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1.
Clin Appl Thromb Hemost ; 27: 10760296211066945, 2021.
Article in English | MEDLINE | ID: covidwho-1574469

ABSTRACT

INTRODUCTION: Argatroban is licensed for patients with heparin-induced thrombocytopenia and is conventionally monitored by activated partial thromboplastin time (APTT) ratio. The target range is 1.5 to 3.0 times the patients' baseline APTT and not exceeding 100 s, however this baseline is not always known. APTT is known to plateau at higher levels of argatroban, and is influenced by coagulopathies, lupus anticoagulant and raised FVIII levels. It has been used as a treatment for COVID-19 and Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). Some recent publications have favored the use of anti-IIa methods to determine the plasma drug concentration of argatroban. METHODS: Plasma of 60 samples from 3 COVID-19 patients and 54 samples from 5 VITT patients were tested by APTT ratio and anti-IIa method (dilute thrombin time dTT). Actin FS APTT ratios were derived from the baseline APTT of the patient and the mean normal APTT. RESULTS: Mean APTT ratio derived from baseline was 1.71 (COVID-19), 1.33 (VITT) compared to APTT ratio by mean normal 1.65 (COVID-19), 1.48 (VITT). dTT mean concentration was 0.64 µg/ml (COVID-19) 0.53 µg/ml (VITT) with poor correlations to COVID-19 baseline APTT ratio r2 = 0.1526 p <0.0001, mean normal r2 = 0.2188 p < 0.0001; VITT baseline APTT ratio r2 = 0.04 p < 0.001, VITT mean normal r2 = 0.0064 p < 0.001. CONCLUSIONS: We believe that dTT is a superior method to monitor the concentration of argatroban, we have demonstrated significant differences between APTT ratios and dTT levels, which could have clinical impact. This is especially so in COVID-19 and VITT.


Subject(s)
Arginine/analogs & derivatives , COVID-19/drug therapy , Partial Thromboplastin Time/methods , Pipecolic Acids/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Sulfonamides/therapeutic use , Thrombocytopenia/drug therapy , Thrombosis/drug therapy , Aged , Arginine/pharmacology , Arginine/therapeutic use , COVID-19/complications , Female , Humans , Male , Middle Aged , Pipecolic Acids/pharmacology , Platelet Aggregation Inhibitors/pharmacology , SARS-CoV-2 , Sulfonamides/pharmacology , Thrombocytopenia/chemically induced , Thrombosis/chemically induced
2.
JAMA ; 326(17): 1703-1712, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1525396

ABSTRACT

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thrombosis/prevention & control , Adult , Aspirin/adverse effects , COVID-19/complications , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects
3.
Clin Appl Thromb Hemost ; 27: 10760296211048808, 2021.
Article in English | MEDLINE | ID: covidwho-1495924

ABSTRACT

We aimed to investigate association between mean platelet volume (MVP), platelet distribution width (PDW) and red cell distribution width (RDW) and mortality in patients with COVID-19 and find out in which patients the use of acetylsalicylic acid (ASA) affects the prognosis due to the effect of MPV on thromboxan A2. A total of 5142 patients were divided into those followed in the intensive care unit (ICU) and those followed in the ward. Patient medical records were examined retrospectively. ROC analysis showed that the area under curve (AUC) values were 0.714, 0.750, 0.843 for MPV, RDW and D-Dimer, the cutoff value was 10.45fl, 43.65fl, 500.2 ng/mL respectively. (all P < .001). Survival analysis showed that patients with MPV >10.45 f/l and D-Dimer >500.2 ng/mL, treatment with ASA had lower in-hospital and 180-day mortality than patients without ASA in ICU patients (HR = 0.773; 95% CI = 0.595-0.992; P = .048, HR = 0.763; 95% CI = 0.590-0.987; P = .036). Administration of low-dose ASA in addition to anti-coagulant according to MPV and D-dimer levels reduces mortality.


Subject(s)
Blood Platelets , COVID-19/blood , Erythrocyte Indices , Erythrocytes , Mean Platelet Volume , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Blood Platelets/drug effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Predictive Value of Tests , Retrospective Studies , Severity of Illness Index , Time Factors , Treatment Outcome
4.
JAMA ; 326(17): 1703-1712, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1460106

ABSTRACT

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thrombosis/prevention & control , Adult , Aspirin/adverse effects , COVID-19/complications , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects
5.
Open Heart ; 8(2)2021 10.
Article in English | MEDLINE | ID: covidwho-1455738

ABSTRACT

BACKGROUND: COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population. METHODS: A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation. RESULTS: 242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation. CONCLUSION: The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/therapy , Platelet Aggregation Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/complications , COVID-19/mortality , Female , Hospital Mortality , Humans , Inpatients , Intensive Care Units , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Survival Analysis , Thromboembolism/drug therapy , Thromboembolism/physiopathology , Thrombosis/drug therapy , Thrombosis/physiopathology , Treatment Outcome
7.
J Med Virol ; 93(9): 5390-5395, 2021 09.
Article in English | MEDLINE | ID: covidwho-1363677

ABSTRACT

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , SARS-CoV-2/pathogenicity , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Coronary Artery Disease/complications , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Drug Combinations , Female , Hospital Mortality , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Hypertension/virology , Iran , Lopinavir/therapeutic use , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/virology , Respiration, Artificial/mortality , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , Severity of Illness Index , Survival Analysis , Treatment Outcome
9.
Pharmacol Res ; 158: 104950, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318942

ABSTRACT

Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels. Both hypoxemia and a prothrombotic diathesis have been associated with more severe disease and increased risk of death. To date, specific indications to treat this condition are lacking. This was a single center, investigator initiated, compassionate use, proof of concept, case control, phase IIb study (NCT04368377) conducted in the Intermediate Respiratory Care Unit of L. Sacco University Hospital in Milano, Italy. Our objective was to explore the effects of the administration of anti-platelet therapy on arterial oxygenation and clinical outcomes in patients with severe Covid-19 with hypercoagulability. We enrolled five consecutive patients with laboratory confirmed SARS-CoV-2 infection, severe respiratory failure requiring helmet continuous positive airway pressure (CPAP), bilateral pulmonary infiltrates and a pro-thrombotic state identified as a D-dimer > 3 times the upper limit of normal. Five patients matched for age, D-dimer value and SOFA score formed the control group. Beyond standard of care, treated patients received 25 µg/Kg/body weight tirofiban as bolus infusion, followed by a continuous infusion of 0.15 µg/Kg/body weight per minute for 48 hours. Before tirofiban, patients received acetylsalicylic acid 250 mg infusion and oral clopidogrel 300 mg; both were continued at a dose of 75 mg daily for 30 days. Fondaparinux2.5 mg/day sub-cutaneous was given for the duration of the hospital stay. All controls were receiving prophylactic or therapeutic dose heparin, according to local standard operating procedures. Treated patients consistently experienced a mean (SD) reduction in A-a O2 gradient of -32.6 mmHg (61.9, P = 0.154), -52.4 mmHg (59.4, P = 0.016) and -151.1 mmHg (56.6, P = 0.011; P = 0.047 vs. controls) at 24, 48 hours and 7 days after treatment. PaO2/FiO2 ratio increased by 52 mmHg (50, P = 0.172), 64 mmHg (47, P = 0.040) and 112 mmHg (51, P = 0.036) after 24, 48 hours and 7 days, respectively. All patients but one were successfully weaned from CPAP after 3 days. This was not true for the control group. No major adverse events were observed. Antiplatelet therapy might be effective in improving the ventilation/perfusion ratio in Covid-19 patients with severe respiratory failure. The effects might be sustained by the prevention and interference on forming clots in lung capillary vessels and by modulating megakaryocytes' function and platelet adhesion. Randomized clinical trials are urgently needed to confirm these results.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Hypoxia/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Thrombophilia/drug therapy , Aged , Aspirin/therapeutic use , COVID-19 , Clopidogrel/therapeutic use , Compassionate Use Trials , Coronavirus Infections/complications , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypoxia/complications , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Proof of Concept Study , SARS-CoV-2 , Thrombophilia/blood , Thrombophilia/complications , Tirofiban/therapeutic use
10.
Stroke Vasc Neurol ; 5(3): 279-284, 2020 09.
Article in English | MEDLINE | ID: covidwho-1318202

ABSTRACT

BACKGROUND AND PURPOSE: COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19. Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection. MATERIALS AND METHODS: Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed. Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared. RESULTS: Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage. COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05). In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001). Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died. The other four patients received anticoagulant treatment with enoxaparin and 2 of them died. As of 24 March 2020, six patients with CVD died (54.5%). CONCLUSION: Acute CVD is not uncommon in COVID-19. Our findings suggest that older patients with risk factors are more likely to develop CVD. The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.


Subject(s)
Betacoronavirus/pathogenicity , Cerebrovascular Disorders/virology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Acute Disease , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , COVID-19 , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/mortality , China , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Treatment Outcome
12.
Open Heart ; 8(1)2021 06.
Article in English | MEDLINE | ID: covidwho-1255621

ABSTRACT

BACKGROUND: Patients with type 2 myocardial infarction (T2MI) and other mechanisms of nonthrombotic myocardial injury have an unmet therapeutic need. Eligibility for novel medical therapy is generally uncertain. METHODS: We predefined colchicine, eplerenone and ticagrelor as candidates for repurposing towards novel therapy for T2MI or myocardial injury. Considering eligibility for randomisation in a clinical trial, each drug was classified according to indications and contraindications for therapy and survival for at least 24 hours following admission. Eligibility criteria for prescription were evaluated against the Summary of Medical Product Characteristics. Consecutive hospital admissions were screened to identify patients with ≥1 high-sensitivity troponin-I value >99th percentile. Endotypes of myocardial injury were adjudicated according to the Fourth Universal Definition of MI. Patients' characteristics and medication were prospectively evaluated. RESULTS: During 1 March to 15 April 2020, 390 patients had a troponin I>URL. Reasons for exclusion: type 1 MI n=115, indeterminate diagnosis n=42, lack of capacity n=14, death <24 hours n=7, duplicates n=2. Therefore, 210 patients with T2MI/myocardial injury and 174 (82.8%) who survived to discharge were adjudicated for treatment eligibility. Patients who fulfilled eligibility criteria initially on admission and then at discharge were colchicine 25/210 (11.9%) and 23/174 (13.2%); eplerenone 57/210 (27.1%) and 45/174 (25.9%); ticagrelor 122/210 (58.1%) and 98/174 (56.3%). Forty-six (21.9%) and 38 (21.8%) patients were potentially eligible for all three drugs on admission and discharge, respectively. CONCLUSION: A reasonably high proportion of patients may be considered eligible for repurposing novel medical therapy in secondary prevention trials of type 2 MI/myocardial injury.


Subject(s)
Anterior Wall Myocardial Infarction/drug therapy , Colchicine/therapeutic use , Eplerenone/therapeutic use , Myocardium/metabolism , Patient Selection , Ticagrelor/therapeutic use , Troponin I/blood , Anterior Wall Myocardial Infarction/blood , Anterior Wall Myocardial Infarction/diagnosis , Anterior Wall Myocardial Infarction/therapy , Biomarkers/blood , Female , Follow-Up Studies , Humans , Male , Mineralocorticoid Receptor Antagonists/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Retrospective Studies , Tubulin Modulators/therapeutic use
13.
J Investig Med High Impact Case Rep ; 8: 2324709620963567, 2020.
Article in English | MEDLINE | ID: covidwho-1223701

ABSTRACT

The incidence of mechanical valve thrombosis (MVT) is around 0.4 per 100 patient-years. Mitral valve thrombosis has a higher incidence than aortic valve thrombosis with a nearly 5-fold increase. Various factors contribute to MVT. The most common cause of valve thrombosis is poor adherence/disruption of anticoagulation therapy. Low cardiac output is known to increase the risk of prosthetic valve thrombosis. Other factors such as diabetes, hypertension, and other patient comorbidities might also play a role. Decreased flow promotes hypercoagulability. Lower pressure in the left atrium (and higher velocities in the left ventricle) can partially contribute to the higher incidence of mitral MVT versus aortic MVT. The presenting symptoms usually depend on the severity of the valve thrombosis; nonobstructive valve thrombosis patients have progressive dyspnea, signs of heart failure, and systemic embolization with strokes being the most common complication. In this article, we present a case of a middle-aged woman with a history of mitral and aortic mechanical prosthesis who presented with an ST-segment elevation myocardial infarction and pulmonary edema due to mechanical aortic valve prosthesis thrombosis. She had an isolated mechanical aortic valve prosthesis thrombosis with intact mitral valve, which, to the best of our knowledge, has not yet been described. We performed a literature review by searching PubMed and Embase using the keywords "mechanical valve," "thrombosis," "aortic," and "mitral," our search did not show similar cases.


Subject(s)
Aortic Valve , Heart Valve Prosthesis/adverse effects , Mitral Valve , ST Elevation Myocardial Infarction/etiology , Thrombosis/drug therapy , Cardiac Output, Low , Coronary Angiography , Echocardiography , Female , Fibrinolytic Agents/therapeutic use , Humans , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Edema/diagnosis , Pulmonary Edema/drug therapy , ST Elevation Myocardial Infarction/drug therapy , Thrombosis/diagnosis
14.
J Am Heart Assoc ; 10(3): e019650, 2021 02 02.
Article in English | MEDLINE | ID: covidwho-1221678

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2, which has posed a significant threat to global health. Although the infection is frequently asymptomatic or associated with mild symptoms, in a small proportion of patients it can produce an intense inflammatory and prothrombotic state that can lead to acute respiratory distress syndrome, multiple organ failure, and death. Angiotensin-converting enzyme 2, highly expressed in the respiratory system, has been identified as a functional receptor for severe acute respiratory syndrome coronavirus-2. Notably, angiotensin-converting enzyme 2 is also expressed in the cardiovascular system, and there are multiple cardiovascular implications of COVID-19. Cardiovascular risk factors and cardiovascular disease have been associated with severe manifestations and poor prognosis in patients with COVID-19. More important, patients with COVID-19 may have thrombotic and coagulation abnormalities, promoting a hypercoagulable state and resulting in an increased rate of thrombotic and thromboembolic events. This review will describe the pathophysiological characteristics of the cardiovascular involvement following infection by severe acute respiratory syndrome coronavirus-2, with a focus on thrombotic and thromboembolic manifestations and implications for antithrombotic management.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Fibrinolytic Agents/therapeutic use , Pandemics , Platelet Aggregation Inhibitors/therapeutic use , Thromboembolism/prevention & control , COVID-19/epidemiology , Humans , Thromboembolism/etiology , Treatment Outcome
15.
Ann Vasc Surg ; 75: 128-135, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1210815

ABSTRACT

Investigations have shown that infection from the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is responsible also for initiating severe inflammatory responses that can lead macrovascular and microvascular thrombosis. Several studies have already described acute limb ischemia and peripheral arterial disease in critically ill patients with Coronavirus disease 2019 (Covid-19), as well as coronary artery disease and ischemic stroke as a manifestation usually associated with respiratory distress. However, what still remains unclear is how long inflammation and thrombotic derangements can last after recovery from the symptoms of Covid-19. Hence, in this article we report 3 cases of arterial thrombotic sequalae after this viral infection. To the best of our knowledge, this is the first cases' series that had described different delayed vascular arterial complications, which occurred after the index infection, with a negative nasopharyngeal swab and Covid-19 systemic symptoms resumption. A better understanding of the coagulopathy in Covid-19 could have an essential role to guide prevention and treatment of arterial thromboembolic events, both during and after the viral infection. Further investigations are required to confirm these data and to estabilish the type, dose and duration of anticoagulant/antiplatelet therapy not just during but also after Covid-19 infection.


Subject(s)
Arterial Occlusive Diseases/etiology , COVID-19/complications , Thrombosis/etiology , Aged , Anticoagulants/therapeutic use , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/drug therapy , COVID-19/diagnosis , COVID-19/therapy , Female , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Risk Factors , Thrombolytic Therapy , Thrombosis/diagnostic imaging , Thrombosis/drug therapy , Time Factors , Treatment Outcome
16.
J Med Virol ; 93(9): 5390-5395, 2021 09.
Article in English | MEDLINE | ID: covidwho-1206845

ABSTRACT

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , SARS-CoV-2/pathogenicity , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Coronary Artery Disease/complications , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Drug Combinations , Female , Hospital Mortality , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Hypertension/virology , Iran , Lopinavir/therapeutic use , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/virology , Respiration, Artificial/mortality , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , Severity of Illness Index , Survival Analysis , Treatment Outcome
17.
Blood Coagul Fibrinolysis ; 32(3): 167-171, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1171412

ABSTRACT

Coronavirus disease 2019 infection produce a prothrombotic state. This is initiated through multiple pathways and is finally aggravated by cross talks with cytokine storm and neutrophil, platelet, complement activation. All these combine towards the second week of illness to produce thrombosis in the lung capillaries surrounding the alveolus producing characteristic pulmonary dysfunction (PaO2/FiO2 > 300, normal or minimally increased lung compliance and very high d-dimer levels) and a high rate of peripheral venous thrombosis. International and many national guidelines have approached this state in different ways but all emphasized the need for management and prevention of widespread thrombosis. It is felt more aggressive and graded thrombosis prevention and management should be initiated early in the treatment. d-Dimer, neutrophil count, SaO2, fibrinogen levels should be used to control the hypercoagulability. Drugs like statins which have anti-inflammatory action as well as ability to reduce fibrinogen and other clotting factors should be used in the beginning along with antiplatelet drugs and progressively complement activation and neutrophil extracellular traps inhibitors, oral mucopolysaccharides, full-scale anticoagulation along with judicial use of fibrinolysis supporting drugs should be added. In the present review, we have evaluated the various studies and argued the rationality that the anticoagulation in this condition should be initiated early during the infection and should be increased in a graded manner depending on clinical and laboratory progression of the condition until a strong specific antiviral drug for coronavirus disease 2019 infection is available.


Subject(s)
Blood Coagulation/drug effects , COVID-19/drug therapy , COVID-19/physiopathology , Thrombophilia/drug therapy , Thrombosis/drug therapy , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Extracellular Traps/drug effects , Fibrinolytic Agents/therapeutic use , Glycosaminoglycans/pharmacology , Glycosaminoglycans/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation/drug therapy , Lung/drug effects , Lung/physiopathology , Lung/virology , Platelet Aggregation Inhibitors/therapeutic use
18.
Br J Hosp Med (Lond) ; 82(3): 1-9, 2021 Mar 02.
Article in English | MEDLINE | ID: covidwho-1168180

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread and have grave health and socioeconomic consequences worldwide. Researchers have raced to understand the pathophysiological mechanisms underpinning the disease caused by SARS-CoV-2 so that effective therapeutic targets can be discovered. This review summarises the key pharmacotherapies that are being investigated for treatment of COVID-19, including antiviral, immunomodulator and anticoagulation strategies.


Subject(s)
Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , Immunologic Factors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azetidines/therapeutic use , COVID-19/therapy , Colchicine/therapeutic use , Dexamethasone/therapeutic use , Humans , Immunization, Passive , Ivermectin/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , SARS-CoV-2 , Sulfonamides/therapeutic use
20.
Anesth Analg ; 132(4): 930-941, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1136265

ABSTRACT

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. To our knowledge, no studies have evaluated whether aspirin use is associated with reduced risk of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. METHODS: A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. RESULTS: Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. CONCLUSIONS: Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.


Subject(s)
Aspirin/therapeutic use , COVID-19/therapy , Fibrinolytic Agents/therapeutic use , Intensive Care Units , Patient Admission , Platelet Aggregation Inhibitors/therapeutic use , Respiration, Artificial , Adult , Aged , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States
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