Case Report: Triple Therapy in a Patient With High Bleeding Risk After PCI
For patients on chronic oral anticoagulation (OAC) who are undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT; aspirin and a P2Y12 inhibitor) is required to prevent stent thrombosis. However, combining DAPT with OAC increases the risk of bleeding. It remains unclear whether these patients on chronic OAC undergoing PCI should be treated with DAPT; it can be problematic if surgery is required or if a bleeding complication occurs. In the following case report, optimal anticoagulant and antiplatelet treatment will be discussed, as well as the management of gastrointestinal (GI) bleeding while on antithrombotic treatment.
An 81-year-old man was admitted to our hospital due to exertional dyspnea and chest pain that had been manifesting for several months. The patient had multiple coronary risk factors, including hypertension, dyslipidemia, glucose intolerance, family history of coronary disease, and he was an active smoker. Laboratory data revealed mild anemia (hemoglobin, 9.8 g/dL), and the platelet level remained within the normal range (platelets, 267 X 103 cells/μL). His renal function testing results were blood urea nitrogen, 17.6 mg/dL; creatinine, 1.1 mg/dL; and estimated glomerular filtration rate (eGFR), 54.2 mL/min/m2. He was on anticoagulation therapy (2.5 mg b.i.d. apixaban) for chronic atrial fibrillation. His left ventricular ejection fraction was 60% with echocardiographic evaluation. The exercise stress test revealed downsloping ST-segment depression in leads V4 through V6 on electrocardiography. The patient was diagnosed with effort angina pectoris and underwent coronary angiography, which revealed tight stenosis in the right coronary artery (RCA) (Figure 1A), and no significant narrowing in the left coronary artery.
To treat his lesion in the RCA, PCI was performed for revascularization via a left radial approach with optical coherence tomography (OCT) guidance. This patient began to take medication 1 week before admission for PCI, including 100 mg aspirin, 75 mg clopidogrel, and proton pump inhibitor, in addition to the novel oral anticoagulant apixaban. Predilatation with a 3- X 13-mm noncompliant balloon was performed, and then a 3- X 33-mm XIENCE everolimus-eluting stent (Abbott) was implanted in the RCA, inflated at 18 atm (Figure 1B). After postdilation at 20 atm with the same predilatation balloon, the lesion was well dilated and stented on angiography (Figure 1C). OCT confirmed optimal strut apposition and full expansion of the stent in the treated segment (Figure 2), and the procedure was successfully finished.
Seven days after the procedure, the patient developed hematemesis that caused acute blood loss anemia. The hemoglobin level was decreasing from 9.8 g/dL to 6.2 g/dL, and he required 4 units of red blood cell transfusion. An urgent gastroscopy revealed advanced gastric cancer in the entire circumference of the gastric wall on the pyloric side (Figure 3). In order to prevent more bleeding, all antithrombotic drugs were immediately stopped, and heparin was administered instead. Urgent partial gastrectomy was required due to the risk of occlusion in the GI tract. Fourteen days after PCI, partial gastrectomy was performed with a Roux-en-Y anastomotic reconstruction. Since then, there has been no progression of anemia, and apixaban and clopidogrel were restarted 7 days after the gastrectomy. On postoperative day 18, the patient was discharged without any cardiac complications.
In this case, a severe GI bleeding complication occurred under the antithrombotic therapy combining OAC with DAPT (known as triple therapy). Triple therapy increases the risk of bleeding two- to three-fold. Another consideration is whether to omit aspirin in patients who require triple therapy. The WOEST study is the first published randomized controlled trial that has investigated dual therapy (vitamin K antagonist and clopidogrel) in comparison with triple therapy.1 In this case, we discontinued aspirin indefinitely, following this evidence.
The most common reason for premature discontinuation of antithrombotic therapy after PCI is the manifestation of GI bleeding. Sueta et al reported clinical significance of fecal occult blood screening in patients before PCI.2 In this case, PCI was performed as an elective procedure. Laboratory data revealed existence of anemia before PCI, therefore, we had enough time to perform and check a fecal occult blood test. When anemia of a patient is revealed before PCI, performing subsequent fecal occult blood testing may prevent GI bleeding. If fecal occult blood testing is positive, gastroscopy should be performed before PCI.
OCT is a high-resolution intravascular imaging modality that enables evaluation of the immediate result of PCI, particularly those of stent implantation. Thus, OCT can analyze and measure the residual lumen, the degree of stent expansion, complete apposition of its struts to the vessel wall, the existence of intrastent prolapse, and the development of dissections.3 In this case, optimal stenting results of the XIENCE DES were confirmed with OCT evaluation. The XIENCE DES has been associated with the lowest rates of stent thrombosis4,5; therefore, we felt comfortable disrupting antithrombotic drugs when needed in this case without a growing concern for stent thrombosis.
It is not yet known what the optimal post-PCI antithrombotic therapy is for patients on chronic OAC. More evidence is needed in the form of randomized controlled trials.
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1. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107-1115.
2. Sueta D, Hokimoto S, Tayama S, et al. Clinical significance of fecal occult blood screening in patients before percutaneous coronary intervention. Int J Cardiol. 2015;182:85-87.
3. Kim IC, Yoon HJ, Shin ES, et al. Usefulness of frequency domain optical coherence tomography compared with intravascular ultrasound as a guidance for percutaneous coronary intervention. J Interv Cardiol. 2016;29:216-224.
4. Natsuaki M, Morimoto T, Yamamoto E, et al. One-year outcome of a prospective trial stopping dual antiplatelet therapy at 3 months after everolimus-eluting cobalt-chromium stent implantation: ShortT and Optimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent (STOPDAPT) trial. Cardiovasc Interv Ther. 2016;31:196-209.
5. Watanabe H. One-month dual antiplatelet therapy followed by clopidogrel monotherapy versus standard 12-month dual antiplatelet therapy with clopidogrel after drug-eluting stent implantation: STOPDAPT-2. Presented at: ACC 2019; March 16-18, 2019; New Orleans, Louisiana.
Yoshihisa Nakagawa, MD, PhD
Professor and Chairman
Department of Internal Medicine
Division of Cardiovascular Medicine
Shiga University of Medical Science
Disclosures: Advisory board member for Abbott Vascular Japan.