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.
Coronavirus disease 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019 and spread rapidly around the world. Several patients with severe COVID-19 infection can ...develop a coagulopathy according to the ISTH criteria for disseminated intravascular coagulopathy (DIC) with fulminant activation of coagulation, resulting in widespread microvascular thrombosis and consumption of coagulation factors. We conducted a meta-analysis in order to explore differences in coagulopathy indices in patients with severe and non-severe COVID-19. An electronic search was performed within PubMed, Google Scholar and Scopus electronic databases between December 2019 (first confirmed Covid-19 case) up to April 6th, 2020. The primary endpoint was the difference of D-dimer values between Non-Severe vs Severe disease and Survivors vs Non-Survivors. Furthermore, results on additional coagulation parameters (platelet count, prothrombin time, activated partial thromboplastin time) were also analyzed. The primary analysis showed that mean d-dimer was significantly lower in COVID-19 patients with non-severe disease than in those with severe (SMD - 2.15 - 2.73 to - 1.56, I
98%, P < 0.0001). Similarly, we found a lower mean d-dimer in Survivors compared to Non-Survivors (SMD - 2.91 - 3.87 to - 1.96, I
98%, P < 0.0001). Additional analysis of platelet count showed higher levels of mean PLT in Non-Severe patients than those observed in the Severe group (SMD 0.77 0.32 to 1.22, I
96%, P < 0.001). Of note, a similar result was observed even when Survivors were compared to Non-Survivors (SMD 1.84 1.16 to 2.53, I
97%, P < 0.0001). Interestingly, shorter mean PT was found in both Non-Severe (SMD - 1.34 - 2.06 to - 0.62, I
98%, P < 0.0002) and Survivors groups (SMD - 1.61 - 2.69 to - 0.54, I
98%, P < 0.003) compared to Severe and Non-Survivor patients. In conclusion, the results of the present meta-analysis demonstrate that Severe COVID-19 infection is associated with higher D-dimer values, lower platelet count and prolonged PT. This data suggests a possible role of disseminated intravascular coagulation in the pathogenesis of COVID-19 disease complications.
Exosomal miRNAs in Heart Disease Iaconetti, Claudio; Sorrentino, Sabato; De Rosa, Salvatore ...
Physiology
31, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Micro-RNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression. Exosomes have recently emerged as novel elements of intercellular communication in the ...cardiovascular system. Exosomal miRNAs could be key players in intercellular cross-talk, particularly during different diseases such as myocardial infarction (MI) and heart failure (HF). This review addresses the functional role played by exosomal miRNAs in heart disease and their potential use as new biomarkers.
Empagliflozin showed efficacy in controlling glycaemia, leading to reductions in HbA1c levels, weight loss and blood pressure, compared to standard treatment. Moreover, the EMPA-REG OUTCOME trial ...demonstrated a 14% reduction of major adverse cardiovascular events (MACE), a 38% reduction in cardiovascular (CV) death and a 35% reduction in the hospitalization rate for heart failure (HF). These beneficial effect on HF were apparently independent from glucose control. However, no mechanistic in vivo studies are available to explain these results, yet. We aimed to determine the effect of empagliflozin on left ventricular (LV) function in a mouse model of doxorubicin-induced cardiomyopathy (DOX-HF).
Male C57Bl/6 mice were randomly assigned to the following groups: controls (CTRL, n = 7), doxorubicin (DOX, n = 14), DOX plus empagliflozin (DOX + EMPA, n = 14), or DOX plus furosemide (DOX + FURO group, n = 7). DOX was injected intraperitoneally. LV function was evaluated at baseline and after 6 weeks of treatment using high-resolution echocardiography with 2D speckle tracking (Vevo 2100). Histological assessment was obtained using Haematoxylin and Eosin and Masson's Goldner staining.
A significant decrease in both systolic and diastolic LV function was observed after 6 weeks of treatment with doxorubicin. EF dropped by 32% (p = 0.002), while the LS was reduced by 42% (p < 0.001) and the CS by 50% (p < 0.001). However, LV function was significantly better in the DOX + EMPA group, both in terms of EF (61.30 ± 11% vs. 49.24 ± 8%, p = 0.007), LS (- 17.52 ± 3% vs. - 13.93 ± 5%, p = 0.04) and CS (- 25.75 ± 6% vs. - 15.91 ± 6%, p < 0.001). Those results were not duplicated in the DOX + FURO group. Hearts from the DOX + EMPA group showed a 50% lower degree of myocardial fibrosis, compared to DOX mice (p = 0.03). No significant differences were found between the DOX + FURO and the DOX group (p = 0.103).
Empagliflozin attenuates the cardiotoxic effects exerted by doxorubicin on LV function and remodelling in nondiabetic mice, independently of glycaemic control. These findings support the design of clinical studies to assess their relevance in a clinical setting.
It remains unknown what percentage of patients treated with percutaneous coronary artery intervention (PCI) have high residual inflammatory risk (RIR). Moreover, the impact of RIR on clinical ...outcomes has not been established. The objective of this study is to determine the prevalence of patients with persistent high levels of inflammation after PCI and to evaluate clinical outcomes according to inflammatory response.
This is a retrospective cohort study assessing patients undergoing PCI between 2009 and 2016 with serial inflammatory status assessment from a large, prospective, and single-centre PCI registry. Assessment of inflammation status with at least two high sensitive C-reactive protein (hsCRP) measurements at baseline and follow-up with >4 weeks apart. High RIR was defined as an hsCRP≥ 2 mg/L. Patients were divided into four groups: persistent high RIR, increased RIR (first low-, then high hsCRP), attenuated RIR (first high-, then low hsCRP), or persistent low RIR. The primary endpoint was all-cause mortality at 1 year follow-up. Occurrence of myocardial infarction (MI) was assessed as secondary outcome. Seven thousand and twenty-six patients were identified with serial hsCRP measurements (30.8% of all PCI patients). Of these patients 2654 (38%) had persistent high RIR, 719 patients (10%) had increased RIR, 1088 patients (15%) had attenuated RIR, and persistent low RIR was seen in 2565 patients (37%). All-cause mortality at 1 year was 2.6% in patients with persistent high RIR, compared with 1.0% in increased RIR, 0.3% in attenuated RIR, and 0.7% in persistent low RIR patients, P < 0.01. MI at 1 year was observed in 7.5% of persistent high RIR, compared with 6.4% in increased RIR, 4.6% in attenuated RIR, and 4.3% in persistent low RIR, P < 0.01. In an adjusted model, including accounting for diabetes mellitus, acute coronary syndrome, and baseline low-density lipoprotein, results were sustained.
Persistent high RIR is observed frequently in patients undergoing PCI. In these patients, significantly higher all-cause mortality and MI rates are observed at 1 year follow-up. Residual inflammatory risk in patients undergoing PCI should be identified and treatment options should be further explored.
This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major ...hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22-23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides.
There is recent new evidence regarding the combined use of direct oral antiocoagulants and antiplatelet agents in patients with Atrial Fibrillation undergoing PCI. To compare the efficacy of dual ...antithrombotic treatment (DAT) including a direct oral anticoagulant (DOAC) and an antiplatelet agent versus triple antithrombotic treatment (TAT) with a vitamin K antagonist (VKA). PubMed, SCOPUS and Google Scholar from through 09/09/2019; references of eligible studies; relevant scientific sessions abstracts and cardiology websites. Compared TAT including a VKA, a therapeutic DAT regimen including a DOAC was associated with a significant reduction of the primary safety endpoint in AF patients undergoing PCI with stent implantation for an ACS or chronic coronary syndrome, while no significant difference was found in the rate of ischemic adverse events, including stroke, acute myocardial infarction or stent thrombosis.
During ischemia a close relationship exists between sub-endocardial blood flow and myocardial function. Strain parameters can capture an impairment of regional longitudinal function but are load ...dependent. Recently, a novel non-invasive method to calculate Myocardial Work (MW) showed a strong correlation with invasive work measurements. Our aim was to investigate the ability of non-invasive MW indices to identify the ischaemic risk area during transient acute coronary occlusion (TACO).
The study population comprises 50 individuals with critical coronary stenosis (CCS). Echocardiography recordings were obtained before coronary angiography, during TACO and after revascularization to measure global longitudinal strain (GLS), Myocardial Work Index (MWI), Myocardial Constructive Work (MCW), Myocardial Wasted work (MWW), Myocardial work efficiency (MWE). Compared to baseline, we found a significant reduction of GLS (p = 0.005), MWI, MCW and MWE (p<0.001) during TACO.
The non-invasive measurement of MW parameters is a sensitive and early marker of myocardial ischemia during TACO.
The aim of this study was to evaluate the long-term impact of coronary artery calcification (CAC) on outcomes after percutaneous coronary intervention and the respective performance of first- and ...second-generation drug-eluting stents (DES).
Whether contemporary DES have improved the long-term prognosis after percutaneous coronary intervention in lesions with severe CAC is unknown.
Individual patient data were pooled from 18 randomized trials evaluating DES, categorized according to the presence of angiography core laboratory–confirmed moderate or severe CAC. Major endpoints were the patient-oriented composite endpoint (death, myocardial infarction MI, or any revascularization) and the device-oriented composite endpoint of target lesion failure (cardiac death, target vessel MI, or ischemia-driven target lesion revascularization). Multivariate Cox proportional regression with study as a random effect was used to assess 5-year outcomes.
A total of 19,833 patients were included. Moderate or severe CAC was present in 1 or more target lesions in 6,211 patients (31.3%) and was associated with increased 5-year risk for the patient-oriented composite endpoint (adjusted hazard ratio adjHR: 1.12; 95% confidence interval CI: 1.05 to 1.20) and target lesion failure (adjHR: 1.21; 95% CI: 1.09 to 1.34), as well as death, MI, and ischemia-driven target lesion revascularization. In patients with CAC, use of second-generation DES compared with first-generation DES was associated with reductions in the 5-year risk for the patient-oriented composite endpoint (adjHR: 0.88; 95% CI: 0.78 to 1.00) and target lesion failure (adjHR: 0.73; 95% CI: 0.61 to 0.87), as well as death or MI, ischemia-driven target lesion revascularization, and stent thrombosis. The relative treatment effects of second-generation compared with first-generation DES were consistent in patients with and without moderate or severe CAC, although outcomes were consistently better with contemporary devices.
In this large-scale study, percutaneous coronary intervention of target lesion moderate or severe CAC was associated with adverse patient-oriented and device-oriented adverse outcomes at 5 years. These detrimental effects were mitigated with second-generation DES.
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Over the past two decades, transcatheter aortic valve replacement (TAVR) swiftly evolved from a disrupting technology towards mainstream therapy in the field of severe symptomatic aortic stenosis. A ...series of randomized evaluations established its role in treating severe aortic stenosis patients across all surgical risk categories, paving the way for an extension of its indications to younger low-risk patients with a longer life expectancy. Therefore, managing comorbidities and limiting procedural complications, which may affect long-term outcomes, is of paramount importance. Among those, new-onset conduction disturbances and concomitant coronary artery disease remain two of the most debated issues. In the present review, we will discuss the incidence, prognostic impact, and unmet needs of patients with post-TAVR new-onset conduction disturbances and the ongoing challenges posed by the management of concomitant coronary artery disease.
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