Publications by authors named "Gregory Piazza"

137 Publications

Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: The PREVENT-HD study.

Am Heart J 2021 Feb 9;235:12-23. Epub 2021 Feb 9.

CPC Clinical Research, Aurora, CO; Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.

Background: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established.

Study Design: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events.

Conclusions: PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.
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http://dx.doi.org/10.1016/j.ahj.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871775PMC
February 2021

Association of ABO blood group type with cardiovascular events in COVID-19.

J Thromb Thrombolysis 2021 Jan 15. Epub 2021 Jan 15.

Division of Cardiovascular Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, 75 Francis St., Boston, MA, 02115, USA.

Cardiovascular complications have been reported in patients with COVID-19. We sought to examine the association of ABO blood group type with cardiovascular complications in COVID-19. We examined 409 individuals enrolled in the COVID-19 Registry to Assess Frequency, Management, and Outcomes of Arterial and Venous Thromboembolic Complications (CORONA-VTE) who had ABO blood group data available. Multiple logistic regression was used to assess the association of ABO blood group types with three primary outcomes: major adverse cardiovascular events (MACE), major arterial and venous thrombosis and all-cause mortality. 201, 121, 61 and 26 individuals had blood group O, A, B and AB, respectively. In multivariable analysis, blood group A was associated with a 2.5-fold higher odds of MACE than blood group O (OR 2.47[1.18-5.18]). There was an effect suggesting a 2-fold higher odds of major thrombotic events in blood group A vs. O that did not reach statistical significance (OR 2.15 [0.89-5.20]). No association between blood group type and all-cause mortality was found. Compared with the other blood group types, blood group A was associated with an increased odds of MACE(OR 2.18[1.11-4.29]), while blood group O was associated with lower odds of MACE(OR 0.50[0.26-0.97]). In conclusion, blood group A was associated with an increased odds of MACE, whereas blood group O was associated with a reduction in the odds of MACE in patients with COVID-19. These findings may inform risk stratification of COVID-19 patients for cardiovascular complications. Additional studies are needed to validate our findings.
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http://dx.doi.org/10.1007/s11239-020-02364-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810281PMC
January 2021

First-in-Human Study to Assess the Safety and Feasibility of the Bashir Endovascular Catheter for the Treatment of Acute Intermediate-Risk Pulmonary Embolism.

Circ Cardiovasc Interv 2021 Jan 24;14(1):e009611. Epub 2020 Dec 24.

Department of Cardiology, Massachusetts General Hospital, Boston, MA (K.R.).

Background: The Bashir Endovascular Catheter (BEC) is a novel pharmaco-mechanical device designed to enhance thrombolysis by increasing the exposure of thrombus to endogenous and exogenous thrombolytics. The aim of this prospective, multicenter, single-arm study was to evaluate the feasibility and initial safety of the BEC in patients with acute intermediate-risk pulmonary embolism (PE).

Methods: Patients with symptomatic PE and right ventricular to left ventricular diameter ratio ≥0.9 as documented by computer tomography angiography were eligible for enrollment. The primary safety end points were device related death or adverse events, and major bleeding within 72 hours after BEC directed therapy.

Results: Nine patients were enrolled across 4 US sites. The total dose of r-tPA (recombinant tissue-type plasminogen activator) was 14 mgs in bilateral PE and 12 mgs in unilateral PE over 8 hours delivered via the expanded BEC. At 30-day follow-up, there were no deaths or device-related adverse events. At 48 hours post-BEC therapy, the right ventricular to left ventricular diameter ratio decreased from 1.52±0.26 to 0.97±0.06 (=0.0009 [95% CI, 0.33-0.82]; 37.0% reduction). Thrombus burden as measured by the Modified Miller Index decreased from 25.4±5.3 to 16.0±4.0 (=0.0005; [95% CI, 5.5-13.4]; 37.1% reduction).

Conclusions: In this early feasibility study of the BEC for intermediate-risk PE, there were no deaths or device-related adverse events and a significant reduction in right ventricular to left ventricular diameter ratio and thrombus burden. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03927508.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009611DOI Listing
January 2021

Update on Guidelines for the Management of Cancer-Associated Thrombosis.

Oncologist 2021 Jan 4;26(1):e24-e40. Epub 2020 Dec 4.

Harvard Medical School, Boston, Massachusetts, USA.

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with cancer. Over the past 2 decades, enormous advances have been made in the management of CAT. The growing evidence base informing practice has led to the publication of a number of guidelines and guidance documents on the diagnosis and treatment of CAT. The goal of this review is to examine the latest versions of evidence-based guidelines, highlighting the differences and similarities in their methodology, their disease-specific content, and recommendations for management. Our analysis shows that for most clinical topics, the different guidelines provide roughly similar management advice. However, there are a number of important clinical topics in CAT that are not currently covered by the existing guidelines. We think inclusion of these topics in future versions of the guidelines will facilitate ongoing efforts to optimize the care of patients with CAT. IMPLICATIONS FOR PRACTICE: Cancer-associated thrombosis (CAT) is a common complication in patients with cancer. This review examines the differences and similarities of the current CAT guidelines methods and recommendations. Current guidelines largely agree on many aspects of CAT management. However, there are a number of topics in CAT that are not currently included in guidelines where evidence-based guidance would be very helpful for clinicians. Coverage of these topics in future guidelines is encouraged to optimize clinical practice.
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http://dx.doi.org/10.1002/onco.13596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794170PMC
January 2021

Diagnosis, Management, and Pathophysiology of Arterial and Venous Thrombosis in COVID-19.

JAMA 2020 Dec;324(24):2548-2549

Critical Care Cardiology, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jama.2020.23422DOI Listing
December 2020

Identification and Outcomes of Hospitalized Medically Ill Patients Who Are Candidates for Extended Duration Thromboprophylaxis.

TH Open 2020 Oct 31;4(4):e344-e350. Epub 2020 Oct 31.

Institute for Health Innovations and Outcomes Research, Feinstein Institutes for Medical Research and the Zucker School of Medicine at Hofstra/Northwell, New York, New York, United States.

 Extended duration thromboprophylaxis (ET) for approximately 30 days can effectively and safely reduce venous thromboembolism (VTE) risk in appropriately selected medically ill patients. We sought to estimate the proportion of hospitalized medically ill patients potentially qualifying for ET and assess their post-discharge clinical and economic outcomes using a large claims database.  Using MarketScan claims from January 2012 to September 2018, we identified medically ill patients hospitalized with a primary diagnosis of heart failure, respiratory insufficiency, ischemic stroke, infection, or inflammatory disease and ≥1-additional risk factor for VTE. Patients < 40 years old, a length-of-stay < 3 or >30 days, receiving oral anticoagulation prior to index hospitalization or having an indication for full-dose anticoagulation were excluded, as were patients deemed high-risk for bleeding due to active, in-hospital treated cancer, gastroduodenal ulcer or bleeding within the prior 3 months, bronchiectasis, pulmonary cavitation or hemorrhage, or dual antiplatelet therapy use.  We identified 2,782,988 patients ≥40 years of age and admitted for a high-risk medical illness. Of these, 724,531 patients (26.0%) were identified as ET candidates. Patients' VTE risk appeared highest in the first 30 days post-discharge (1,532/724,531, 0.2%). Adjusted post-index hospitalization costs (2018 US$) for patients with a VTE within 30 days were higher than those without VTE (Δ = $32,623 at 30 days, Δ = $43,325 at 90 days, Δ = $53,668 at 365 days;  < 0.001 for all).  Post-discharge VTE in high-risk patients with medical illness is associated with substantially increased costs.
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http://dx.doi.org/10.1055/s-0040-1718911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603421PMC
October 2020

Diagnosis and Treatment of Lower Extremity Venous Thromboembolism: A Review.

JAMA 2020 Nov;324(17):1765-1776

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event.

Observations: PubMed and Cochrane databases were searched for English-language studies published from January 2015 through June 2020 for randomized clinical trials, meta-analyses, systematic reviews, and observational studies. Risk factors for venous thromboembolism (VTE), such as older age, malignancy (cumulative incidence of 7.4% after a median of 19 months), inflammatory disorders (VTE risk is 4.7% in patients with rheumatoid arthritis and 2.5% in those without), and inherited thrombophilia (factor V Leiden carriers with a 10-year cumulative incidence of 10.9%), are associated with higher risk of VTE. Patients with signs or symptoms of lower extremity DVT, such as swelling (71%) or a cramping or pulling discomfort in the thigh or calf (53%), should undergo assessment of pretest probability followed by D-dimer testing and imaging with venous ultrasonography. A normal D-dimer level (ie, D-dimer <500 ng/mL) excludes acute VTE when combined with a low pretest probability (ie, Wells DVT score ≤1). In patients with a high pretest probability, the negative predictive value of a D-dimer less than 500 ng/mL is 92%. Consequently, D-dimer cannot be used to exclude DVT without an assessment of pretest probability. Postthrombotic syndrome, defined as persistent symptoms, signs of chronic venous insufficiency, or both, occurs in 25% to 50% of patients 3 to 6 months after DVT diagnosis. Catheter-directed fibrinolysis with or without mechanical thrombectomy is appropriate in those with iliofemoral obstruction, severe symptoms, and a low risk of bleeding. The efficacy of direct oral anticoagulants-rivaroxaban, apixaban, dabigatran, and edoxaban-is noninferior to warfarin (absolute rate of recurrent VTE or VTE-related death, 2.0% vs 2.2%). Major bleeding occurs in 1.1% of patients treated with direct oral anticoagulants vs 1.8% treated with warfarin.

Conclusions And Relevance: Greater recognition of VTE risk factors and advances in anticoagulation have facilitated the clinical evaluation and treatment of patients with DVT. Direct oral anticoagulants are noninferior to warfarin with regard to efficacy and are associated with lower rates of bleeding, but costs limit use for some patients.
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http://dx.doi.org/10.1001/jama.2020.17272DOI Listing
November 2020

Advanced Management of Intermediate- and High-Risk Pulmonary Embolism: JACC Focus Seminar.

Authors:
Gregory Piazza

J Am Coll Cardiol 2020 11;76(18):2117-2127

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Intermediate-risk (submassive) pulmonary embolism (PE) describes normotensive patients with evidence of right ventricular compromise, whereas high-risk (massive) PE comprises those who have experienced hemodynamic decompensation with hypotension, cardiogenic shock, or cardiac arrest. Together, these 2 syndromes represent the most clinically challenging manifestations of the PE spectrum. Prompt therapeutic anticoagulation remains the cornerstone of therapy for both intermediate- and high-risk PE. Patients with intermediate-risk PE who subsequently deteriorate despite anticoagulation and those with high-risk PE require additional advanced therapies, typically focused on pulmonary artery reperfusion. Strategies for reperfusion therapy include systemic fibrinolysis, surgical pulmonary embolectomy, and a growing number of options for catheter-based therapy. Multidisciplinary PE response teams can aid in selection of appropriate management strategies, especially where gaps in evidence exist and guideline recommendations are sparse.
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http://dx.doi.org/10.1016/j.jacc.2020.05.028DOI Listing
November 2020

Registry of Arterial and Venous Thromboembolic Complications in Patients With COVID-19.

J Am Coll Cardiol 2020 11;76(18):2060-2072

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Cardiovascular complications, including myocardial infarction, ischemic stroke, and pulmonary embolism, represent an important source of adverse outcomes in coronavirus disease-2019 (COVID-19).

Objectives: To assess the frequency of arterial and venous thromboembolic disease, risk factors, prevention and management patterns, and outcomes in patients with COVID-19, the authors designed a multicenter, observational cohort study.

Methods: We analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through our Mass General Brigham integrated health network. The total cohort was analyzed by site of care: intensive care (n = 170); hospitalized nonintensive care (n = 229); and outpatient (n = 715). The primary study outcome was a composite of adjudicated major arterial or venous thromboembolism.

Results: Patients with COVID-19 were 22.3% Hispanic/Latinx and 44.2% non-White. Cardiovascular risk factors of hypertension (35.8%), hyperlipidemia (28.6%), and diabetes (18.0%) were common. Prophylactic anticoagulation was prescribed in 89.4% of patients with COVID-19 in the intensive care cohort and 84.7% of those in the hospitalized nonintensive care setting. Frequencies of major arterial or venous thromboembolism, major cardiovascular adverse events, and symptomatic venous thromboembolism were highest in the intensive care cohort (35.3%, 45.9%, and 27.0 %, respectively) followed by the hospitalized nonintensive care cohort (2.6%, 6.1%, and 2.2%, respectively) and the outpatient cohort (0% for all).

Conclusions: Major arterial or venous thromboembolism, major adverse cardiovascular events, and symptomatic venous thromboembolism occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high utilization rate of thromboprophylaxis.
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http://dx.doi.org/10.1016/j.jacc.2020.08.070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588178PMC
November 2020

Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials.

Semin Thromb Hemost 2020 Nov 21;46(8):908-918. Epub 2020 Oct 21.

Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.

Thrombotic cardiovascular disease (myocardial infarction [MI], stroke, and venous thromboembolism [VTE]) remains a major cause of death and disability. Sulodexide is an oral glycosaminoglycan containing heparan sulfate and dermatan sulfate. We conducted a systematic review and meta-analysis to determine the cardiovascular efficacy, and safety of sulodexide versus control in randomized controlled trials (RCTs). We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs reporting cardiovascular outcomes in patients receiving sulodexide versus control (placebo or no treatment). Outcomes included all-cause mortality, cardiovascular mortality, MI, stroke, deep vein thrombosis (DVT), pulmonary embolism, and bleeding. We used inverse variance random-effects models with odds ratio (OR) as the effect measure. After screening 360 records, 6 RCTs including 7,596 patients (median follow-up duration: 11.6 months) were included. Patients were enrolled for history of MI, VTE, peripheral arterial disease, or cardiovascular risk factors plus nephropathy. Use of sulodexide compared with control was associated with reduced odds of all-cause mortality (OR 0.67, 95% confidence interval [CI] 0.52-0.85,  = 0.001), cardiovascular mortality (OR 0.44, 95% CI 0.22-0.89,  = 0.02), and MI (OR 0.70, 95% CI 0.51-0.96,  = 0.03), and nonsignificantly reduced odds of stroke (OR 0.78, 95% CI 0.45-1.35,  = 0.38). Sulodexide was associated with significantly reduced odds of VTE (OR 0.44, 95% CI 0.24-0.81,  = 0.008), including DVT (OR 0.41, 95% CI 0.26-0.65,  < 0.001), but not pulmonary embolism (OR 0.92, 95% CI 0.40-2.15,  = 0.86). Bleeding events were not significantly different in the two groups (OR 1.14, 95% CI 0.47-2.74,  = 0.48). In six RCTs across a variety of clinical indications, use of sulodexide compared with placebo or no treatment was associated with reduced odds of all-cause mortality, cardiovascular mortality, MI, and DVT, without a significant increase in bleeding. Additional studies with this agent are warranted.
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http://dx.doi.org/10.1055/s-0040-1716874DOI Listing
November 2020

The Potential Role of Coagulation Factor Xa in the Pathophysiology of COVID-19: A Role for Anticoagulants as Multimodal Therapeutic Agents.

TH Open 2020 Oct 7;4(4):e288-e299. Epub 2020 Oct 7.

Division of Cardiovascular Medicine Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.

SARS-CoV-2 infection (COVID-19) results in local and systemic activation of inflammation and coagulation. In this review article, we will discuss the potential role of coagulation factor Xa (FXa) in the pathophysiology of COVID-19. FXa, a serine protease, has been shown to play a role in the cleavage of SARS-CoV-1 spike protein (SP), with the inhibition of FXa resulting in the inhibition of viral infectivity. FX is known to be primarily produced in the liver, but it is also expressed by multiple cells types, including alveolar epithelium, cardiac myocytes, and macrophages. Considering that patients with preexisting conditions, including cardiopulmonary disease, are at an increased risk of severe COVID-19, we discuss the potential role of increased levels of FX in these patients, resulting in a potential increased propensity to have a higher infectious rate and viral load, increased activation of coagulation and inflammation, and development of fibrosis. With these observations in mind, we postulate as to the potential therapeutic role of FXa inhibitors as a prophylactic and therapeutic treatment for high-risk patients with COVID-19.
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http://dx.doi.org/10.1055/s-0040-1718415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541169PMC
October 2020

Patients with perceived high-bleeding risk and computerized decision support for stroke prevention in atrial fibrillation: an AF-ALERT substudy : Piazza: outcomes of high-bleeding risk AF patients.

J Thromb Thrombolysis 2020 Sep 30. Epub 2020 Sep 30.

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

A perceived increased risk of bleeding is one of the most frequent reasons for withholding anticoagulation for stroke prevention in atrial fibrillation (AF). We previously conducted a randomized controlled trial of alert-based computerized decision support to increase prescription of anticoagulation in hospitalized patients with AF. To determine the clinical characteristics and outcomes of those patients whose inpatient health care providers received a computer alert, we analyzed all 248 patients in the alert group. Patients for whom providers elected to omit anticoagulation and provided a rationale of a perceived high risk of bleeding were compared with those who were not designated as high-risk. Perceived high risk of bleeding was the most common reason (77%) for omitting anticoagulation. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p = 0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation by 90 days. The frequency of major and clinically-relevant non-major bleeding was similar between the groups. The frequency of death, myocardial infarction, stroke, or systemic embolic event was similar in both groups (10.2% vs. 12.4%, p = 0.59). In conclusion, a perceived high risk of bleeding was the most common reason for omission of anticoagulation in patients with AF after a computerized alert. Perceived high risk of bleeding was not reflected in a higher HAS-BLED score.Clinical trial registration: ClinicalTrials.gov Identifier: NCT02339493 https://clinicaltrials.gov/ct2/show/NCT02339493 In a randomized controlled trial of computerized decision support to increase prescription of antithrombotic therapy in hospitalized patients with atrial fibrillation (AF), a perceived high risk of bleeding was the most common reason (77%) for omitting antithrombotic therapy after an on-screen alert. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p = 0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy for stroke prevention at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation over the ensuing 90 days.
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http://dx.doi.org/10.1007/s11239-020-02296-0DOI Listing
September 2020

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies.

Thromb Res 2020 12 24;196:382-394. Epub 2020 Sep 24.

Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Iran; Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Iran. Electronic address:

Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown.

Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts.

Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.
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http://dx.doi.org/10.1016/j.thromres.2020.09.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513771PMC
December 2020

Meta-Analysis Comparing Direct Oral Anticoagulants to Low Molecular Weight Heparin for Treatment of Venous Thromboembolism in Patients With Cancer.

Am J Cardiol 2020 10 25;133:175-178. Epub 2020 Jul 25.

Section of Vascular Medicine, NorthShore University Health System, University of Chicago, Evanston, Illinois; Leon H. Charney Division of Cardiology, New York University Grossman School of Medicine, New York, New York. Electronic address:

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http://dx.doi.org/10.1016/j.amjcard.2020.07.027DOI Listing
October 2020

One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism.

Circ Cardiovasc Interv 2020 08 6;13(8):e009012. Epub 2020 Aug 6.

Department of Cardiovascular and Interventional Radiology, INOVA Alexandria Hospital, VA (K.M.S.).

Background: Accelerated tPA (tissue-type plasminogen activator) dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis improve short-term computed tomographic-measured right ventricular (RV)-to-left ventricular diameter ratio in massive and submassive pulmonary embolism. The impact on RV remodeling, functional status, and quality of life over the long-term remains unclear.

Methods: To study 1-year changes in RV remodeling, functional status, and quality of life, we assessed patients with acute submassive pulmonary embolism randomly assigned to 1 of 4 tPA dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis in the OPTALYSE-PE trial (Optimum Duration and Dose of r-tPA With the Acoustic Pulse Thrombolysis Procedure for Intermediate-Risk Pulmonary Embolism; 8 mg/2 hours, 8 mg/4 hours, 12 mg/6 hours, and 24 mg/6 hours). Echocardiographic assessment included RV-to-left ventricular diameter ratio within 4 hours of treatment end, and at 48 hours, 30 days, 90 days, and 1 year. Functional status was assessed by 6-minute walk test at 30 days, 90 days, and 1 year and PROMIS-PF-6b scores at 30 days, 90 days, 180 days, 270 days, and 1 year. Quality of life was evaluated by PEmb-QOL scores at 30 days, 90 days, 180 days, 270 days, and 1 year.

Results: Mean RV-to-left ventricular diameter ratio decreased from baseline to 4 hours and further at 48 hours and 30 days, with reductions maintained at 90 days and 1 year in all groups. Mean 6-minute walk distance, PROMIS-PF-6b, and PEmb-QOL scores improved over the course of 1 year in all groups.

Conclusions: Accelerated lower-dose tPA regimens for ultrasound-facilitated, catheter-directed fibrinolysis resulted in sustained recovery of RV-to-left ventricular diameter ratio and tricuspid annular plane systolic excursion and improvements in functional status and quality of life over 1 year. Registration: URL: https://www.ClinicalTrials.gov. Unique Identifier: NCT02396758.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434215PMC
August 2020

A fortune teller's dream or clinician's nightmare: Right ventricular assessment for risk prediction in pulmonary embolism.

Authors:
Gregory Piazza

Thromb Res 2020 11 16;195:169-170. Epub 2020 Jul 16.

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2020.07.032DOI Listing
November 2020

Coagulation Status and Venous Thromboembolism Risk in African Americans: A Potential Risk Factor in COVID-19.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620943671

Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.
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http://dx.doi.org/10.1177/1076029620943671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383642PMC
July 2020

Predictors of Treatment Response Following Ultrasound-Facilitated Catheter-Directed Thrombolysis for Submassive and Massive Pulmonary Embolism: A SEATTLE II Substudy.

Circ Cardiovasc Interv 2020 06 10;13(6):e008747. Epub 2020 Jun 10.

Warren Alpert Medical School at Brown University/Lifespan Cardiovascular Institute, Providence, RI (P. Soukas, H.D.A.).

Background: Little is known about which factors predict improvement in clinical and imaging parameters among patients undergoing catheter-directed thrombolysis for submassive or massive pulmonary embolism. The identification of such predictors may allow for more appropriate patient selection for ultrasound-facilitated catheter-directed thrombolysis.

Methods: We conducted a retrospective cohort analysis of patients from the SEATTLE II trial (Prospective, Single-Arm, Multi-Center Trial of EkoSonic Endovascular System and Activase for Treatment of Acute Pulmonary Embolism) to identify clinical characteristics that independently predict pulmonary artery pressures, right ventricular-to-left ventricular (RV/LV) diameter ratio, and modified Miller angiographic index following ultrasound-assisted catheter-directed thrombolysis. Eligible patients had submassive or massive pulmonary embolism and an RV/LV diameter ratio ≥0.9 on chest computed tomography. Multivariable linear regression was used to identify independent clinical predictors of each outcome.

Results: One hundred fifty patients with massive (n=31) or submassive (n=119) pulmonary embolism were enrolled. Mean (±SD) baseline and postprocedure RV/LV diameter ratio, pulmonary artery systolic pressure, and modified Miller Score were 1.59 (±0.39) and 1.14 (±0.2), 51.45 (±16.0), and 37.47 (±11.9), and 23.0 (±5.7) and 15.7 (±5.9), respectively. The multivariable model adjusted for absolute change in RV/LV ratio, pulmonary artery systolic pressure, modified Miller Score was 0.71, 0.57, and 0.43, respectively. After adjusting for age, gender, and baseline RV/LV ratio, pulmonary artery systolic pressure, and modified Miller Score, patients with higher body mass index, renal or hepatic dysfunction, active smoking, or a higher baseline heart rate showed less improvement.

Conclusions: Patients with more life-threatening pulmonary embolism may derive the greatest benefit from ultrasound-assisted, catheter-directed thrombolysis.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008747DOI Listing
June 2020

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

Thromb Haemost 2020 Jul 30;120(7):1004-1024. Epub 2020 May 30.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.
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http://dx.doi.org/10.1055/s-0040-1713152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516364PMC
July 2020

Development of Sex-Stratified Prediction Models for Recurrent Venous Thromboembolism: A Danish Nationwide Cohort Study.

Thromb Haemost 2020 May 5;120(5):805-814. Epub 2020 May 5.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Objective:  To optimize decision making for anticoagulant treatment duration after incident venous thromboembolism, we derived and internally validated two clinically applicable sex-specific prediction models for venous thromboembolism recurrence, discarding the traditional categorization of provoked and unprovoked venous thromboembolism.

Methods:  This study was based on data from Danish nationwide registries. We identified all routine care in- and outpatients with completed anticoagulant treatment for incident venous thromboembolism from 2012 through 2017. The outcome was recurrent venous thromboembolism within 2 years. Risk scores were derived using Cox regression analysis and a backward selection process on a set of 24 potential predictors. Performance was assessed through calibration and discrimination using bootstrap techniques to internally validate the scores.

Results:  The study included 11,519 patients. Risk scores under the joint acronym AIM-SHA-RP were developed. ge, ncident pulmonary embolism, and recent ajor surgery were predictors for both sexes; tatin treatment, eart disease and ntiplatelet treatment were predictors specifically for men, while chronic enal disease and recent neumonia or sepsis were predictors specifically for women. The risk scores were well calibrated and identified a low- (< 5%), intermediate- (5-10%), and high-risk (> 10%) group for both sexes. Generally, discriminative capacities, as measured by the -statistic, were limited.

Conclusion:  We developed two clinically applicable risk scores to estimate the risk of recurrent venous thromboembolism after completed anticoagulant treatment. The risk scores can potentially guide treatment duration of anticoagulation after incident venous thromboembolism but require further external validation before implemented in clinical practice.
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http://dx.doi.org/10.1055/s-0040-1708877DOI Listing
May 2020

Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients: An NATF Anticoagulation Action Initiative.

Am J Med 2020 05;133 Suppl 1:1-27

Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.

Hospitalized patients with acute medical illnesses are at risk for venous thromboembolism (VTE) during and after a hospital stay. Risk factors include physical immobilization and underlying pathophysiologic processes that activate the coagulation pathway and are still present after discharge. Strategies for optimal pharmacologic VTE thromboprophylaxis are evolving, and recommendations for VTE prophylaxis can be further refined to protect high-risk patients after hospital discharge. An early study of extended VTE prophylaxis with a parenteral agent in medically ill patients yielded inconclusive results with regard to efficacy and bleeding. In the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial, extended use of betrixaban halved symptomatic VTE, decreased hospital readmission, and reduced stroke and major adverse cardiovascular events compared with standard enoxaparin prophylaxis. Based on findings from APEX, the Food and Drug Administration approved betrixaban in 2017 for extended VTE prophylaxis in acute medically ill patients. In the Reducing Post-Discharge Venous Thrombo-Embolism Risk (MARINER) study, extended use of rivaroxaban halved symptomatic VTE in high-risk medical patients compared with placebo. In 2019, rivaroxaban was approved for extended thromboprophylaxis in high-risk medical patients, thus making available a new strategy for in-hospital and post-discharge VTE prevention. To address the critical unmet need for VTE prophylaxis in medically ill patients at the time of hospital discharge, the North American Thrombosis Forum (NATF) is launching the Anticoagulation Action Initiative, a comprehensive consensus document that provides practical guidance and straightforward, patient-centered recommendations for VTE prevention during hospitalization and after discharge.
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http://dx.doi.org/10.1016/j.amjmed.2019.12.001DOI Listing
May 2020

Listen to Your Heart (but DON'T Look at Theirs): Risk Assessment for Home Treatment of Pulmonary Embolism.

Authors:
Gregory Piazza

Am J Respir Crit Care Med 2020 07;202(1):20-21

Department of MedicineBrigham and Women's Hospital and Harvard Medical SchoolBoston, Massachusetts.

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http://dx.doi.org/10.1164/rccm.202004-0978EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328336PMC
July 2020

Primary prevention of venous thromboembolism with apixaban for multiple myeloma patients receiving immunomodulatory agents.

Br J Haematol 2020 08 21;190(4):555-561. Epub 2020 Apr 21.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Immunomodulatory drugs (IMiDs) have improved survival of patients with multiple myeloma (MM) and comprise the therapeutic backbone at all phases of therapy. Although well-tolerated, IMiDs increase rates of venous thromboembolism (VTE). In this phase IV, single-arm pilot study, fifty patients with MM on IMiDs received apixaban 2·5 mg orally twice daily for primary prevention of VTE and were prospectively monitored for six months. The primary safety outcomes were rates of major haemorrhage and clinically relevant non-major haemorrhage over six months. The primary efficacy outcome was the rate of symptomatic VTE over six months. IMiDs used were lenalidomide (58%) or pomalidomide (42%). During the six-month evaluation period, no patients experienced major haemorrhage or VTE. Three patients experienced clinically relevant, non-major haemorrhage which was managed medically, and all were able to resume apixaban. One patient stopped therapy shortly after initiation due to an allergic reaction to apixaban. No patients experienced stroke, myocardial infarction, or death. In this pilot study, low-dose apixaban was safe and well-tolerated as a primary prevention therapy of VTE for patients with MM receiving IMiDs. Further studies are needed to validate low-dose apixaban as a standard primary prevention anti-thrombotic strategy for patients with MM receiving IMiDs.
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http://dx.doi.org/10.1111/bjh.16653DOI Listing
August 2020

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review.

J Am Coll Cardiol 2020 06 17;75(23):2950-2973. Epub 2020 Apr 17.

Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom; Aalborg University, Aalborg, Denmark.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.jacc.2020.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164881PMC
June 2020

Extended oral anticoagulation after incident venous thromboembolism - a paradigm shift?

Expert Rev Cardiovasc Ther 2020 Apr 26;18(4):201-208. Epub 2020 Apr 26.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

: Patients with incident venous thromboembolism carry a chronic risk of suffering a recurrent event. Anticoagulation is effective at preventing recurrence during treatment but also associated with risk of bleeding. Hence, the dilemma of optimal anticoagulant treatment duration beyond the acute treatment phase remains a clinical challenge in the management of venous thromboembolism.: This review summarizes the current evidence for extended oral anticoagulant treatment after incident venous thromboembolism, and discusses dilemmas involved in treatment decisions related to extended secondary prevention.: Results from landmark venous thromboembolism-extended treatment studies focused on direct oral anticoagulants suggest a paradigm shift of the risk-benefit balance in favor of extended anticoagulant treatment. Nevertheless, patient preferences need to be considered while persistent concerns about enduring risk of bleeding must be addressed for the new paradigm to be implemented into clinical practice.
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http://dx.doi.org/10.1080/14779072.2020.1755260DOI Listing
April 2020

Running thin: implications of a heparin shortage.

Lancet 2020 02 23;395(10223):534-536. Epub 2020 Jan 23.

Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1016/S0140-6736(19)33135-6DOI Listing
February 2020

Predictors of Not Initiating Anticoagulation After Incident Venous Thromboembolism: A Danish Nationwide Cohort Study.

Am J Med 2020 04 10;133(4):463-472.e5. Epub 2019 Oct 10.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Aalborg Thrombosis Research Unit, Aalborg University Hospital, Aalborg, Denmark.

Purpose: The purpose of this study was to investigate potential predictors associated with not initiating anticoagulation after incident venous thromboembolism.

Methods: We linked Danish nationwide health registries to identify all patients with incident venous thromboembolism from 2003 through 2016. We defined treatment noninitiation as not claiming a prescription for an anticoagulant drug within 30 days after hospital discharge. To identify potential predictors of noninitiation, relative risks (RRs) with 95% confidence intervals (CIs) were calculated adjusting for other compliance-related factors.

Results: The study included 38,044 patients with incident venous thromboembolism (53.2% female and median age 66.1 years). Of these, 24.1% (n = 9294) were noninitiators. Demographic and condition-related factors that predicted noninitiation included: female sex (RR 1.30; 95% CI, 1.25-1.34), age <30 vs age >65 years (RR 1.18; 95% CI, 1.13-1.33), hospitalization 0-3 days vs >3 days (RR 1.96; 95% CI, 1.87-2.07), incident deep venous thrombosis (RR 1.91; 95% CI, 1.81-2.01), and unprovoked venous thromboembolism (RR 1.13; 95% CI, 1.08-1.17). Socioeconomic factors had less influence on risk of noninitiation. Individual chronic diseases predictive of noninitiation included congestive heart failure (RR 1.27; 95% CI, 1.17-1.37), ischemic heart disease (RR 1.20; 95% CI, 1.13-1.28), and liver disease (RR 1.60; 95% CI, 1.42-1.81).

Conclusion: Up to one-fourth of patients diagnosed with incident venous thromboembolism did not initiate anticoagulant treatment within 30 days after hospital discharge. Identification of clinical predictors of noninitiation may enable implementation of patient-tailored strategies to improve adherence and thereby potentially prevent venous thromboembolism morbidity, mortality, and recurrence.
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http://dx.doi.org/10.1016/j.amjmed.2019.08.051DOI Listing
April 2020

Interventional Therapies for Acute Pulmonary Embolism: Current Status and Principles for the Development of Novel Evidence: A Scientific Statement From the American Heart Association.

Circulation 2019 11 4;140(20):e774-e801. Epub 2019 Oct 4.

Pulmonary embolism (PE) represents the third leading cause of cardiovascular mortality. The technological landscape for management of acute intermediate- and high-risk PE is rapidly evolving. Two interventional devices using pharmacomechanical means to recanalize the pulmonary arteries have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. The purpose of this document is to clarify the current state of endovascular interventional therapy for acute PE and to provide considerations for evidence development for new devices that will define which patients with PE would derive the greatest net benefit from their use in various clinical settings. First, definitions and limitations of commonly used risk stratification tools for PE are reviewed. An adjudication of risks and benefits of available interventional therapies for PE follows. Next, considerations for optimal future evidence development in this field are presented in the context of the current US regulatory framework. Finally, the document concludes with a discussion of the pros and cons of the rapidly expanding PE response team model of care delivery.
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http://dx.doi.org/10.1161/CIR.0000000000000707DOI Listing
November 2019

Collaborative Cardiology and Pulmonary Management of Pulmonary Hypertension.

Chest 2019 08;156(2):200-202

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1016/j.chest.2019.04.099DOI Listing
August 2019