The Effect of Anticoagulant Therapy in Primary and Anorectic Drug-Induced Pulmonary Hypertension

Frank, Herbert; Mlczoch, J; Huber, Kurt; Schuster, Ernst; Gurtner, H. P.; Kneußl, Meinhard

doi:10.1378/chest.112.3.714

Cited by 227 publications

(135 citation statements)

References 25 publications

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“…The earliest studies of PAH showed that increased right atrial (RA) pressure, decreased CI, and increased mean pulmonary artery (PA) pressure were predictors of death or lung transplantation [28][29][30][31][32]. While these findings were published in an era before effective therapy was available, they have generally (but not universally) been validated in more recent studies of patients at diagnosis or initiation of therapy [19,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. Importantly, PAH patients with more severe cardiac dysfunction or history of heart failure at baseline continue to have a higher risk of death than those with less severe heart failure despite treatment with new therapies [33,34,36,38,41,45,46,48,49].…”

Section: Potential Surrogate and Intermediate End Points In Pah Hemodmentioning

confidence: 99%

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Snow¹,

Kawut²

2007

Clinics in Chest Medicine

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Pulmonary arterial hypertension (PAH) is a rare disease which is characterized by increased pulmonary vascular resistance and right heart failure. Recent discoveries in disease pathophysiology have been translated into effective therapies tested in clinical trials. The studies which have led to the regulatory board approval of therapies for PAH have focused on surrogate and intermediate end points, thought to reflect quantity and quality of life, respectively. However, validation of many of these surrogates is incomplete. It is also unknown which indicators of function or long-term survival should be used to formulate decisions regarding addition, discontinuation, or combination of therapies. Identification of suitable end points would therefore not only help investigators design appropriate clinical trials, but also assist clinicians in caring for patients with PAH. Hemodynamic, cardiac imaging, plasma biomarkers, and exercise testing hold some promise as potential surrogate end points for PAH. Functional status and quality of life assessments may also have important roles. Future studies should validate the most promising surrogate markers, so that patients, clinicians, subjects, and investigators may benefit from the advantages they confer on clinical care and on clinical trials.The past several years have yielded an explosion of randomized clinical trials (RCTs) of several new medical therapies for pulmonary arterial hypertension (PAH). The hopes for these and all treatments for potentially fatal diseases are 1) to improve how a patient feels or functions and/ or 2) to prolong survival. While simply stated, the assessment of progress towards these goals may be quite complex [1][2][3][4][5][6].New PAH therapies have gained regulatory board approval based on studies with intermediate and surrogate end points as primary outcomes, believed to reflect the impact of these drugs on quality of life (QOL) and survival, respectively. While hemodynamic, plasma, cardiac imaging, exercise, functional, and QOL parameters are promising candidates, the reliability and validity of these measures are not clearly established. In addition, there are no RCTs addressing the use of such end points in guiding management decisions in PAH, such as changing, intensifying, escalating, or combining therapies. Despite this lack of evidence, clinicians who

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Section: Potential Surrogate and Intermediate End Points In Pah Hemodmentioning

confidence: 99%

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Snow¹,

Kawut²

2007

Clinics in Chest Medicine

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“…In addition to rationale based on the pathobiology of pulmonary vascular disease, rationale for anticoagulation in patients with PH associated with heart disease is based on retrospective analyses from 7 studies in patients with idiopathic, heritable, or anorexigen-associated pulmonary arterial hypertension (formerly called primary PH), of which 5 were positive and 2 were negative. [685][686][687][688] By definition, pulmonary arterial hypertension (PAH; formerly called pulmonary vascular obstructive disease; recent classification, PH group I PAH) is an increased mean pulmonary artery pressure ≥25 mm Hg at rest, with a concomitant mean pulmonary capillary wedge pressure, mean left atrial pressure or left ventricular diastolic pressure ≤15 mm Hg, and a concomitant increased pulmonary vascular resistance, that is, >3 Wood units·m 2 . In addition to meeting the hemodynamic definition (requires catheterization of the right side of the heart) above, all potential causes of secondary PH, including PH resulting from pulmonary venous hypertension (PH group II), for example, disease of the left side of the heart, PH caused by chronic lung disorders such as cystic fibrosis (PH group III), PH resulting from chronic thromboembolic disease (PH group IV), and PH associated with miscellaneous conditions (PH group V), must be excluded before the diagnosis of PAH can be confirmed.…”

Section: Pulmonary Hypertension: Primary Prevention and Treatment Of mentioning

confidence: 99%

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

Giglia¹,

Massicotte²,

Tweddell³

et al. 2013

Circulation

298

245

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“…In a study by Frank et al, improved 5-year (63% vs 38%) and 10-year survival (39% vs 20%) were reported in warfarin-treated versus warfarinnaive patients with iPAH and drug-induced PAH. 16 A systematic review demonstrated a survival benefit of anticoagulation therapy in 488 iPAH patients, and included one case series, three retrospective cohort studies and one prospective cohort study. 17 In contrast, two retrospective cohort studies did not support these findings.…”

Section: Observational Studies Of Anticoagulation In Pahmentioning

confidence: 99%

“…Observational studies evaluating a role for anticoagulation in PAH, with mortality as an end point, are summarised in Table 1. 8,[13][14][15][16][18][19][20][21] While the findings of these observational studies are important for generating hypotheses regarding potential benefits of therapies, such studies may be biased because of non-random allocation of treatment and 'confounding by indication'.…”

Section: Observational Studies Of Anticoagulation In Pahmentioning

confidence: 99%

Should patients with systemic sclerosis‐related pulmonary arterial hypertension be anticoagulated?

Nikpour

Stevens

Proudman

et al. 2013

Internal Medicine Journal

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Pulmonary arterial hypertension (PAH) is a major cause of mortality in scleroderma and despite 'advanced' therapies confers a median survival of less than 5 years. Anticoagulation in systemic sclerosis-related PAH (SSc-PAH) is currently one of the most contentious issues in the management of patients with connective tissue disease. While some studies have shown a survival benefit with warfarin therapy in this disease, others have not. Accordingly, a state of clinical equipoise exists in relation to anticoagulation in SSc-PAH. With an over fivefold reduction in mortality demonstrated in some observational studies, the issue of anticoagulation in SSc-PAH demands resolution through a well-designed randomised controlled trial.

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The Effect of Anticoagulant Therapy in Primary and Anorectic Drug-Induced Pulmonary Hypertension

Cited by 227 publications

References 25 publications

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Surrogate End Points in Pulmonary Arterial Hypertension: Assessing the Response to Therapy

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

Should patients with systemic sclerosis‐related pulmonary arterial hypertension be anticoagulated?

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