Anticoagulation In Pulmonary Arterial Hypertension Research Articles

Anticoagulation in pulmonary arterial hypertension - association with mortality, healthcare utilization, and quality of life: The Pulmonary Hypertension Association Registry (PHAR).

Routine long-term anticoagulation in pulmonary arterial hypertension (PAH) is controversial. To date, anticoagulation has been found to be beneficial or neutral in idiopathic disease (IPAH) and neutral-to-harmful in connective tissue disease (CTD-PAH). We sought to examine the association between anticoagulation and mortality, healthcare utilization, and quality of life (QoL) in PAH. The PHAR is a prospective registry of PAH patients referred to 58 pulmonary hypertension care centers in the United States. We compared patients who received anticoagulation during enrollment (questionnaire documented) to those who did not. Cox proportional hazard models were used for mortality, Poisson multivariate regression models for healthcare utilization, and generalized estimating equations for QOL RESULTS: Of 1175 patients included, 316 patients were treated with anticoagulation. IPAH/hereditary PAH (HPAH) comprised 46% of the cohort and CTD-PAH comprised 33%. After adjustment for demographics, clinical characteristics, site and disease severity, anticoagulation was not associated with mortality in the overall population (HR, 1.00; 95% CI, 0.72-1.36), IPAH/HPAH (HR, 1.19; 95% CI, 0.74-1.94), or CTD-PAH (HR 0.87; 95% CI, 0.53-1.42). Anticoagulation was associated with an increased rate of emergency department visits (IRR: 1.41), hospitalizations (IRR: 1.30), and hospital days (IRR 1.33). QOL measured by emPHasis-10 score was worse in patients receiving anticoagulation (mean difference 1.74; 95% CI 0.40-3.09). Anticoagulation is not associated with higher mortality, but is associated with increased healthcare utilization in the PHAR. PAH-specific QoL may be worse in patients receiving anticoagulation. The risks and benefits surrounding routine prescription of anticoagulation for PAH should be carefully considered.

PHYSICIANS ATTITUDES TOWARD ANTICOAGULATION USE IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The benefit of anticoagulant use in pulmonary arterial hypertension (PAH) patients remains unclear. Multiple studies have shown conflicting results regarding the utility of anticoagulation in PAH. Moreover, other points of controversies include selection of specific anticoagulant agent, intensity of anticoagulation, and patient selection based on PAH subtype. This study aims to evaluate the practice habits of physicians caring for patients with PAH in the United States of America (USA). METHODS: A seven-question web-based survey regarding anticoagulation management in patients with PAH in the USA was distributed by email to clinicians with experience treating patients with pulmonary hypertension and are registered members of the Pulmonary Hypertension Association (PHA). RESULTS: We received a total of 56 responses, predominantly from academic, non-profit institutions (82.14%, n=46); by PHA members serving as non-trainee physicians (98.21%, n=55). The majority of respondents (53.57%, n=31) rarely start anticoagulation in patients with WHO group 1 PAH. In idiopathic PAH (IPAH) subtype, providers mainly start in severe disease (22.82%, n=12) or for other coexisting indications (e.g., an indwelling catheter, underlying thrombogenic disorder, prior clots). Nearly all (86%, n=50) respondents rarely start anticoagulation in connective tissue disease related PAH (CTD-PAH). While the majority of respondents do not routinely use anticoagulation in general, those who do, use warfarin (46.3%, n=25) and target a lower range of INR (1.5–2). Few providers (18.18%, n=10) reported using direct oral anticoagulants. CONCLUSIONS: Despite the presence of limited evidence showing that the use of anticoagulation in patients with PAH may be associated with survival benefit—specifically in the idiopathic PAH subtype—the majority of clinicians who care for these patients believe that the risks outweigh the benefits unless there is a coexisting indication. Prospective and randomized studies are warranted for further evaluation. CLINICAL IMPLICATIONS: This study highlights the uncertainty among clinicians about the benefit of anticoagulation in patients with WHO group 1 PAH and the need for randomized trials. DISCLOSURES: No relevant relationships by Noura Alturaif, source=Web Response No relevant relationships by Jamie Kennedy, source=Web Response No relevant relationships by Sula Mazimba, source=Web Response Clinical Trial support relationship with Complexa, Inc Please note: $1001 - $5000 Added 04/02/2020 by Andrew Mihalek, source=Web Response, value=Grant/Research Support

Anticoagulation in pulmonary arterial hypertension: a decision analysis.

Systemic anticoagulation may be beneficial in pulmonary arterial hypertension, but there is no randomized clinical trial data to guide therapeutic decision making, and current guidelines do not account for patient preferences or quality of life. Decision analytic models to evaluate the potential risks and benefits of systemic anticoagulation in pulmonary arterial hypertension patients, focusing on the benefit in quality-adjusted life years, may be helpful in clarifying this uncertainty. We constructed a 31-state Markov decision analytic model to explore anticoagulation and no anticoagulation strategies. Modeled patient characteristics included gender, use of central catheter-based pulmonary arterial hypertension therapy, type of pulmonary arterial hypertension (idiopathic, idiopathic pulmonary arterial hypertension, or connective-tissue associated, connective tissue disease-pulmonary arterial hypertension), and use of oral contraceptive medication by females. Modeled events included mortality, thromboembolic complications, atrial fibrillation, stroke, and anticoagulation bleeding. Deterministic and probabilistic sensitivity analyses were performed. Anticoagulation was favored in all idiopathic pulmonary arterial hypertension cases, with a gain of 0.43–0.51 quality-adjusted life years, and detrimental in all connective tissue disease-pulmonary arterial hypertension cases, with a loss of 0.66–1.89 quality-adjusted life years. Anticoagulation would need to demonstrate a hazard ratio for pulmonary arterial hypertension mortality of 0.95 or better to be favored. In our model, idiopathic pulmonary arterial hypertension patients benefit from anticoagulation in terms of quality-adjusted life years, and connective tissue disease-pulmonary arterial hypertension patients were harmed, with a hazard ratio for pulmonary arterial hypertension mortality of 0.95 or better being required to favorably impact quality-adjusted life years. These results suggest that anticoagulation significantly improves quality adjusted life years and should be offered to all idiopathic pulmonary arterial hypertension patients. Shared decision models based on these results may help clarify therapeutic decision-making uncertainty in pulmonary arterial hypertension patients.

Is Anticoagulation Beneficial in Pulmonary Arterial Hypertension?

Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are inconsistent. The objective of this study was to examine the impact of adjunctive oral anticoagulants in patients with PAH through meta-analysis, and to further assess whether response differs by PAH subtype. Methods and Results Cochrane CENTRAL, Medline, and Scopus databases were searched for randomized or nonrandomized studies that assessed the association between anticoagulation and outcomes in patients with PAH. Hazard ratios (HRs) for mortality were pooled using the random effects model. Subgroup analyses were performed for type of PAH and study design. Twelve nonrandomized studies, at moderate risk of bias, were included. These consisted of 2512 patients (1342 receiving anticoagulation and 1170 controls). Anticoagulation significantly reduced mortality in the overall PAH cohort (HR, 0.73 [0.57, 0.93]; P=0.001; I2=64%). On subgroup analysis, a significant mortality reduction was seen in idiopathic PAH patients (HR, 0.73 [0.56, 0.95]; P=0.02; I2=46%), whereas no significant difference was observed in connective tissue disease-related PAH (HR, 1.16 [0.58, 2.32]; P=0.67; I2=71%). Sensitivity analysis specific to scleroderma-associated PAH demonstrated a significant increase in mortality with anticoagulant use (HR, 1.58 [1.08, 2.31]; P=0.02; I2=9%). Conclusions This meta-analysis shows that use of anticoagulation may improve survival in idiopathic PAH patients, while increasing mortality when used in scleroderma-associated-PAH patients. Currently, no randomized clinical trials have been published, and until randomized data are available, anticoagulant use in PAH should be tailored to PAH subtype.

Overdue to understand anticoagulation in pulmonary arterial hypertension.

Overdue to understand anticoagulation in pulmonary arterial hypertension.

Anti-coagulation in pulmonary arterial hypertension: the real blood and guts.

We read with interest the “Perspective” by Cirulis et al . and the accompanying editorial by Pakshirajan, both of which discuss our recent publication analyzing the effect of anticoagulation with warfarin in patients with pulmonary arterial hypertension (PAH) enrolled in the REVEAL registry (1).

Where do we go from here? Reappraising the data on anticoagulation in pulmonary arterial hypertension.

The use of anticoagulation as part of the treatment regimen in pulmonary arterial hypertension (PAH) remains a topic of debate. A recently published analysis of anticoagulation use in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) study offers conflicting conclusions regarding the benefit of this therapeutic strategy. There remains no robust randomized trial in PAH weighing the risks versus benefits of including anticoagulation in treatment regimens, leaving clinicians to surmise value in individual patients. Reexamination of available data may help to provide guidance on this controversial topic in the absence of future dedicated investigations.

Anticoagulation in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH.

Anticoagulation in patients with pulmonary arterial hypertension: An update on current knowledge

Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk.

Effect of Long-term Oral Anticoagulation in Pulmonary Arterial Hypertension (PAH)

Effect of Long-term Oral Anticoagulation in Pulmonary Arterial Hypertension (PAH)

Anticoagulation in pulmonary arterial hypertension: Contemporary data from COMPERA registry.

The use of anticoagulant therapy in patients with pulmonary arterial hypertension (PAH) has been controversial for decades. Recommendations for anticoagulation in these patients are often derived from small, retrospective, and single centre studies without any placebo-controlled randomized study. Furthermore, uncertainties exist regarding a number of issues such as patient selection, risk stratification for bleeding, the intensity of anticoagulation, appropriateness of anticoagulation in different types of PAH, and the potential use of new oral anticoagulants.Recently, the database of the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) has been analyzed to assess the effect of anticoagulation on the long-term outcome of patients with various forms of PAH. This analysis is the largest to date to assess anticoagulant therapy in PAH patients in a prospective design with long observation period. The results of COMPERA lend support to current recommendations for the use of anticoagulant therapy in patients with idiopathic PAH, but not in other forms of PAH. Also, the study confirmed the previously reported concern that anticoagulant therapy may be harmful in patients with scleroderma-associated PAH.

Antikoagulation bei pulmonal arterieller Hypertonie

In pulmonary arterial hypertension (PAH), thrombosis and thromboembolism occurs as a consequence of pulmonary microvasculopathy with a change of pulmonary vascular microenviroment toward a procoagulant, prothrombotic and antifibrinolytic pattern. Circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and prothrombotic cytokines have been identified in PAH patients so far. Thrombogenic pulmonary vasculopathy has been documented in many patients with PAH. Furthermore, most patients will not be diagnosed until right heart enlargement and impaired right ventricular function has developed. Thus, there is clear rationale for a treatment with anticoagulation. In four uncontrolled studies Warfarin improved the prognosis of patients with idiopathic and other forms of PAH. However, so far there are no prospective randomised studies evaluating the role of anticoagulants in the treatment of PAH. This review summarizes the current data and guidelines concerning anticoagulation in PAH.

Anticoagulation in pulmonary arterial hypertension: a qualitative systematic review

Thrombotic arteriopathy has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, the role of anticoagulants in the treatment of PAH is uncertain. Through a qualitative systematic review of epidemiological studies, the effectiveness of anticoagulation therapy with warfarin on survival was evaluated in patients with PAH. MEDLINE (1966 to November 2005), EMBASE (1966 to November 2005), bibliographies of included studies and published reviews were searched without language restriction. Epidemiological studies evaluating the effectiveness of warfarin in PAH were included. Studies had to report mortality as an outcome. Seven observational studies evaluating the effectiveness of warfarin comprising 488 patients were identified. Five studies support the effectiveness of anticoagulation therapy, whereas two do not. Data from observational studies suggest that anticoagulation therapy may be an effective intervention in pulmonary arterial hypertension. However, given the methodological limitations and the small number of existing observational studies, a randomised controlled trial is needed in order to definitively address this important clinical issue.

Early statin treatment following acute myocardial infarction and 1-year survival

The shear stress and hypoxia in the pulmonary artery in patients with pulmonary arterial hypertension(PAH) causes endothelial dysfunction, smooth muscle proliferation and activation of thrombotic pathways leading to in situ thrombosis. Targeting the thrombotic pathways is a proposed mechanism to slow disease progression and improve survival. Over the years, the survival in patients with PAH has improved due to multiple factors with the increased use of anticoagulation as one of them. Both European Respiratory Society/European Society of Cardiology and American College of Cardiology/American Heart Association guidelines make grade II recommendations for using anticoagulation in PAH. The guidelines are based on weak observational studies with high risk of bias which have only studied warfarin as the choice of anticoagulation. In this article, we review the pathophysiology, rationale and the current literature investigating the role of anticoagulation in PAH.