Impact of Bleeding on Myocardial Infarction,Stroke, and Death During 12 Months Dual Antiplatelet Therapy After Acute Coronary Syndrome

BackgroundBleeding remains a complication during dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). Some data suggest a link between bleeding and worsened vascular outcomes. However, this association is unclear, due to omitting of minor bleedings when applying conservative scales. In contrast, the Platelet Inhibition and Outcomes (PLATO) trial classification used broad realistic capturing of all bleedings.MethodsAccess was gained to the Food and Drug Administration-issued adjudication data set on which post hoc analyses of bleeding, myocardial infarction (MI), stroke, and death were conducted. Bleeding was defined as minimal, minor, major, and life-threatening or fatal (LTOF) as per the original PLATO scale.ResultsAmong 18,624 enrollees, 10,705 adjudicated events occurred across 7171 patients. There were 618 minimal, 1412 minor, 1216 major, and 536 LTOF bleedings for the total of 3782 events reported in 3387 patients. There were 938 deaths, 2751 MIs and 359 strokes. The overall bleeding was 20.3%, exhibited in 19.2% patients. Total bleeds were associated with less deaths (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.47-0.63) and MI (OR: 0.47, 95% CI: 0.41-0.54; P < .001 for both). There were no differences in deaths (OR: 1.11, 95% CI: 0.93-1.34; P = .24), but less MIs (OR: 0.72. 95% CI: 0.59-0.86; P < .001), and more strokes (OR: 2.17, 95% CI: 1.64-2.88; P < .001) after LTOF. Major, minor, and minimal bleeds were associated with less deaths and MI but not strokes.ConclusionThese large uniformly adjudicated data reveal that within 12 months of dual antiplatelet therapy, 1 out of 5 patients experiences bleeding. Overall, bleeding was associated with diminished incidence of death and MI but not strokes.     

Optimal Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: Insights From a Network Meta-Analysis of Randomized Trials

BackgroundWith newer generation drug eluting stents (DES), the minimal duration of dual antiplatelet therapy (DAPT) recommended by guidelines has been reduced to 6 months in patients with stable coronary artery disease. Whether shorter duration of DAPT is safe in patients presenting with acute coronary syndrome (ACS) remains controversial. Our aim of this study was to investigate the optimal DAPT duration (≤3 months vs. 6 months vs. 12 months vs. >12 months) among patients with ACS undergoing percutaneous coronary intervention (PCI).MethodsPUBMED and EMBASE were searched through January 2020 for randomized controlled trials of DAPT duration in patients with ACS. The ischemic outcomes were all-cause death, myocardial infarction, and stent thrombosis. The safety outcome was major and/or clinically relevant bleeding.ResultsOur search identified 14 eligible trials enrolling a total of 31,837 patients comparing different DAPT duration in patients with ACS. Short-term DAPT (≤3 months or 6 months) did not increase ischemic outcomes compared to long-term DAPT (12 months and >12 months). For bleeding outcomes, ≤3 months DAPT was associated with significant reduction in bleeding compared to 6 months, 12 months or >12 months DAPT (OR [95% CI]: 0.60 [0.37–0.98]; 0.68 [0.54–0.85] and 0.43 [0.34–0.54], respectively). These findings were similar when limited to 2nd generation DES.ConclusionsData from this meta-analysis of randomized trials support short-term (≤3 months and 6 months) DAPT in patients with ACS undergoing PCI. Guidelines might need to consider short-term DAPT even in patients presenting with ACS, especially in this era of newer generation DES.     

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention

BackgroundDiabetes was reported to be associated with an impaired response to clopidogrel.ObjectivesThe aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).MethodsA subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.ResultsThere were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P_interaction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P_interaction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P_interaction = 0.19).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)     

Duration of Dual Antiplatelet Therapy in Patients with an Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Background

The recent American Heart Association/American College of Cardiology guidelines on duration of dual antiplatelet therapy (DAPT) recommend DAPT for 1 year in patients presenting with an acute coronary syndrome, with a Class IIb recommendation for continuation. We aim to assess the evidence for these recommendations using a meta-analytic approach.

PRECISE-DAPT评分对急性冠状动脉综合征合并糖尿病患者双联抗血小板治疗后出血风险的预测价值

目的探讨PRECISE-DAPT评分对接受经皮冠状动脉介入手术(PCI)的急性冠状动脉综合征(ACS)合并糖尿病(DM)患者双联抗血小板(DAPT)治疗后出血风险的预测价值。方法选择ACS合并DM患者200例,PCI术后接受DAPT治疗,随访时间为1年,记录出血事件发生情况,根据是否发生出血事件分为出血组和未出血组,评价PRECISE-DAPT评分对出血事件的预测价值。结果 (1)随访期间共有66例(33. 00%)发生出血事件,最常见为消化道出血,出血组平均年龄、年龄 65岁比例和治疗前PRECISE-DAPT评分高于未出血组(P 0. 05);(2) PRECISEDAPT评分与出血事情呈正相关(r=0. 63,P 0. 01),出血发生率随着PRECISE-DAPT评分分级增加而升高,其中≥25分组出血发生危险是≤10分组的5. 76倍(P 0. 05);(3) PRECISE-DAPT评分对于出血风险预测的最佳截断点为16. 84,其曲线下面积(AUC)为0. 71(Z=5. 60,P 0. 05,95%CI=0. 53～0. 85),此时的诊断敏感度为82. 27%,特异度为64. 09%,阳性预测值为86. 27%,阴性预测值为55. 73%,准确率为73. 37%。结论 ACS合并DM患者接受PCI术后出血患者的PRECISE-DAPT评分明显升高,该评分对于出血事件有一定的预测价值。     

Role of Antiplatelet Therapy in Secondary Prevention of Acute Coronary Syndrome

Cardiovascular disease is one of the major causes of death in developed countries, mainly related to coronary artery disease and its acute complications. Platelets play a great role in the pathogenesis of acute thrombotic events of coronary artery disease when silent chronic disease becomes acutely symptomatic. Platelet importance in coronary artery disease and pathophysiology of acute events support the large benefit of antiplatelet agents for both acute management of ACS and secondary prevention. Recent developments in oral antiplatelet therapy raised questions about the choice of the molecules, the use of single or double therapy, and the optimal dosing and duration of treatment. The present review aims to provide a current appraisal of antiplatelet therapy use after ACS and to summarize available scientific evidence for an optimal use of antiplatelet agents in daily practice, including the new P2Y12 blockers.     

Antiplatelet Therapy and Coronary Artery Bypass Grafting: Analysis of Current Evidence With a Focus on Acute Coronary Syndrome

This review was undertaken to summarize and discuss the current evidence around antiplatelet therapy and coronary artery bypass grafting (CABG). Aspirin (ASA) monotherapy remains the standard of care among patients before and after CABG. The role of more intense antiplatelet therapy—specifically, P2Y12 inhibitors—in improving clinical outcomes and graft patency is becoming increasingly apparent. As such, we provide an overview of a variety of antiplatelet regimens. The review discusses the evidence around preoperative management of antiplatelet therapies, with a particular focus on timing of cessation. It also evaluates the current literature to elucidate the best antiplatelet therapy regimen after CABG, focusing on acute coronary syndrome (ACS). Whenever possible, data are presented from randomized controlled trials (RCTs) and meta-analyses. Although guidelines recommend use of dual antiplatelet therapy (DAPT) after CABG for patients with ACS, available evidence is limited to small RCTs, and meta-analyses are of substudies of larger RCTs. There is also considerable heterogeneity in patient population of these studies; a significant number of patients underwent off-pump CABG (OPCAB) in trials that demonstrate graft-patency benefit with DAPT. With this limited evidence, DAPT remains underused in the CABG population, even among patients presenting after ACS.     

Antiplatelet Therapy and Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome and Thrombocytopenia

Platelets are crucial in the pathogenesis of acute coronary syndrome. Treatment for acute coronary syndrome usually involves antiplatelet, anticoagulant, and antithrombotic therapy, and the performance of percutaneous coronary intervention. All of the medications are associated with bleeding sequelae and are typically withheld from patients who have thrombocytopenia. The safety of antiplatelet therapy and percutaneous coronary intervention in patients who have acute coronary syndrome and thrombocytopenia is unknown, and there are no guidelines or randomized studies to suggest a treatment approach in such patients.Acute coronary syndrome is uncommon in patients who have thrombocytopenia; however, it occurs in up to 39% of patients who have both thrombocytopenia and cancer. Herein, we present the cases of 5 patients with acute coronary syndrome, thrombocytopenia, and cancer who underwent percutaneous coronary intervention with stenting. Before intervention, their platelet counts ranged from 17 to 72 × 10⁹/L. One patient underwent preprocedural platelet transfusion. All were given aspirin, alone or with clopidogrel. One patient experienced melena (of colonic origin). No other patient experienced bleeding sequelae.Aside from the occasional use of antiplatelet and thrombolytic agents in patients with thrombocytopenia, no therapeutic recommendation can be made until data are available on a larger patient population. Until then, treatment should conform to specific clinical circumstances. Approaches to the treatment of acute coronary syndrome in patients with thrombocytopenia might be better directed toward the evaluation of platelet function rather than toward absolute platelet count, and the risk–benefit equation of invasive procedures and antithrombotic therapies may need to incorporate this information.Key words: Angioplasty, transluminal, percutaneous coronary; anticoagulants/adverse effects; aspirin/therapeutic use; blood platelets/drug effects/physiology; coronary artery disease/physiopathology/prevention & control; hemorrhage/complications; myocardial infarction/drug therapy; neoplasms/complications; platelet aggregation inhibitors/administration & dosage/therapeutic use; platelet count/drug effects; thrombocytopenia/complications/drug therapy/etiology/prevention & controlPlatelets play a crucial role in the pathogenesis of acute coronary syndrome (ACS).¹ Although ACS in patients with thrombocytopenia is uncommon, it is found in up to 39% of patients who have both thrombocytopenia and cancer.² The standard treatment for ACS involves therapy with antiplatelet, anticoagulant, and thrombolytic agents, and the performance of percutaneous coronary intervention (PCI). All of these medications are associated with bleeding sequelae and are typically withheld from patients who have thrombocytopenia. The safety of antiplatelet therapy and PCI in patients who have ACS and thrombocytopenia is unknown, and there are no guidelines or randomized studies to suggest treatment approaches in such patients.Herein, we present a case series of patients with ACS, thrombocytopenia, and cancer who underwent PCI with stenting, and we discuss the treatment options.

Patient 1

A 60-year-old woman with multiple myeloma and a history of coronary artery disease presented at the hospital with chest pain and dyspnea. Her heart rate was 120 beats/min, and her blood pressure was 154/64 mmHg. Auscultation revealed a systolic ejection murmur and crackles in the left lung base. A 12-lead electrocardiogram (ECG) showed sinus tachycardia. Laboratory results included a platelet count of 21 ×10⁹/L, a hemoglobin level of 8.1 g/dL, a creatinine level of 0.8 mg/dL, and normal levels of cardiac enzymes. A transthoracic echocardiogram (TTE) showed normal left ventricular (LV) function and an ejection fraction (LVEF) of 0.60. The diagnosis of unstable angina was made, and she was treated with nitrates, aspirin, β-blockers, and a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor. After a coronary angiogram showed an 80% stenosis of the 1st diagonal branch of the left anterior descending coronary artery (LAD), PCI with stenting was performed, with no bleeding sequelae. Before the procedure, she was given a transfusion of 20 units of platelets. During the procedure, she was given 11,500 units of intravenous heparin, 200 μg of intracoronary nitroglycerin, and 300 mg of oral clopidogrel. The activating clotting time (ACT) recorded during the procedure was 190 sec. No platelet count was obtained after the procedure. The patient was discharged from the hospital and died of sepsis 4 years later.

Patient 2

A 70-year-old man with a history of coronary artery disease, diabetes mellitus, and acute myeloid leukemia presented at the hospital with chest pain and palpitations. His heart rate was 90 beats/min, and his blood pressure was 152/72 mmHg. A 12-lead ECG showed sinus rhythm and LV hypertrophy. Laboratory results included a platelet count of 46 ×10⁹/L, a hemoglobin level of 8.6 g/dL, and normal levels of cardiac enzymes. A TTE showed normal LV systolic function and an LVEF of 0.60. The diagnosis of unstable angina was made. Coronary angiography showed a 50% stenosis of the proximal circumflex artery, 95% stenosis of the distal circumflex artery, 75% stenosis of the proximal 1st obtuse marginal branch, and 100% occlusion of the proximal right coronary artery (RCA). During PCI, he received 7,500 units of intra-arterial heparin, 200 μg of intracoronary nitroglycerin, and 300 mg of oral clopidogrel. The maximum ACT recorded during the procedure was 238 sec. The patient underwent PCI and stenting of the circumflex artery, and he was given clopidogrel and aspirin for a month. However, he experienced chronic recurrent melena after PCI, and the aspirin and clopidogrel were temporarily discontinued. An upper gastrointestinal endoscopy and a colonoscopy showed colonic polyps, diverticulosis, and hemorrhoids, but no active bleeding. Chemotherapy was initiated a few days after the coronary revascularization, and the patient was discharged from the hospital.

Patient 3

A 69-year-old man with a history of diabetes mellitus, hypertension, and mantle-cell lymphoma presented at the hospital with recurrent episodes of chest pain. On examination, his heart rate was 60 beats/min, and his blood pressure was 130/70 mmHg. Splenomegaly was detected. A 12-lead ECG showed sinus rhythm. A TTE showed normal LV systolic function and an LVEF of 0.58. Laboratory results included a platelet count of 28 ×10⁹/L, a hemoglobin level of 11.1 g/dL, a creatinine level of 0.9 mg/dL, and an elevated troponin I level. The diagnosis of ACS was made, and the patient was given aspirin and clopidogrel. Coronary angiography revealed an 80% stenosis of the RCA, for which the patient underwent PCI with stent placement. During the procedure, he was given 8,500 units of intra-arterial heparin, 300 μg of intracoronary nitroglycerin, and 300 mg of oral clopidogrel. The maximum ACT during the procedure was 358 sec. He continued to take aspirin and clopidogrel without bleeding sequelae, and he experienced no further coronary events. He died of pneumonia 3 years later.

Patient 4

A 75-year-old man with a history of hypertension, diabetes mellitus, hypercholesterolemia, coronary artery bypass grafting (CABG), and chronic myeloid leukemia presented at the hospital with chest pain. His heart rate was 72 beats/min, and his blood pressure was 98/40 mmHg. A 12-lead ECG showed a 1-mm ST elevation in the inferior leads, a 1-mm ST depression in leads I and aVL, and a right bundle branch block. Laboratory results included a platelet count of 72 ×10⁹/L, a hemoglobin level of 8.5 g/dL, a creatinine level of 1.2 mg/dL, and normal levels of cardiac enzymes. A TTE showed an LVEF of 0.45. The diagnosis of ACS was made, and the patient was started on aspirin, clopidogrel, and nitroglycerin. Coronary angiography showed a 60% to 70% stenosis of the native circumflex artery, 100% occlusion of the native LAD, and 99% stenosis at the anastomosis site of the saphenous vein graft (SVG) to the LAD. The patient underwent PCI with stent placement at the anastomosis site and experienced no bleeding sequelae. During the procedure, he was given 6,000 units of heparin intravenously, an intravenous integrilin bolus of 12.4 mg followed by an integrilin infusion at a dose of 2.037 μg/kg/min, oral clopidogrel of 150 mg, and (by injection into the LAD graft) 200 μg of nitroglycerin and 100 μg of adenosine. The recorded ACT during the procedure was 206 sec. He died 1 month later of sepsis.

Patient 5

An 80-year-old man with a history of hypertension, hypercholesterolemia, and acute myeloid leukemia presented at the hospital with chest pain. His heart rate was 65 beats/min, and his blood pressure was 120/62 mmHg. A 12-lead ECG showed atrial fibrillation with a left bundle branch block. Laboratory results included a platelet count of 17 ×10⁹/L, a hemoglobin level of 8.3 g/dL, a creatinine level of 1.2 mg/dL, and an elevated troponin I level with a peak value of 11.91 ng/mL (normal value, <0.4 ng/mL). A TTE showed normal LV systolic function and an LVEF of 0.54. The diagnosis of ACS was made, and the patient was treated with aspirin, nitroglycerin, and β-blockers. Coronary angiography showed a 90% lesion in the obtuse marginal branch of the circumflex coronary artery and a 40% to 50% stenosis of the distal RCA. The patient underwent PCI without stent placement in the obtuse marginal branch and experienced no bleeding sequelae. During the procedure, he was given 5,000 units of intravenous heparin, 400 μg of intracoronary nitroglycerin, and 325 mg of oral aspirin. The ACT recorded during the procedure was 262 sec. Seven days after PCI, he experienced an episode of noncardiac chest pain, after completion of a platelet transfusion. One week later, a temporary pacemaker was inserted because of severe bradycardia. His general condition deteriorated, and he died 22 days after PCI of multiorgan failure, pneumonia, and diffuse alveolar hemorrhage.Figure 1 shows the available pre- and post-PCI platelet counts.TABLE I. Clinical Presentation and Treatment of the Patients with Acute Coronary Syndrome and ThrombocytopeniaOpen in a separate windowOpen in a separate windowFig. 1 Platelet counts before and after percutaneous coronary intervention (PCI). No post-PCI platelet count was obtained in patient 1. In the other 4 patients, the post-PCI platelet counts were obtained from 24 hours to 20 days after PCI.     

Spontaneous Chest Wall Hematoma With Dual Antiplatelet Therapy

Spontaneous chest wall hematoma is rare and has been associated with neoplasms and arteriovenous malformations. However, the increasing use of anticoagulant and antiplatelet agents has increased the clinical presentation of spontaneous hematomas. Clopidrogel and aspirin are antiplatelet agents widely used in the treatment of peripheral vascular, cerebrovascular, and coronary artery disease. Although bleeding is a known adverse effect, only a small number of cases of hematomas associated with antiplatelet agents have been described. We report a case of a large spontaneous latissimus dorsi hematoma in a patient receiving clopidogrel and aspirin therapy.