Predictors of a sudden cardiovascular death

Background and Objectives: The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes. Methods: Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel. Results: Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men. Conclusion: In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.

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Cardiovascular Disease in Spondyloarthritides

Current Vascular Pharmacology ◽

10.2174/1570161117666190426164306 ◽

2020 ◽

Vol 18 (5) ◽

pp. 473-487 ◽

Cited By ~ 4

Author(s):

Charalampos Papagoras ◽

Paraskevi V. Voulgari ◽

Alexandros A. Drosos

Keyword(s):

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Healthcare Providers ◽

Cardiovascular Death ◽

Point Of View ◽

Treat To Target ◽

Inflammatory Joint Diseases ◽

Scientific Organizations ◽

Increased Risk ◽

Risk Patients

The spondyloarthritides are a group of chronic systemic inflammatory joint diseases, the main types being ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Evidence accumulating during the last decades suggests that patients with AS or PsA carry an increased risk for cardiovascular disease and cardiovascular death. This risk appears to be mediated by systemic inflammation over and above classical cardiovascular risk factors. The excess cardiovascular risk in those patients has been formally acknowledged by scientific organizations, which have called physicians’ attention to the matter. The application by Rheumatologists of new effective anti-rheumatic treatments and treat-to-target strategies seems to benefit patients from a cardiovascular point of view, as well. However, more data are needed in order to verify whether anti-rheumatic treatments do have an effect on cardiovascular risk and whether there are differences among them in this regard. Most importantly, a higher level of awareness of the cardiovascular risk is needed among patients and healthcare providers, better tools to recognize at-risk patients and, ultimately, commitment to address in parallel both the musculoskeletal and the cardiovascular aspect of the disease.

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Predictors of outcomes in patients with mitral regurgitation undergoing percutaneous valve repair

European Heart Journal ◽

10.1093/ehjci/ehaa946.2008 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Polimeni

Keyword(s):

Heart Failure ◽

Mitral Valve ◽

Mitral Regurgitation ◽

Primary Endpoint ◽

Cardiovascular Death ◽

Volume Index ◽

Valve Repair ◽

Percutaneous Valve Repair ◽

Percutaneous Valve

Abstract Background Percutaneous mitral valve repairs has been increasingly performed worldwide. The MITRA-UMG registry provides a snapshot of a real-world clinical data and outcomes. Purpose We sought to investigate predictors of clinical outcomes in patients with mitral regurgitation undergoing percutaneous valve repair. Methods The MITRA-UMG registry retrospectively collected data from consecutive patients with symptomatic moderate-to-severe or severe MR underwent MitraClip implantation. The primary endpoint of interest was the composite of cardiovascular death or rehospitalization for HF. Results Between March 2012 and July 2018, a total of 133 consecutive patients admitted to our institution were included. Acute procedural success was obtained in 95.4% of patients, with no intraprocedural death. The composite primary endpoint of cardiovascular death or rehospitalization for heart failure was met in 50 patients (38%) with cumulative incidences of 7%, 25%, at 30 days and 1 year, respectively. In the Cox multivariate model, NYHA functional class IV, left ventricular end-diastolic volume index (LVEDVi), Euroscore II, independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan-Meier analysis, a LVEDVi >92 ml/m2 was associated with an increased incidence of the primary endpoint. Conclusions In searching the ideal phenotype of patients who benefit most of percutaneous mitral valve repair, those presenting with severely dilated ventricles (LVEDVi >92 ml/m2), high operative risk (EUROSCORE II >7%) or advanced heart failure symptoms (NYHA IV) at baseline carried the worst prognosis at long-term. Funding Acknowledgement Type of funding source: None

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S62798, a TAFIa inhibitor, accelerates endogenous thrombolysis in a murine model of pulmonary thromboembolism

European Heart Journal ◽

10.1093/ehjci/ehaa946.3361 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Sansilvestri-Morel ◽

F Bertin ◽

I Lapret ◽

B Neau ◽

V Blanc-Guillemaud ◽

...

Keyword(s):

Pulmonary Thromboembolism ◽

Prediction Interval ◽

Therapeutic Option ◽

Geometric Mean ◽

Active Form ◽

Cardiovascular Death ◽

Vehicle Group ◽

Fibrin Deposition ◽

Minimal Effective Dose ◽

Endogenous Fibrinolysis

Abstract Pulmonary embolism (PE) is the third leading cause of cardiovascular death in western countries. The enhancement of fibrinolysis constitutes a promising approach to treat thrombotic diseases. In patients, venous thrombosis and thromboembolism risks are associated with increased plasma levels of TAFI (Thrombin Activatable Fibrinolysis Inhibitor) antigen as well as the active form TAFIa. S62798 is a competitive, selective and potent human TAFIa inhibitor (IC50±SD=11.2±0.4nM). It is however less potent on mouse TAFIa (IC50±SD=270±39nM). Here, we tested the ability of S62798 to enhance endogenous fibrinolysis in a mouse model of pulmonary thromboembolism. Human Tissue Factor (TF) was injected in C57Bl6 male mice. Ten minutes later, mice (n=4 to 14 per group) were treated (IV) with S62798 (from 0.01 to 100mg/kg) or vehicle (0.9% NaCl). Ten or twenty minutes (min) later, mice were anesthetized and lungs were collected, homogenized and pulmonary fibrin was quantified by ELISA. Results are expressed as ratio of geometric mean of pulmonary fibrin (μg/mL): tested treatment/ vehicle [95% confidence interval (CI)]. Ten minutes after S62798 treatment, pulmonary fibrin deposition was dose-dependently decreased with a Minimal Effective Dose of 0.04mg/kg [90% prediction interval 0.037 - 0.051] and an ED50 of 0.03mg/kg [95% CI: 0.01; 0.06]. Mice were then treated with 0.1mg/kg S62798 or vehicle (10 min after TF induction) and fibrin deposition in lungs was quantified 10 and 20 minutes post S62798 treatment. The level of pulmonary fibrin deposition was significantly decreased (p<0.0001) compared to vehicle group (ratio 0.31 [0.21; 0.45] at 10 min; 0.35 [0.24; 0.51] at 20 min). Finally, the effect of S62798 (1mg/kg) in combination with heparin was evaluated (n=10/group). When administered 10 min before TF injection, heparin (2000IU/kg) significantly (p<0.0001) decreased pulmonary fibrin level (20 min post TF: ratio 0.03 [0.01; 0.05]). When treatment was done in a curative setting (10 min post TF), heparin alone had no effect (p=0.85) on fibrin deposition (ratio 0.96 [0.65; 1.43]) whereas a similar significant (p<0.0001) decreased pulmonary fibrin deposition was observed in response to S62798 alone or associated with heparin (ratio 0.27 [0.18; 0.40] (S62798 alone) and 0.29 [0.20; 0.43] (S62798+heparin)). In this model, curative S62798 treatment, alone or associated to heparin, accelerated clot degradation by potentiating endogenous fibrinolysis and thus decreased pulmonary fibrin deposition. Due to its capacity to enhance endogenous fibrinolysis, S62798, which has completed phase I studies, is expected to be a therapeutic option for intermediate high risk PE patients on top of anticoagulants. With early recanalization, S62798 should rapidly reduce pulmonary artery pressure and resistance, with concomitant improvement in right ventricular function, preserving cardiac function, and reducing acute PE-related morbidity and mortality in these patients. Funding Acknowledgement Type of funding source: None

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Cardiovascular consequences of discontinuing low-dose rivaroxaban in people with chronic coronary or peripheral artery disease

Heart ◽

10.1136/heartjnl-2020-318758 ◽

2021 ◽

pp. heartjnl-2020-318758

Author(s):

Gilles R Dagenais ◽

Leanne Dyal ◽

Jacqueline J Bosch ◽

Darryl P Leong ◽

Victor Aboyans ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Low Dose ◽

Cardiovascular Death ◽

Stroke Rate ◽

Early Stopping ◽

Peripheral Artery ◽

Once Daily ◽

Registration Number ◽

Artery Disease

ObjectiveIn patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping.MethodsIncident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068).ResultsDuring randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin.ConclusionDiscontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess.Trial registration numberNCT01776424.

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