Cangrelor Bridge for Repeat Cesarean After Third Trimester Percutaneous Coronary Intervention for Total Occlusion NSTEMI

ABSTRACT

Acute coronary syndrome is an uncommon but potentially life‐threatening complication in pregnancy, and dual antiplatelet therapy presents challenges in patients requiring cesarean delivery. We present a 39 year‐old woman who presented at 29 weeks gestation with a non‐ST segment myocardial infarction (NSTEMI). Urgent coronary angiogram revealed 100% occlusion of the left anterior descending coronary artery. She underwent percutaneous coronary intervention (PCI) with one drug‐eluting stent and was initiated on dual antiplatelet therapy. Due to prior classical cesarean delivery, she required repeat cesarean less than 3 months from PCI. Cangrelor was used as bridging therapy prior to cesarean delivery at 37 weeks gestation to balance the thrombotic and bleeding risks. This case underscores the importance of recognizing total coronary occlusion in NSTEMI presentations and is, to our knowledge, the first reported use of intravenous cangrelor as perioperative bridging therapy for cesarean delivery in a pregnant patient with recent PCI for acute coronary syndrome.

Key Clinical Message

Severe chest pain and elevated troponin should raise suspicion for total occlusion myocardial infarction regardless of EKG findings. Furthermore, this case underscores the value of individualized antiplatelet management in pregnancy and highlights the use of intravenous cangrelor as perioperative bridging therapy to facilitate cesarean delivery after recent percutaneous coronary intervention.

Visual Summary, case timeline of non‐ST‐elevation MI with PCI followed by cangrelor bridge for classical cesarean delivery.

1. Introduction

Maternal myocardial infarction is responsible for approximately 20% of all pregnancy related cardiovascular deaths [1]. While ST‐elevation myocardial infarction (STEMI) is more readily recognized, total coronary artery occlusions may present without ST‐segment elevation, manifesting as non‐ST elevation myocardial infarction (NSTEMI) [2], which can pose diagnostic challenges and delay appropriate intervention.

Duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) during pregnancy is not well established [3, 4]; thus, scenarios where interruption of DAPT is unavoidable, such as with prior cesarean delivery (CD), bridging strategies require a balance of thrombotic and bleeding risk. While use of cangrelor for perioperative bridging and during percutaneous coronary intervention (PCI) has been well described; in comprehensive literature review (Appendix S1), cangrelor use in pregnancy has only been documented once in a non‐coronary context involving a patient with a cerebral stent [5, 6].

We present a rare case of total occlusion of the left anterior descending coronary artery (LAD) presenting as NSTEMI in a pregnant patient, successfully managed with PCI followed by the first reported use of cangrelor for perioperative bridging for CD.

2. Case History

The patient is a 39 year‐old woman, pregnant at 29 weeks gestation (G2P0101; 1 prior preterm birth) who presented to the emergency department with severe, acute onset crushing chest pain. Her systolic blood pressures ranged between 140 and 160 mmHg; she was mildly tachycardic, with oxygen saturation 100% on room air. On exam she was diaphoretic and in moderate distress. Sublingual nitroglycerin did not improve symptoms, and hypertension was treated with intravenous labetalol. Given her critical presentation and multiple medical comorbidities, she underwent expedited cardiac evaluation.

Pertinent past medical history included systemic lupus erythematosus with nephritis, chronic hypertension, and class III obesity. Additionally, she met criteria for obstetric antiphospholipid antibody syndrome (due to prior beta 2 glycoprotein antibody, early onset fetal growth restriction and prior preterm birth; no prior thromboembolic disease), and thus was treated with prophylactic dose low molecular weight heparin (LMWH) during pregnancy based on consensus recommendations [7, 8]. Due to multiple risk factors for pre‐eclampsia, she was prescribed aspirin. Importantly, her obstetric history was notable for prior classical CD and uterine myomectomy.

2.1. Differential Diagnosis, Investigations, Treatment

Laboratory testing revealed a normal brain natriuretic peptide and elevated high sensitivity troponin that increased over 4 h from 246 ng/L to 1216 ng/L (reference range < 34 ng/L). Transthoracic echocardiogram on admission revealed segmental dysfunction of the anteroseptal and apical walls resulting in mild systolic dysfunction, with a biplane left ventricular ejection fraction of 43%. Serial electrocardiograms (EKGs) revealed nonspecific ST and T wave changes without evidence of an ST elevation (Figure 1). A non‐coronary chest computed tomography (CT) angiogram showed no evidence of an aortic dissection but did show calcifications and atherosclerosis of the mid‐distal LAD and a resting perfusion defect in the apical and anterior segments of the LAD (Figure 2).

FIGURE 1.

Electrocardiogram at presentation showing normal sinus rhythm with sinus arrhythmia, with nonspecific ST and T wave abnormalities and mild ST depressions.

FIGURE 2.

Noncoronary chest computed tomography angiography demonstrating resting perfusion defect in apical anterior myocardium (red arrows).

The patient had multiple risk factors for atherosclerosis and thrombosis including hypertension, class III obesity, and presence of lupus anticoagulant, raising suspicion ACS due to typical plaque rupture as the initial diagnosis. Aortic dissection, spontaneous coronary artery dissection, cardiomyopathy, and pulmonary embolism were initially considered, though they were deprioritized after imaging revealed no supporting findings. The patient's severe, unremitting chest pain made vasospastic angina less likely.

Considering her acute crescendo angina and persistent pain despite medical therapy, an urgent coronary angiogram was performed, revealing a 100% occluded LAD (Figure 3). The remainder of the coronary anatomy showed a ramus vessel with minimal luminal irregularities, a circumflex vessel which had minimal disease and gave rise to 3 obtuse marginal branches and a posterior descending artery. There was a small, non‐dominant right coronary artery and no collateral vessels visualized. Given the angiographic appearance, atherosclerotic risk factors and coronary calcifications visualized on CT scan (Figure 2), the LAD lesion was presumed to result from atherosclerotic plaque rupture. PCI was performed with a drug‐eluting stent (38 MM 3 MM Synergy XD Monorail 144 cm Everolimus) placed in the LAD and clopidogrel was added to her regimen of aspirin and prophylactic LMWH. Post procedure fetal monitoring was reassuring, and she was discharged on hospital day 4. Repeat echocardiography 6 weeks later showed normal left ventricular systolic function and she had no recurrence of chest pain.

FIGURE 3.

Emergent coronary angiogram with red arrows demonstrating 100% occlusion of left anterior descending coronary artery (left frame) and result post percutaneous coronary intervention (right frame).

Peripartum antiplatelet strategy: Due to prior classic CD, repeat cesarean at 37 weeks gestation was indicated, though this was only 8 weeks after PCI. After robust multidisciplinary discussions between clinicians in cardiology, pharmacy, and maternal fetal medicine, weighing the risks of thrombotic events with recent PCI in the LAD in the setting of ACS and bleeding risk of CD, the decision was made to utilize cangrelor as a bridge perioperatively, at the commonly described bridging dose of 0.75 mcg/kg/min.⁵ This allowed washout of clopidogrel to perform the CD on aspirin only due to the unique pharmacokinetic properties of cangrelor, limiting interruption of DAPT to only ~9 h. At 37 weeks gestation, the patient was admitted for perioperative medical optimization before planned repeat CD (Figure 4) and 5 days before planned delivery, clopidogrel and LMWH were stopped. Cangrelor was initiated 4 days prior to delivery (24 h after the last dose of clopidogrel) and used as a bridge, while monitoring daily platelet counts, until 3 h before the procedure when it was stopped. Six hours following the procedure after hemostasis was assured, clopidogrel was resumed (300 mg loading dose followed by 75 mg daily). LMWH was resumed on postpartum day 1 and continued for 6 weeks.

FIGURE 4.

Visual Summary, case timeline. HD = hospital day, w = weeks, d = days; NSTEMI = non‐ST‐elevation myocardial infarction, PCI = percutaneous coronary intervention, hrs = hours, D/C = discharge.

Delivery description: as above, the patient underwent repeat classic CD and additionally bilateral salpingectomy. Though there was adequate time free of antiplatelet and anticoagulants for neuraxial anesthesia, after a shared decision‐making discussion between the patient and anesthesiologist, the decision was made to proceed with general anesthesia for the procedure. Delivery and salpingectomy were performed via repeat Pfannenstiel incision. The patient remained hemodynamically stable during the procedure, and there were no problems with hemostasis. The estimated blood loss was 500 mL, with only a small hemoglobin drop from pre‐op (10 g/dL) to post‐op day 1 (9.2 g/dL). She remained stable throughout the hospitalization and her postpartum course was uncomplicated.

The newborn was small for gestational age with a birth weight of 2.1 kg and had APGAR scores at 1 and 5 min of 5 and 9, respectively. The newborn required non‐invasive respiratory support for 3 days in the neonatal intensive care unit and was discharged on room air and oral feeds. There were no neonatal bleeding complications.

2.2. Conclusion and Results

Four months following delivery, she had a cardiology follow‐up visit and did not have any cardiovascular complaints.

3. Discussion

3.1. Total Occlusion NSTEMI: Challenges in Diagnosis of ACS

Myocardial infarctions (MI) during pregnancy can be from multiple mechanisms, including spontaneous coronary artery dissection, coronary thrombosis, or vasospasm. In this case, anti‐phospholipid‐related thrombosis was also possible, though less likely given concomitant LMWH use. While MI secondary to atherosclerosis in pregnancy is rare, occurring in one in every 16,000 deliveries [1], this was presumed to be the etiology in our patient given atherosclerotic risk factors, coronary calcifications visualized on CT scan, and angiographic appearance. Intravascular ultrasound can be helpful to support the diagnosis in this clinical scenario, though it was deferred at the interventionalist's discretion.

Cases of total coronary artery occlusion presenting as NSTEMI i.e., characterized by elevated troponin without ST‐segment elevation, have been reported, though most involve the right or left circumflex coronary arteries [2]. Our case report highlights a unique clinical presentation of a total coronary artery occlusion of the LAD during pregnancy, presenting without ST elevation on EKG. Symptoms of severe chest pain and elevated troponin, regardless of EKG findings, should increase clinicians' suspicion not only for NSTEMI but also for total occlusion MI. In our patient's case, it can be hypothesized that her total occlusion did not present with classical ST‐elevation MI on EKG as the anterior wall was otherwise well supplied with multiple obtuse marginal branches from the left dominant system. It is notable that the CT scan obtained for evaluation of aortic dissection revealed a resting myocardial perfusion defect and highlights the importance of utilizing multimodal imaging.

3.2. Bridging Therapy: Cangrelor in Cesarean Delivery

Though this patient received PCI with a drug‐eluting stent, balloon angioplasty alone could be considered, which would mitigate the need for bridging antiplatelet therapy. However, the incidence of re‐stenosis in lesions treated with balloon angioplasty alone is up to 40%, with much lower rates after drug‐eluting stent placement [9]. In addition, current recommendations for PCI during pregnancy are to follow standard revascularization guidelines, and when coronary stent placement is indicated, a drug‐eluting stent should be utilized [10].

After PCI, antiplatelet agents are the cornerstone in the prevention of future cardiovascular events, but in times of unavoidable procedures, they may need to be discontinued days prior to prevent excessive bleeding. The evidence for use of DAPT after PCI in ACS is ever evolving. Guidelines at the time of this case recommended 1 year of DAPT in patients with ACS, though transition to P2Y12 inhibitor monotherapy “could be considered in select patients” at 1–2 months [11]. Though the most recent guidelines offer de‐escalation to monotherapy at 1 month in patients at high bleeding risk, including potentially aspirin alone, they note the “safety of these strategies in terms of their effects on risk of major adverse cardiac events is less firmly established.” [12] It is important to note the studies which led to these recommendations did not include pregnant patients and may not be generalizable to patients during pregnancy given the pro‐thrombotic state. Furthermore, there is no specific guidance on the optimal duration of DAPT after ACS during pregnancy [3]. Thus, cardiovascular care for the pregnant patient requires a patient‐specific and nuanced approach to balance maternal cardiovascular and obstetric risk [4]. Given this patient's concomitant lupus anticoagulant and recent ACS, the multidisciplinary team weighed the significant maternal risk of perioperative hemorrhage while continuing DAPT against the potentially catastrophic risk of acute stent thrombosis and recurrent myocardial infarction if antiplatelet therapy was interrupted. Ultimately, stopping DAPT before 6 months was felt to be too high risk. However, bleeding risk in CD was also significant, and the obstetric team felt it would be too unsafe to operate on DAPT. In this clinical setting, cangrelor was deemed to be an appropriate bridging therapy.

Cangrelor is the only intravenous P2Y12 inhibitor. Compared to clopidogrel (t1/2 = 6 h), cangrelor is a potent agent with a faster onset (2 min) and shorter half‐life (t1/2 = 3–6 min), providing rapid, robust antiplatelet coverage while having the advantage of relatively fast washout [13, 14]. While use for perioperative bridging and during PCI has been well described, its use in pregnancy has only been documented once for a patient with a cerebral stent [6]. Cangrelor is classified as an FDA pregnancy category C drug, indicating that the risk towards the fetus cannot be ruled out. The ability of cangrelor to cross the placenta or its impact on fetal bleeding is not well described due to its limited recorded use in pregnant patients; however, its molecular size and hydrophilicity make it potentially less favorable for placental transfer [6]. While there are no human studies of cangrelor in pregnancy, according to the manufacturer's prescribing information, it has not been shown to be teratogenic in animal studies with the exception of extremely high doses in rabbits [15]. Use in pregnancy is still widely cautioned and only to be used if risk exceeds potential benefit; therefore, this strategy should not be generalized to all pregnant patients. Given the paucity of data regarding the safety in pregnancy, cangrelor should only be considered after individualized multidisciplinary assessment with careful evaluation of ischemic, thrombotic, and bleeding risks.

In summary, this case highlights the importance of evaluating for total coronary artery occlusion in patients presenting with acute coronary syndrome with persistent chest pain without clear ST‐segment elevation. Furthermore, it underscores the complexity of antiplatelet management in pregnancy and the need to balance ischemic and bleeding risks in patients with recent ACS and PCI, particularly in the setting of elevated thrombotic risk due to an underlying hypercoagulable disorder. Based on a literature search, to our knowledge, this is the first reported use of intravenous cangrelor as perioperative bridging therapy for cesarean delivery in a pregnant patient with prior PCI for ACS.

Author Contributions

Vidya N. Mullangi: conceptualization, writing – original draft, writing – review and editing. Sara Folk: conceptualization, writing – original draft, writing – review and editing. Sneha Sharma: conceptualization, writing – original draft, writing – review and editing. Gillian Belnavis: conceptualization, supervision, writing – review and editing. Shea Macielak: conceptualization, supervision, writing – original draft, writing – review and editing. Danielle Blais: conceptualization, writing – original draft, writing – review and editing. Talal Attar: conceptualization, supervision, writing – review and editing. Blair Suter: conceptualization, writing – original draft, writing – review and editing. William H. Marshall V: conceptualization, supervision, writing – original draft, writing – review and editing.

Funding

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient for publication of this case report, including the accompanying images.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Appendix S1: Literature Review Examining the Use of Cangrelor as Bridging Therapy in Pregnancy.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.