Marc P Bonaca

Brigham and Women's Hospital | BWH · Division of Cardiovascular Medicine

Background: The ability of polygenic risk scores (PRS) to predict heart failure (HF) beyond classic risk factors is unclear. Aims: To evaluate the risk of a HF PRS with incident hospitalization for HF (HHF) in patients with established cardiovascular disease. Methods: We analyzed a 59 SNP HF PRS (HERMES collaboration, Henry et al) in genotyped pati...

Introduction: Patients with diabetes are at higher risk of chronic limb-threatening ischemia (CLTI), a severe form of peripheral artery disease (PAD) causing restricted blood flow to the lower limbs due, in part, to impaired angiogenesis. However, the role of microRNAs (miRNAs) in diabetic CLTI remains poorly understood. By integrating plasma miRNA...

Aims: To comprehensively evaluate the safety of dapagliflozin in patients with type 2 diabetes (T2DM) with emphasis placed on potential safety concerns related to the SGLT2-inhibitors class. Methods: In DECLARE-TIMI 58, 17,160 patients with T2DM were randomized to dapagliflozin or placebo and followed for a median of 4.2 years. Safety was evalua...

Background: The relationship between cholesterol levels and risk of venous thromboembolism (VTE) is uncertain. We set out to determine the effect of PCSK9 inhibition on the risk of VTE, explore potential mechanisms, and examine the efficacy in clinically and genetically defined risk subgroups. Methods: We performed a post-hoc analysis of the FOURIE...

Background: The PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). We investigated the efficacy and safety of evolocumab in patients with...

Background: Observational studies suggest that symptomatic atherosclerosis may be associated with risk of venous thromboembolism (VTE). Prior randomized studies have demonstrated a significant reduction in recurrent VTE with aspirin monotherapy. Whether VTE risk is associated with more severe symptomatic atherosclerosis and more intensive antiplat...

Background: Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time. Objectives: The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and saf...

Background: In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. Objectives: The authors evaluated cost-effectiveness of ticagrelor + low-...

Diabetes increases cardiovascular risk and reduces pharmacodynamic response to some oral antiplatelet drugs. This study aimed to determine whether ticagrelor 60 mg twice daily (bid) provided potent and consistent platelet inhibition in patients with vs without diabetes in the PEGASUS-TIMI 54 platelet function substudy. Out of 180 patients studied,...

Background: Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain. Objectives: The study investigated the efficacy and safety of the potent P2Y12 inhibitors in patients with coronary artery disease. Method...

Introduction: Adiponectin is a pleiotropic adipocytokine with a strong inverse (protective) association with obesity, diabetes, and cardiovascular outcomes in stable patients. However, this relationship may be reversed in the setting of acute coronary syndrome (ACS). Given this possible complex relationship, we investigated adiponectin and cardiov...

Patients with prior myocardial infarction (MI) are at long-term heightened risk for recurrent ischemic events. Several large randomized controlled trials have demonstrated the benefit of more intensive antiplatelet strategies for long-term secondary prevention of cardiovascular death, recurrent MI, and stroke in patients with a history of MI at a c...

Article, see p 1603 Head-to-head comparison of currently available therapies remains a significant challenge. As newer generation agents are developed, they are each compared against the prior standard of care to prove either superiority or noninferiority; however, they are rarely compared against each other. Cross-trial comparisons of efficacy a...

Objectives: The aim of this study was to determine whether the reduction in peripheral revascularization with vorapaxar in patients with peripheral artery disease (PAD) is directionally consistent across indications, including acute limb ischemia, progressively disabling symptoms, or both. Background: The protease-activated receptor-1 antagonist...

Background: In the PEGASUS-TIMI 54 trial (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), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior...

Background: -Patients with stable ischemic heart disease and prior MI vary in their risk for recurrent CV events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential for benefit from more intensive secondary preventative therapy such as treatment with vorapaxar. Methods: -We identified in...

Background Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first‐in‐class platelet protease‐activated receptor ‐1 antagonist, on new or recurrent MI. Met...

BACKGROUND Patients with diabetes appear to be at elevated risk of atherothrombotic events. OBJECTIVES The purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI). METHODS We examined the subgroups of patients with diabetes...

Background A prior randomized controlled trial of social media exposure at Circulation determined that social media did not increase 30‐day page views. Whether insufficient social media intensity contributed to these results is uncertain. Methods and Results Original article manuscripts were randomized to social media exposure compared with no soc...

Background: Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for the reduction of cardiovascular death, myocardial infarction, and stroke in stable patients with prior atherothrombosis, who have not had a prior stroke or transient ischemic attack. The aims of this study were to investigate: 1) the role of vorapaxar...

Importance: p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes. Obj...

Background: Diabetic patients appear to be at elevated risk of atherothrombotic events. Objectives: To determine the impact of antiplatelet therapy with ticagrelor on recurrent ischemic events in diabetic patients with prior myocardial infarction (MI). Methods: We examined the subgroups of patients with diabetes (N= 6806) and without diabetes...

Background: Peripheral artery disease (PAD) has been associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). Objective: s: In PEGASUS-TIMI 54, a trial of patients with prior MI, we evaluated the efficacy and safety of ticagrelor on major cardiovascular and major adverse limb events in PAD patients...

Background: 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 studied 2 doses of ticagrelor, 90 mg twice a day (bid) and 60 mg bid, for long-term prevention of ischemic events in patients with p...

Background: -Patients with peripheral artery disease (PAD), are at heightened risk of acute limb ischemia (ALI), a morbid event that may result in limb loss. We investigated the causes, sequelae and predictors of ALI in a contemporary population with symptomatic PAD and whether PAR-1 antagonism with vorapaxar reduced ALI overall and by etiology....

Vorapaxar is a first-in-class PAR-1 antagonist indicated for secondary prevention in stable patients with prior myocardial infarction (MI) or peripheral artery disease and no cerebrovascular disease. Vorapaxar is not recommended for initiation in the acute phase of acute coronary syndromes (ACS) because of an unfavorable balance between bleeding an...

Aims Ticagrelor reduced major adverse cardiovascular event (MACE) by 15–16% in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y12 inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of ther...

Aims: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). Methods and results: Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGF...

-Vorapaxar antagonizes protease-activated receptor (PAR)-1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a prior myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine...

Aims: Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations,with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascularmortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with...

Despite treatments for secondary prevention, patients with prior myocardial infarction (MI) remain at high risk for recurrent thrombotic events.1 The addition of a P2Y12 receptor antagonist to aspirin for the first year after an acute coronary syndrome (ACS) has been shown to reduce the risk of cardiovascular (CV) death, MI, or stroke.2–4 Based on...

Abstract BACKGROUND The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y(12) receptor antagonist with established efficacy after an acute coronary syndrome, in this context. METHODS We randomly assigned, in a double...

Patients with peripheral artery disease (PAD) are at heightened risk of both systemic cardiovascular adverse events, as well as limb-related morbidity. The optimal management of patients with PAD requires a comprehensive treatment strategy incorporating both lifestyle changes, including smoking cessation and exercise, as well as optimal medical the...

Background: The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context. Methods: We randomly assigned, in a double-blind 1:1:1...

High-sensitivity cardiac troponin T (hsTnT) is used in many countries, but is not available in the United States. Prior evidence has been viewed as inconclusive as to whether low cardiac troponin T (cTnT) concentrations detected with hsTnT are prognostically meaningful compared with fourth-generation cTnT. The aim of this study was to assess the pr...

Vorapaxar is a protease-activated receptor-1 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA). We examined the efficac...

-Vorapaxar reduces cardiovascular death (CVD), myocardial infarction (MI), or stroke in patients with prior MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. TRA 2°P-TIMI 50 was a randomized, dou...

Background: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined. Methods: We measured hs-TnI (Abbott ARCHITECT) in 15833 pat...

Newer troponin assays offer the ability to quantify circulating troponin levels at an order of magnitude lower than contemporary assays, fueling continued debate over the prognostic implications of very low-level increases in concentration. We evaluated the prognostic implications of low-level increases in cardiac troponin I (cTnI) using an investi...

Vorapaxar, a novel thrombin receptor antagonist, reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy in patients with stable atherosclerotic vascular disease. The goal of this study was to test the hypothesis that treatment with vorapaxar reduces the rate of coronary stent thrombosis (ST) in stab...

Background: Vorapaxar, a novel antiplatelet therapy, reduces thrombotic events in patients with a history of myocardial infarction (MI) or peripheral artery disease (PAD); however, because of an increased risk of intracranial hemorrhage, it is contraindicated in patients with a history of stroke. Objectives: The aim of this study was to investig...

Vorapaxar is a potent platelet inhibitor that reduces thrombotic events in stable patients with a history of myocardial infarction (MI) or peripheral artery disease (PAD); however, this benefit is offset by increased bleeding including intracranial hemorrhage particularly in patients with established cerebrovascular disease (CVD). We investigated t...

-Medical journals use social media to distribute the findings of published articles. Whether social media exposure to original articles improves article impact metrics is uncertain. -Articles were randomized to receive targeted social media exposure from Circulation, including postings on the journal's Facebook and Twitter feeds. The primary end-po...

Acute aortic syndromes constitute a spectrum of conditions characterized by disruptions in the integrity of the aortic wall that may lead to potentially catastrophic outcomes. They include classic aortic dissection, intramural hematoma, and penetrating aortic ulcer. Although imaging studies are sensitive and specific, timely diagnosis can be delaye...

Importance Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2 enzyme.Objective To evaluate the efficacy and safety of darapladib in patients after an acute coronary syndrome (ACS) event.Design, S...

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular events following acute coronary syndrome (ACS). The underlying pathobiology and optimal treatments for this population continue to be evaluated. Patients with CKD will receive fewer evidence-based therapies and experience high rates of adverse cardiovascular events...

The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) is not known. Factors influencing DAPT duration are not well described. We hypothesized that continued DAPT 12 months beyond ACS would be associated with patient factors such as stent type and that it may be associated with lower rates of ischemic events. T...

Objective To assess the prognostic performance of C-terminal provasopressin (copeptin), midregional-pro-adrenomedullin (MR-proADM), and midregional-pro-atrial natriuretic peptide (MR-proANP) in a large prospective cohort of patients with NSTE-ACS. Background Copeptin, MR-proADM, and MR-proANP are emerging biomarkers of hemodynamic stress that have...

Arginine-vasopressin (AVP) is an acute marker of physiologic stress. Copeptin is the C-terminal fragment of vasopressin precursor hormone that is more easily measured than AVP. Studies assessing the utility of copeptin in the diagnosis of myocardial infarction (MI) have demonstrated mixed results. The aim of this study was to test the hypothesis th...

P2Y12 receptor antagonist therapy is recommended in addition to ASA for up to 1 year after acute coronary syndrome to reduce ischemic events. In contrast, the benefit of long-term dual antiplatelet therapy beyond 1 year remains unclear. Ticagrelor is a potent, reversibly binding P2Y12 receptor-antagonist that has been shown to be superior to clopid...

Asymptomatic carotid-artery atherosclerotic vascular disease identifies patients at heightened risk of major adverse cardiovascular events including ischemic stroke. Observational and registry analyses demonstrate that this risk extends beyond that attributable to carotid atherosclerosis itself and includes events manifesting in other vascular terr...

Cardiovascular disease is the leading cause of death worldwide. Acute aortic syndromes, which include aortic dissection, intramural hematoma, and penetrating aortic ulcer, represent the most morbid presentations of aortic disease and can be difficult to diagnose. Recent advances in imaging have allowed for more rapid and accurate diagnosis of acute...

Ticagrelor is a potent P2Y12 adenosine diphosphate receptor antagonist characterized by a rapid onset, consistent and reversible antiplatelet effect, and an acceptable safety profile compared with existing adenosine diphosphate receptor blockers. In the large Phase III trial, PLATO, ticagrelor significantly reduced the composite of cardiovascular d...

Background: High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. Methods: We evaluated the prognostic performance of a new high-sensitivity cardiac tro...

Background: Rapid diagnosis of acute coronary syndrome is a clinical and operational priority in busy emergency departments (ED). We examined the performance of an investigational troponin I (TnI) assay with 10-100-times greater sensitivity than current commercial assays. Methods: Among patients with non-traumatic chest pain enrolled in the BWH-...

Improvement in analytical performance over successive generations of assays for cardiac troponin (cTn) has enabled detection of progressively lower concentrations with acceptable precision. By expert convention [(1)][1], assays designated as “high-sensitivity” (hs) detect circulating cTn in

Opinion statement: Patients with atherosclerotic asymptomatic carotid artery disease are at a heightened risk of major adverse cardiovascular events including ischemic stroke. Intensive risk factor modification, including lifestyle interventions and the use of evidence based medical therapies, reduces the risk of adverse cardiovascular events in t...

Background: Vorapaxar is a novel antagonist of protease-activated receptor-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with peripheral artery disease are at risk of systemic atherothrombotic events, as well as acute and chronic limb ischemia and the need for perip...

Background and purpose: Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the protease-activated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. Methods: We randomly assigned pat...

Vorapaxar is an antiplatelet agent that potently inhibits thrombin-mediated activation of the platelet protease-activated receptor (PAR)-1. Phase 2 trials of vorapaxar suggested efficacy with acceptable safety in patients with ischemic stroke. Methods: TRA 2°P–TIMI 50 was a multinational, randomized, double-blinded, placebo-controlled trial of 2644...

Chest pain is one of the most common reasons for presentation to the Emergency Department and the ability to rapidly and correctly diagnose the minority of patients who have a myocardial infarction is of critical importance. We assessed the diagnostic performance of a multimarker strategy using heart-type fatty acid binding protein (H-FABP) in comb...