A 66-year-old male patient presented to your office for evaluation of chest discomfort. He described his symptoms, which began approximately 3 weeks ago, as a pressure associated with shortness of breath that occurred with moderate exertion such as walking up hills or a flight of steps. Symptoms were relieved spontaneously within 5 minutes with rest. However, in the few days prior to his visit with you, he noticed symptoms were occurring with less exertion and were more intense and lasted longer, prompting him to use his old sublingual nitroglycerin twice in the last 2 days. He did not report rest angina.
His medical history was notable for hypertension, prior myocardial infarction with previous stenting to the right coronary artery, diabetes, and increased cholesterol. Current medications included aspirin 81 mg daily, metoprolol succinate 25 mg daily, amlodipine 5 mg daily, metformin 500 mg twice daily, and pravastatin 40 mg daily. His physical exam demonstrated a blood pressure of 148/75 mmHg, heart rate of 74 bpm, and respiratory rate of 16. The remainder of the physical exam was normal. Admission laboratory results were notable for a creatinine of 1.6 mg/dl with a creatinine clearance of 46 ml/min, hemoglobin of 11.5 g/dl (normal range 13.2-17), white blood cell count of 11 10e9 (upper range of normal 9.7 10e9 ), high-density lipoprotein of 45 mg/dL, low-density lipoprotein of 70 mg/dL, and hemoglobin A1c of 7.1%. His electrocardiogram showed mild lateral ST depression with left ventricular hypertrophy changes. You subsequently ordered stress myocardial perfusion imaging, which was performed the next day. He exercised for 3 minutes on a Bruce protocol before developing substernal chest discomfort and 2 mm of ST depression. Symptoms resolve in recovery within 5 minutes. Imaging demonstrates a large, moderate- to high-grade, mostly reversible anterior defect accounting for approximately 20% of the left ventricle. Ejection fraction was 55% at rest, decreasing to 45% post stress. Given the frequency of angina, the fact that it occurred at such a low workload, and that he was currently on 2 antianginals, the decision was made to proceed with coronary angiography, which was performed the next day. This demonstrated an 80% proximal left anterior descending artery stenosis involving the origin of the diagonal, 40% mid left circumflex lesion, and a 50% proximal right coronary artery lesion proximal to the prior patent stent. Successful stenting of bifurcating left anterior descending/D1 lesion was performed using the double kiss crush technique. Two second-generation everolimus-eluting stents were employed with total stent length of 40 mm. Pravastatin was changed to atorvastatin 80 mg, and he was subsequently discharged with aspirin and ticagrelor in addition to his other medications.
He follows up with you at 1 and 3 months and has not had recurrent chest pain. However, he notes that when he cuts himself shaving, it often takes a half an hour to stop bleeding.
Based on the TWILIGHT COMPLEX (Ticagrelor With Aspirin or Alone in High-Risk Patients After Complex Percutaneous Coronary Intervention) study, which of the following would be appropriate?
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The correct answer is: D. Stop the aspirin but continue ticagrelor 90 mg twice daily
Using data from eight different trials, the PRECISE DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) bleeding score was developed and validated.1 An online calculator is currently available: http://www.precisedaptscore.com/predapt/webcalculator.html. This patient has a PRECISE DAPT bleeding score of 35, indicating a high risk for bleeding with an estimated 12-month risk of Thrombolysis in Myocardial Infarction major bleeding of 1.9% and Thrombolysis in Myocardial Infarction major or minor bleeding of 3.8%.
Bleeding is not uncommon among patients treated with dual antiplatelet therapy (DAPT), may not always be reported to the clinician, and may contribute to early DAPT discontinuation.2
This was a post-hoc analysis of the complex percutaneous coronary intervention (PCI) cohort (n = 2,342 patients) in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial examining the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing complex PCI. Complex PCI was defined as any of the following: 3 vessels treated, ≥3 lesions treated, total stent length >60 mm, bifurcation with 2 stents implanted, atherectomy device use, left main PCI, surgical bypass graft, or chronic total occlusion as target lesions. In patients who initially completed 3 months of ticagrelor plus aspirin, continuation of ticagrelor monotherapy was associated with lower incidence of BARC type 2, 3, or 5 bleeding (4.2% vs. 7.7%; hazard ratio 0.54; 95% confidence interval, 0.38-0.76) without increasing the risk of ischemic events (death, myocardial infarction, or stroke; 3.8% vs. 4.9%; hazard ratio 0.77; 95% confidence interval, 0.52-1.15) or in-stent thrombosis.
These data suggest that risk of bleeding can be reduced by a strategy of ticagrelor monotherapy, following 3 months of DAPT, without incurring any increased risk of ischemic events even among patients undergoing complex PCI. Because this was a post-hoc analysis, additional dedicated prospective studies are needed to establish optimal antithrombotic strategies with favorable risk-benefit trade-off between bleeding and ischemic complications among patients who undergo complex PCI. Recent data from the TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) trial indicates that a treatment-similar strategy is effective.5
Choice A would be correct based on current guidelines but puts the patient at increased risk of bleeding. Choice B would be reasonable after 1 year based on the results of the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial. Choice C would be reasonable if the patient developed bleeding; however, decreasing bleeding risk by changing to ticagrelor alone would be a better alternative.
References
Costa F, van Klaveren D, James S, et al. Derivation and Validation of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) Score: A Pooled Analysis of Individual-Patient Datasets From Clinical Trials. Lancet 2017;389:1025-34.
Wang TY, McCoy L, Henry TD, et al. Early Post-Discharge Bleeding and Antiplatelet Therapy Discontinuation Among Acute Myocardial Infarction Patients Treated With Percutaneous Coronary Intervention. J Am Coll Cardiol 2014;63:1700-2.
Mehran R, Baber U, Sharma SK, et al. Ticagrelor With or Without Aspirin in High-Risk Patients After PCI. N Engl J Med 2019;381:2032-42.
Dangas G, Baber U, Sharma S, et al. Ticagrelor With or Without Aspirin After Complex PCI. J Am Coll Cardiol 2020;75:2414-24
Kim BK, Hong SJ, Cho YH, et al. Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial. JAMA 2020;323:2407-16.