morphology such as calcification, tortuosity, bifurcation, eccentricity, long lesions, and multiple tandem lesions. Lastly, we evaluate the required interventional strategy, whether it’s mechanical or aspiration thrombectomy, rotational, orbital, and laser atherectomy, lithotripsy, balloon angioplasty, and/or stenting. The various combinations all confer a different risk-time potential when intervening in the intravascular space, which is inherently thrombogenic. All these factors need to be considered to predict what’s necessary for treating the patient in a comprehensive and thoughtful way.

The decision for pretreatment usually depends on the clinical timeline. If a decision is made to take the patient directly to the catheterization laboratory due to a suspected case of ACS, then it is reasonable to withhold pretreatment with oral P2Y₁₂ inhibition and consider therapies after coronary anatomy is identified. This strategy is rational given the time required for oral P2Y₁₂ inhibitor uptake and therapeutic benefit.

What do the guidelines say about pretreatment with a P2Y₁₂ inhibitor for NSTE-ACS?

The discussion of pretreatment with a P2Y₁₂ inhibitor is centered around the invasive strategy, timing, and clinical scenario. Early studies found that pretreatment can reduce the outcome of CV death, MI, or urgent-target vessel revascularization.^1,2 More recent studies have shown that pretreatment increases bleeding risk without any survival benefit or a reduction in ischemic events.³ The idea of pretreatment has changed and really should be applied on a case-by-case basis.

The current 2021 ACC/AHA/SCAI Guideline for coronary artery revascularization does not confirm whether an oral P2Y₁₂ inhibitor should be given as pretreatment prior to PCI; the supportive text refers to the conflicting data and suggests that in current practice, loading after the anatomy is known may offer a similar benefit to preloading.⁴

The 2020 European Society of Cardiology (ESC) Guidelines for NSTE-ACS say that pretreating with a P2Y₁₂ receptor inhibitor may be considered for patients who are not expected to undergo an early invasive strategy and do not have a high bleeding risk.⁵ I think the understanding is that in some cases, a patient can be admitted with NSTEMI or unstable angina who presents with stable blood work and symptoms that are under control and may not undergo an early invasive strategy until many hours or even days later. When a delayed invasive strategy is chosen, it may be reasonable to initiate oral P2Y₁₂ receptor inhibition.

What do you think about the use of a parenteral antiplatelet agent, such as KENGREAL^® (cangrelor)?

The most current US Guideline referenced earlier also states that for patients undergoing PCI who are P2Y₁₂ inhibitor naive, intravenous KENGREAL (cangrelor) may be reasonable to reduce periprocedural ischemic events.⁴ I think this is extremely valuable, because years ago we did not have an IV P2Y₁₂ option for antiplatelet therapy. Now we’re armed with KENGREAL for patients who were not previously started on P2Y₁₂ inhibition. The efficacy and safety of KENGREAL were demonstrated in the 10,942-patient CHAMPION PHOENIX trial.⁶

Two important matters to consider are timing and onset of effect—more specifically when the patient is being preloaded and when the patient will experience the therapeutic window of the medication. The various oral P2Y₁₂ inhibitor medications have their own pharmacokinetics which relate to different therapeutic onset of their antiplatelet effects. There are some other medications that may be administered during an ACS event that can affect the uptake and timing of oral P2Y₁₂ inhibitors. For example, opioids such as morphine and fentanyl have been shown to delay and reduce the absorption of oral P2Y₁₂ inhibitors, and most US PCI patients routinely receive fentanyl as part of conscious sedation.^7-10

Without critically important information about the coronary anatomy until angiography, preloading with an oral P2Y₁₂ inhibitor in some cases may be premature and hinder our decision-making ability, especially in the urgent NSTEMI setting requiring multivessel coronary artery bypass grafting. The PK/PD profile of KENGREAL makes it an important drug to have on hand. It has a rapid onset of action within 2 minutes, an average elimination half-life of 3-6 minutes, and a quick offset within an hour of discontinuation.¹¹

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Important Safety Information

KENGREAL^® (cangrelor) for Injection is contraindicated in patients with significant active bleeding.

KENGREAL^® is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to cangrelor or any component of the product.

Please see below for Full Important Safety Information

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For what situations have you found KENGREAL^® (cangrelor) to be a good option?

I have used KENGREAL in many clinical scenarios. In one of my recent cases, a patient presented with cardiogenic shock and Grade 5 thrombus in the left anterior descending (LAD) artery that required a longer procedure with complex bifurcation PCI. The patient was intubated and could not be given an oral medication acutely without orogastric placement. KENGREAL was started, and eventually the patient had an oral gastric tube placed at the end of the procedure. It should be noted that randomized controlled trials have not been conducted to evaluate the safety and efficacy of KENGREAL in patients with cardiogenic shock.

I also look at the acuity of the case and the interventional strategy required to complete the coronary intervention. Moreover, I look at complexities within the high-risk anatomy, such as thrombus characteristics and bifurcations. When there are chronic occlusions, KENGREAL allows the flexibility to turn on antiplatelet therapy when the decision is made to proceed with intervention. In other cases, when there is a highly thrombotic lesion, I’ve noticed fewer sequelae of the thrombus.

So overall, in terms of coronary anatomy, I look to use KENGREAL when there is high thrombus burden, bifurcations, long lesions above 20 mm in length and less than 2.5 mm in diameter, chronic total occlusions, multiple tandem lesions, severe tortuosity or eccentricity, and heavily calcified arteries. KENGREAL also works well in PCI when patients cannot take or reliably absorb oral medication. If the patient has received coadministration of opioids, these are known to interfere with oral P2Y₁₂ absorption.^7-10 KENGREAL’s flexibility afforded by the 2-minute onset and 1 hour offset allows me to make the right clinical decisions for the patient.¹¹ I think that separates KENGREAL from other options. 

Indication

KENGREAL^® (cangrelor) for Injection is a P2Y platelet inhibitor indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.

Important Safety Information 

KENGREAL (cangrelor) for Injection is contraindicated in patients with significant active bleeding.

KENGREAL is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to cangrelor or any component of the product.

Drugs that inhibit platelet P2Y function, including KENGREAL, increase the risk of bleeding. In CHAMPION PHOENIX, bleeding events of all severities were more common with KENGREAL than with clopidogrel. Bleeding complications with KENGREAL were consistent across a variety of clinically important subgroups. Once KENGREAL is discontinued, there is no antiplatelet effect after an hour.

The most common adverse reaction is bleeding.

Please see Full Prescribing Information 

References: 1. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358(9281):527-533. 2. Steinhubl SR, Berger PB, Mann JT, III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial [published correction appears in JAMA. 2003;289(8):987]. JAMA. 2002;288(19):2411-2420. 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. 4. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2021;00:000-000. 5. 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. 6. Bhatt DL, Stone GW, Mahaffrey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303-1313. 7. Ibrahim K, Shah R, Goli RR, et al. Fentanyl delays the platelet inhibition effects of oral ticagrelor: full report of the PACIFY randomized clinical trial. Thromb Haemost. 2018;118(8):1409-1418. 8. BRILINTA^® (ticagrelor) Prescribing Information, Astra-Zeneca, 2022. 9. PLAVIX^® Prescribing Information, Bristol-Myers Squibb/Sanofi 2022. 10. EFFIENT^® (prasugrel) Prescribing Information, Eli Lilly and Co, 2022. 11. KENGREAL^® (cangrelor) Prescribing Information. 2022.

KENGREAL^® is a registered trademark of Chiesi Farmaceutici, S.p.A.

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