Research into New Molecular Mechanisms in Thrombotic Diseases Paves the Way for Innovative Therapeutic Approaches.

Thrombosis is a multifaceted process involving various molecular components, including the coagulation cascade, platelet activation, platelet-endothelial interaction, anticoagulant signaling pathways, inflammatory mediators, genetic factors and the involvement of various cells such as endothelial cells, platelets and leukocytes. A comprehensive understanding of the molecular signaling pathways and cell interactions that play a role in thrombosis is essential for the development of precise therapeutic strategies for the treatment and prevention of thrombotic diseases. Ongoing research in this field is constantly uncovering new molecular players and pathways that offer opportunities for more precise interventions in the clinical setting. These molecular insights into thrombosis form the basis for the development of targeted therapeutic approaches for the treatment and prevention of thrombotic disease. The aim of this review is to provide an overview of the pathogenesis of thrombosis and to explore new therapeutic options.

Potential role of cardiopulmonary exercise testing in evaluating functional improvement after transcatheter edge-to-edge tricuspid valve repair: a case report.

Background: Tricuspid regurgitation (TR) is common and severe or greater TR is linked to poor prognosis. Treatment of TR with transcatheter edge-to-edge repair has emerged as a safe and potentially effective therapy in these patients. However, the impact of transcatheter tricuspid repair on functional capacity remains to be elucidated. Case summary: We describe the case of a 77-year-old woman complaining of heart failure symptoms, undergoing transcatheter edge-to-edge valve repair for severe TR with the PASCAL Ace® device. One month later, cardiopulmonary exercise testing (CPET) showed significant improvement in peak O2 uptake and O2 pulse compared with the test performed before the procedure. Discussion: A positive impact of novel transcatheter edge-to-edge valve repair on symptoms and quality of life in patients with severe or greater TR at prohibitive surgical risk has recently emerged. The presence of severe TR has prognostic relevance, and novel percutaneous tricuspid valve repair systems have emerged in the last few years. Cardiopulmonary exercise testing is an established tool to assess functional capacity and prognosis in heart failure patient. Detecting functional capacity improvement after transcatheter edge-to-edge repair for severe TR can be challenging, and CPET may arise as a promising tool to help these purposes.

Statins as preventive therapy for anthracycline cardiotoxicity: a meta-analysis of randomized controlled trials.

BACKGROUND: Cardiotoxicity occurs in 5-20% of cancer patients who receive anthracyclines. The aim of this study was to pool all the randomized controlled trials (RCTs) investigating the cardio-protective role of statins in patients treated with anthracyclines. METHODS: PubMed and Scopus electronic databases were scanned for eligible studies up to May 3rd, 2023. A total of 5 RCTs with 808 patients were included. Efficacy endpoints were the rate of anthracycline-mediated cardiotoxicity, the incidence of hospitalization for heart failure (HF), left ventricular ejection fraction (LVEF) value after anthracycline treatment, and ∆LVEF calculated as the difference in LVEF before and after anthracycline therapy. Safety endpoints [i.e., the incidence of muscle pain and serious adverse events (SAE)] were also assessed. RESULTS: On pooled analysis, the statin-treated group had a lower incidence of cardiotoxicity compared to the placebo group [risk ratio (RR) 0.52, 95% confidence Interval (CI) 0.33-0.83, P = 0.01; I2 = 0%], as well as higher mean LVEF [Mean difference (MD) 1.88, 95% CI 0.66-3.1, P < 0.01; I2 = 57.3%)] and a more favorable ∆LVEF during follow-up (MD 2.38, 95% CI -0.03 - +4.79, P = 0.05; I2 = 99%), despite no significant difference in terms of hospitalization for HF and rate of adverse events. Of note, severe heterogeneity affected the analyses for both LVEF and ΔLVEF. CONCLUSIONS: The current meta-analysis of all RCTs conducted so far shows an overall beneficial effect of statins on the risk of anthracyclines-induced cardiotoxicity and LVEF preservation. No difference was observed in the rate of HF hospitalization. More powered RCTs are needed to fully investigate the impact of statins on prognosis in patients receiving anthracyclines therapy.

[Proposal for a diagnostic and therapeutic care pathway of the Piedmont Region on lipid-lowering and antithrombotic treatment in patients with peripheral arterial disease]. / Proposta di percorso diagnostico-terapeutico assistenziale della Regione Piemonte sulla terapia ipolipemizzante ed antitrombotica in pazienti con malattia delle arterie periferiche.

The aim of this paper is to present the diagnostic and therapeutic care pathway on peripheral arterial disease, recently developed in the Piedmont Region, Italy. It proposes a combined approach between the cardiologist and vascular surgeon for optimizing the treatment of patients with peripheral artery disease, which includes the most recently approved antithrombotic and lipid-lowering drugs. The goal is to promote a greater awareness on peripheral vascular disease, in order to implement its treatment patterns and consequently to perform an effective secondary cardiovascular prevention.

Predictive Value of Echocardiographic Pulmonary to Left Atrial Ratio for In-Hospital Death in Patients with COVID-19.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

Safety and efficacy of very low LDL-cholesterol intensive lowering: a meta-analysis and meta-regression of randomized trials.

AIMS: We performed a study-level meta-analysis to provide more robust evidence on safety of very low LDL-cholesterol (LDL-C) levels. BACKGROUND: Concerns on the safety of LDL-C values achieved with potent lipid-lowering therapies have been raised. METHODS AND RESULTS: We searched randomized trials reporting clinical outcomes with intensive lipid-lowering treatments leading to very low (<40 mg/dL) LDL-C levels vs. a control group with higher LDL-C levels. Only studies with follow-up duration ≥ 3 months were considered. Primary endpoint was the incidence of various safety measures. A total of 10 randomized trials were overall included, with 38 427 patients being in the very low LDL-C group vs. 70 668 in the control group. Median follow-up duration was 28.8 months. The incidence of all safety outcomes was similar in the two groups: non-cardiovascular death: OR 1.13, 95% CI 0.87-1.45; P = 0.36; any adverse events: OR 1.00, 0.90-1.11, P = 0.94; adverse events leading to drug discontinuation: OR 1.00, 0.87-1.15, P = 0.99; cancer: OR 1.02, 0.95-1.10, P = 0.57; haemorrhagic stroke OR 0.89, 0.66-1.20, P = 0.44; new-onset diabetes: OR 1.16, 0.91-1.47, P = 0.23; neurocognitive disorders: OR 0.97, 0.91-1.04, P = 0.41; haepatobiliary disorders: OR 0.99, 0.83-1.18, P = 0.93; muscle disorders: OR 0.94, 0.77-1.13, P = 0.49; cataract: OR 1.28, 0.78-2.10, P = 0.34. The rates of major adverse cardiovascular events were significantly lower in the very low LDL-C group: OR 0.82, 0.72-0.94, P = 0.005. CONCLUSION: This meta-analysis indicates that very low LDL-C levels on intensive lipid-lowering treatments are not associated with any adverse event and maintain a persistent reduction of cardiovascular events.

Unmasking of a significant left main stenosis in a patient with high left ventricular pressures.

As identification of left main (LM) stenoses has prognostic and therapeutic relevance, a precise anatomic and/or functional characterization of angiographically intermediate LM stenoses, by using intravascular ultrasound (IVUS) and fractional flow reserve (FFR) respectively, is crucial (1). However, increased left ventricular (LV) pressures might affect FFR measurements (2). Here we describe the case of a patient with chronic coronary syndrome and severe LV dysfunction in whom coronary angiography revealed an intermediate LM stenosis and catheterization identified an increased LV end-diastolic pressure. FFR measurement showed disproportionally higher FFR values compared with the minimal luminal area assessed by IVUS. When cardiac output was artificially augmented by using Impella for assisting percutaneous coronary intervention, the value of FFR measurement turned out proportional to what expected for the degree of anatomical stenosis. This discrepancy between anatomic and functional measurement may be a sign of coronary autoregulation dysfunction and therefore could help to identify high-risk patients in whom the use of a mechanical support device is more beneficial during percutaneous revascularization.

Safety and Efficacy of Selective, Clopidogrel-Based Strategies in Acute Coronary Syndrome: A Study-Level Meta-analysis.

OBJECTIVES: To investigate outcomes with selective, clopidogrel-based therapies versus conventional treatment in patients undergoing percutaneous coronary intervention (PCI), especially for acute coronary syndrome. BACKGROUND: Safety and efficacy of alternative, selective, clopidogrel-based therapies after PCI are not robustly established. METHODS: We performed a study-level meta-analysis on six randomized trials investigating selective clopidogrel-based therapies (three on unguided de-escalation, N = 3,473; three on guided clopidogrel therapy, N = 7,533). Control groups received ticagrelor or prasugrel treatment. Main endpoints were major bleeding, any bleeding, major adverse cardiovascular events (MACE), and net clinical endpoint. RESULTS: The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based therapy versus the conventional treatment arm (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51-1.01, p = 0.06; OR: 0.93, 0.72-1.20, p = 0.58; respectively). The rates of any bleeding were lower in the selective, clopidogrel-based therapy versus conventional treatment group (OR: 0.57, 95% CI: 0.40-0.80, p = 0.001); this greater safety was significant for unguided de-escalation (OR: 0.43, 95% CI: 0.32-0.58, p = 0.00001) and nonsignificant for guided clopidogrel therapy (OR: 0.72, 95% CI: 0.51-1.02, p = 0.07; p for interaction: 0.03). The incidence of the net clinical endpoint was fewer in the selective, clopidogrel-based therapy versus the conventional treatment arm (OR: 0.59, 95% CI: 0.41-0.85, p = 0.004); this benefit was significant for unguided de-escalation (OR: 0.50, 95% CI: 0.39-0.64, p < 0.00001) and nonsignificant for guided clopidogrel therapy (OR 0.85, 95% CI: 0.62-1.16, p = 0.30; p for interaction: 0.01). CONCLUSION: As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based approaches provide a similar protection from cardiovascular events, reduce the risk of any bleeding, and are associated with a greater net benefit. These beneficial effects were prevalent with unguided de-escalation to clopidogrel.

Predictors of Mortality and Cardiovascular Outcome at 6 Months after Hospitalization for COVID-19.

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01-1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05-6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19-10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13-8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered.

Safety and Efficacy of Different Antithrombotic Strategies after Transcatheter Aortic Valve Implantation: A Network Meta-Analysis.

BACKGROUND: The optimal pharmacological therapy after transcatheter aortic valve implantation (TAVI) remains uncertain. We compared efficacy and safety of various antiplatelet and anticoagulant approaches after TAVI by a network meta-analysis. METHODS: A total of 14 studies (both observational and randomized) were considered, with 24,119 patients included. Primary safety endpoint was the incidence of any bleeding complications during follow-up. Secondary safety endpoint was major bleeding. Efficacy endpoints were stroke, myocardial infarction, and cardiovascular mortality. A frequentist network meta-analysis was conducted with a random-effects model. The following strategies were compared: dual antiplatelet therapy (DAPT), single antiplatelet therapy (SAPT), oral anticoagulation (OAC), and OAC + SAPT. The mean follow-up was 15 months. RESULTS: In comparison to DAPT, SAPT was associated with a 44% risk reduction of any bleeding (odds ratio [OR]: 0.56 [95% confidence interval, CI: 0.39-0.80]). SAPT was ranked as the safest strategy for the prevention of any bleeding (p-score: 0.704), followed by OAC alone (p-score: 0.476) and DAPT (p-score: 0.437). Consistent results were observed for major bleeding. The incidence of cardiovascular death and secondary ischemic endpoints did not differ among the tested antithrombotic approaches. In patients with indication for long-term anticoagulation, OAC alone showed similar rates of stroke (OR: 0.92 [95% CI: 0.41-2.05], p = 0.83) and reduced occurrence of any bleeding (OR: 0.49 [95% CI: 0.37-0.66], p < 0.01) versus OAC + SAPT. CONCLUSION: The present network meta-analysis supports after TAVI the use of SAPT in patients without indication for OAC and OAC alone in those needing long-term anticoagulation.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study.

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Interaction between thrombin potential and age on early clinical outcome in patients hospitalized for COVID-19.

Patients with Coronavirus Disease-2019 (COVID-19) have haemostatic dysfunction and are at higher risk of thrombotic complications. Although age is a major risk factor for outcome impairment in COVID-19, its impact on coagulative patterns here is still unclear. We investigated the association of Endogenous Thrombin Potential (ETP) with thrombotic and haemorrhagic events according to different ages in patients admitted for COVID-19. A total of 27 patients with COVID-19-related pneumonia, without need for intensive care unit admission or mechanical ventilation at hospital presentation, and 24 controls with non-COVID-19 pneumonia were prospectively included. ETP levels were measured on admission. Patients were evaluated for major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke, transient ischemic attack, venous thromboembolism) and bleeding complications [according to Bleeding Academic Research Consortium (BARC) definition] during in-hospital stay. COVID-19 patients had similar ETP levels compared to controls (AUC 93 ± 24% vs 99 ± 21%, p = 0.339). In the COVID-19 cohort, patients with in-hospital MACE showed lower ETP levels on admission vs those without (AUC 86 ± 14% vs 95 ± 27%, p = 0.041), whereas ETP values were comparable in patients with or without bleeding (AUC 82 ± 16% vs 95 ± 26%, p = 0.337). An interaction between age and ETP levels for both MACE and bleeding complications was observed, where a younger age was associated with an inverse relationship between ETP values and adverse event risk (pint 0.018 for MACE and 0.050 for bleeding). Patients with COVID-19 have similar thrombin potential on admission compared to those with non-COVID-19 pneumonia. In younger COVID-19 patients, lower ETP levels were associated with a higher risk of both MACE and bleeding.

First-in-Man trial of a drug-free bioresorbable stent designed to minimize the duration of coronary artery scaffolding.

For the last two decades, various degradable stents have been proposed to treat coronary artery diseases and replace metallic stents to avoid residual foreign material after healing. To date, the right balance between suitable scaffolding and loss of radial strength soon after endothelium restoration is still an unmet need. The present article reports on the First-in-Man trial of a drug-free bioresorbable stent based on a lactic acid stereocopolymer composed of 98% l-lactyl units selected to release stress shielding earlier than in the case of homopoly(l-lactic acid). Thirty patients with single de novo coronary lesions were included in the trial. The fate of scaffolds was monitored by clinical and imaging follow-ups to assess rate of adverse events, acute recoil, late luminal loss, and late lumen recovery. There was no death, no myocardial infarction, and no stent thrombosis observed over the 36 months trial. Dismantling occurred about 3 months after implantation. Bioresorption was almost completed at 2 years. The late lumen loss observed at the end of the first year was partly compensated one year later by enlarging remodeling. At one year, a neointimal hyperplasia slightly greater than for drug-eluting metallic and bioresorbable stents was shown using optical coherence tomography. The excess of hyperplasia was discussed relative to struts thickness, absence of anti-proliferative drug, and release of degradation by-products.

Return towards normality in admissions for myocardial infarction after the lockdown removal for COVID-19 outbreak in Italy.

BACKGROUND: Investigations demonstrated a decrease of admissions for myocardial infarction (MI) during the CoronaVirus Disease-19 (COVID-19) outbreak. No study has evaluated the time required to reverse this downward curve of MI admissions. METHODS: This is a retrospective analysis on patients (N = 2415) admitted to the Emergency Departments for acute MI in nine Italian centers. Primary endpoint was the incidence rates (IRs) of MI admissions in the post-lockdown COVID-19 period (case-period: from May 4 to July 12, 2020) vs. the following control periods: January 1-February 19, 2020 (pre-lockdown period); February 20-May 3, 2020 (intra-lockdown period); May 4-July 12, 2019 (inter-year non-COVID-19 period). RESULTS: IR of admissions for MI in the post-lockdown period was higher than the intra-lockdown period (IR ratio, IRR: 1.60, 95% CI 1.42-1.81; p = 0.0001), was lower than the pre-lockdown period (IRR: 0.86, 0.77-0.96; p = 0.009) and similar to the inter-year non-COVID-19 period (IRR: 0.96, 0.87-1.07; p = 0.47). Within the case period, the increase in MI admissions was more pronounced in earlier vs later weeks (IRR 1.19, 95% CI 1.02-1.38, p = 0.024) and, compared to the inter-year control period, was significant for non ST-segment elevation MI (IRR: 1.25, 95% CI 1.08-1.46, p = 0.004), but was not observed for ST-segment elevation MI (STEMI), where hospitalizations were reduced (IRR 0.76, 95% CI 0.65-0.88, p = 0.0001). CONCLUSIONS: Our study first indicates an increase in the number of admissions for MI after the removal of the national lockdown for COVID-19 in Italy. This increase was prevalent in the first weeks following the lockdown removal, but was under-represented in STEMI patients.

Clinical outcome with different doses of low-molecular-weight heparin in patients hospitalized for COVID-19.

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study.

INTRODUCTION: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. METHODS: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. CONCLUSION: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.