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.
Transcatheter left atrial appendage (LAA) occlusion is an alternative strategy for stroke prevention in patients with atrial fibrillation (AF).
This study sought to determine the incidence, ...predictors, and prognosis of thrombus formation on devices in patients with AF who were treated with LAA closure.
The study retrospectively analyzed data from patients treated with 2 LAA closure devices seen in 8 centers in France from February 2012 to January 2017.
A total of 469 consecutive patients with AF underwent LAA closure (272 Watchman devices Atritech, Boston Scientific, Natick, Massachusetts and 197 Amplatzer devices St. Jude Medical, Minneapolis, Minnesota). Mean follow-up was 13 ± 13 months, during which 339 (72.3%) patients underwent LAA imaging at least once. There were 98 major adverse events (26 thrombi on devices, 19 ischemic strokes, 2 transient ischemic attacks, 18 major hemorrhages, 33 deaths) recorded in 89 patients. The incidence of device-related thrombus in patients with LAA imaging was 7.2% per year. Older age (hazard ratio HR: 1.07 per 1-year increase; 95% confidence interval CI: 1.01 to 1.14; p = 0.02) and history of stroke (HR: 3.68; 95% CI: 1.17 to 11.62; p = 0.03) were predictors of thrombus formation on the devices, whereas dual antiplatelet therapy (HR: 0.10; 95% CI: 0.01 to 0.76; p = 0.03) and oral anticoagulation at discharge (HR: 0.26; 95% CI: 0.09 to 0.77; p = 0.02) were protective factors. Thrombus on the device (HR: 4.39; 95% CI: 1.05 to 18.43; p = 0.04) and vascular disease (HR: 5.03; 95% CI: 1.39 to 18.23; p = 0.01) were independent predictors of ischemic strokes and transient ischemic attacks during follow-up.
Thrombus formation on the device is not uncommon in patients with AF who are treated by LAA closure. Such events are strongly associated with a higher risk of ischemic stroke during follow-up. (REgistry on Real-Life EXperience With Left Atrial Appendage Occlusion RELEXAO; NCT03279406)
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Advances in antiplatelet therapies for patients with cardiovascular disease have improved patient outcomes over time, but the challenge of balancing the risks of ischaemia and bleeding remains ...substantial. Moreover, many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. Therefore, novel strategies are needed to prevent clinical events through mechanisms beyond platelet inhibition and with an acceptable associated risk of bleeding. The advent of non-vitamin K antagonist oral anticoagulants, which attenuate fibrin formation by selective inhibition of factor Xa or thrombin, has renewed the interest in dual-pathway inhibition strategies that combine an antiplatelet agent with an anticoagulant drug. In this Review, we highlight the emerging pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with different manifestations of cardiovascular disease, such as coronary artery disease, cerebrovascular disease and peripheral artery disease.
The effect of low-density lipoprotein cholesterol-lowering therapy with alirocumab or evolocumab on individual clinical efficacy and safety endpoints remains unclear. We aimed to evaluate the ...efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or atherosclerotic cardiovascular disease.
We performed a review of randomized controlled trials (RCTs) comparing treatment with alirocumab or evolocumab vs. placebo or other lipid-lowering therapies up to March 2018. Primary efficacy endpoints were all-cause death, cardiovascular death, myocardial infarction (MI), and stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included 39 RCTs comprising 66 478 patients of whom 35 896 were treated with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (14 639 with alirocumab and 21 257 with evolocumab) and 30 582 with controls. Mean weighted follow-up time across trials was 2.3 years with an exposure time of 150 617 patient-years. Overall, the effects of PCSK9 inhibition on all-cause death and cardiovascular death were not statistically significant (P = 0.15 and P = 0.34, respectively). Proprotein convertase subtilisin-kexin type 9 inhibitors were associated with lower risk of MI (1.49 vs. 1.93 per 100 patient-year; RR 0.80, 95% CI 0.74-0.86; I 2 = 0%; P < 0.0001), ischaemic stroke (0.44 vs. 0.58 per 100 patient-year; RR 0.78, 95% CI 0.67-0.89; I 2 = 0%; P = 0.0005), and coronary revascularization (2.16 vs. 2.64 per 100 patient-year; RR 0.83, 95% CI 0.78-0.89; I 2 = 0%; P < 0.0001), compared with the control group. Use of these PCSK9 inhibitors was not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97).
Proprotein convertase subtilisin-kexin type 9 inhibition with alirocumab or evolocumab was associated with lower risk of MI, stroke, and coronary revascularization, with favourable safety profile.
Objectives We sought to analyze the composition of coronary thrombus in vivo in ST-segment elevation myocardial infarction (STEMI) patients. Background The dynamic process of intracoronary thrombus ...formation in STEMI patients is poorly understood. Methods Intracoronary thrombi (n = 45) were obtained by thromboaspiration in 288 consecutive STEMI patients presenting for primary percutaneous intervention, and analyzed using high-definition pictures taken with a scanning electron microscope. Plasma biomarkers (TnI, CRPus, IL-6, PAI-1, sCD40 ligand, and TNF-α) and plasma fibrin clot viscoelastic properties were measured simultaneously on peripheral blood. Results Thrombi were mainly composed of fibrin (55.9 ± 18%) with platelets (16.8 ± 18%), erythrocytes (11.5 ± 9%), cholesterol crystals (5.2 ± 8.4%), and leukocytes (1.3 ± 2.0%). The median ischemic time was 175 min (interquartile range: 140 to 297). Ischemic time impacted thrombi composition, resulting in a positive correlation with intracoronary thrombus fibrin content, r = 0.38, p = 0.01, and a negative correlation with platelet content, r = −0.34, p = 0.02. Thus, fibrin content increased with ischemic time, ranging from 48.4 ± 21% (<3 h) up to 66.9 ± 9% (>6 h) (p = 0.02), whereas platelet content decreased from 24.9 ± 23% (<3 h) to 9.1 ± 6% (>6 h) (p = 0.07). Soluble CD40 ligand was positively correlated to platelet content in the thrombus (r = 0.40, p = 0.02) and negatively correlated with fibrin content (r = −0.36; p = 0.04). Multivariate analysis indicated that ischemic time was the only predictor of thrombus composition, with a 2-fold increase of fibrin content per ischemic hour (adjusted odds ratio: 2.00 95% confidence interval: 1.03 to 3.7; p = 0.01). Conclusions In acute STEMI, platelet and fibrin contents of the occlusive thrombus are highly dependent on ischemia time, which may have a direct impact on the efficacy of drugs or devices used for coronary reperfusion.
In a randomized trial involving patients with high-risk vascular disease, the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers but was ...not associated with a lower rate of cardiovascular events than placebo.
Pharmacologic reduction of the low-density lipoprotein (LDL) cholesterol level with statins substantially decreases the risks of death and complications from cardiovascular causes.
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Considerable interest has focused on the identification of approaches that might further reduce cardiovascular-event rates among high-risk patients.
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Epidemiologic studies have shown inverse associations between high-density lipoprotein (HDL) cholesterol levels and cardiovascular outcomes,
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a correlation that persists despite treatment with statins.
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Nevertheless, therapeutic interventions that raise the HDL cholesterol level have not been shown to reduce cardiovascular risk.
Cholesteryl ester transfer protein (CETP) modulates the transfer of esterified cholesterol from HDL to apolipoprotein B–containing lipoproteins.
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Two . . .
In this trial, bedside platelet-function monitoring to adjust antiplatelet therapy after coronary stent implantation did not reduce the rate of subsequent cardiovascular events, a finding that calls ...into question the clinical value of this type of testing.
Clopidogrel and aspirin play a central role in the treatment of patients undergoing percutaneous coronary intervention.
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Up to one third of patients have inadequate platelet inhibition, with an increased risk of events.
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Platelet-function testing can determine the degree of platelet reactivity during treatment at the bedside and potentially identify patients in whom adjustment of antiplatelet therapy is warranted to minimize the risks of both ischemic and bleeding complications.
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Cohort studies and meta-analyses have largely shown the prognostic value of high platelet reactivity during antiplatelet therapy in patients undergoing coronary stenting.
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Randomized clinical trials have also shown that stronger . . .
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inhibitors are effective in non–ST-segment elevation acute coronary syndromes, but the timing of drug dosing is unclear. In this trial, pretreatment with prasugrel, as compared with treatment ...after coronary angiography, did not improve outcomes and increased the risk of bleeding.
Clopidogrel does not become biologically and clinically effective until several hours after administration.
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Although a loading dose of clopidogrel is required in patients undergoing percutaneous coronary intervention (PCI), it is uncertain whether pretreatment with clopidogrel (with treatment given early enough before catheterization to be effective) is efficient when the coronary-artery anatomy in a patient with a non–ST-segment elevation (NSTE) acute coronary syndrome is not known. Pretreatment can delay a coronary-artery bypass grafting (CABG) procedure or increase unnecessarily the risk of bleeding in patients who do not need to undergo PCI. Two randomized studies, one involving patients with NSTE acute . . .
Summary Background Elderly patients are at high risk of ischaemic and bleeding events. Platelet function monitoring offers the possibility to individualise antiplatelet therapy to improve the ...therapeutic risk–benefit ratio. We aimed to assess the effect of platelet function monitoring with treatment adjustment in elderly patients stented for an acute coronary syndrome. Methods We did this multicentre, open-label, blinded-endpoint, randomised controlled superiority study at 35 centres in France. Patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome were randomly assigned (1:1), via a central interactive voice-response system based on a computer-generated permuted-block randomisation schedule with randomly selected block sizes, to receive oral prasugrel 5 mg daily with dose or drug adjustment in case of inadequate response (monitoring group) or oral prasugrel 5 mg daily with no monitoring or treatment adjustment (conventional group). Randomisation was stratified by centre. Platelet function testing was done 14 days after randomisation and repeated 14 days after treatment adjustment in patients in the monitoring group. Study investigators and patients were not masked to treatment allocation, but allocation was concealed from an independent clinical events committee responsible for endpoint adjudication. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, and Bleeding Academic Research Consortium-defined bleeding complications (types 2, 3, or 5) at 12 months' follow-up. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01538446. Findings Between March 27, 2012, and May 19, 2015, we randomly assigned 877 patients to the monitoring group (n=442) or the conventional group (n=435). The primary endpoint occurred in 120 (28%) patients in the monitoring group compared with 123 (28%) patients in the conventional group (hazard ratio HR, 1·003, 95% CI 0·78–1·29; p=0·98). Rates of bleeding events did not differ significantly between groups. Interpretation Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations. Funding Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.
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