warfarin and Familial-Primary-Pulmonary-Hypertension

Idiopathic pulmonary arterial hypertension is a rare and progressive condition which is aggravated by the physiologic changes during pregnancy. Because of high mortality rate, most physicians recommend early termination of pregnancy in patients with idiopathic pulmonary arterial hypertension.. Here we describe a case of a 30-year-old primigravida Caucasian housewife with functional class 1 idiopathic pulmonary arterial hypertension and a positive vasoreactive response to adenosine who had a full-term non-complicated delivery. Right-sided heart catheterization before the pregnancy showed severe pulmonary hypertension with mean pulmonary arterial pressure of 60 mmHg, and pulmonary vascular resistance of 12.2 WU. Vasoreactivity was positive after infusion of 200 μg/kg per minute adenosine. During pregnancy, she did not receive medication other than prophylactic enoxaparin. She had an elective cesarean section under general anesthesia at 39 weeks of gestation without complication and delivered a healthy baby. After delivery, her hemodynamic status was stable. One month postpartum, she was in a stable clinical condition in functional class 1.. In pregnant patients with pulmonary arterial hypertension, decreased mortality has been observed over recent years particularly in patients with well-controlled pulmonary pressure and a positive vasoreactivity test.

Topics: Adult; Anticoagulants; Cesarean Section; Echocardiography; Enoxaparin; Familial Primary Pulmonary Hypertension; Female; Heparin; Humans; Infant, Newborn; Live Birth; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Warfarin

Anticoagulation is a common treatment modality in patients with pulmonary arterial hypertension (PAH). Further studies are needed to appropriately assess the risk/benefit ratio of anticoagulation, particularly in PAH patients receiving PAH-specific therapies.. We use observational long-term data on PAH patients treated with subcutaneous (SQ) treprostinil from a large open-label study. Patients were followed for up to 4 years. The use of warfarin and bleeding events were recorded.. At total of 860 patients (age [mean±SD] 46±15 years, 76% female, 83% Caucasian, 49% idiopathic PAH, and 76% New York Heart Association [NYHA] functional class III) were included. All patients received SQ treprostinil (15% also other pulmonary hypertension [PH]-therapies) and 590 (69%) received warfarin during the study. The proportions of women, African American, and idiopathic pulmonary hypertension (IPAH) patients were higher in the group receiving warfarin. A higher proportion of patients with congenital heart disease and portopulmonary hypertension did not receive warfarin. There were no differences in unadjusted long-term survival between PAH patients receiving warfarin or not (log-rank test, P value=.69), even when only considering idiopathic PAH (P=.32). In addition, no difference was found in adjusted long-term survival both in PAH (P=.84) and idiopathic PAH patients (P=.44) based on the use of warfarin. Furthermore, no survival difference based on the use of warfarin were noted between propensity score-matched PAH patients (P=.37).. Long-term anticoagulation with warfarin was not associated with any significant effect on survival in PAH or idiopathic PAH patients treated with SQ treprostinil.

Topics: Adult; Anticoagulants; Antihypertensive Agents; Chi-Square Distribution; Epoprostenol; Familial Primary Pulmonary Hypertension; Female; Hemorrhage; Humans; Infusions, Subcutaneous; Kaplan-Meier Estimate; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Warfarin

Topics: Disease Management; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Registries; Survival Rate; Warfarin

Topics: Disease Management; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Registries; Survival Rate; Warfarin

Idiopathic pulmonary arterial hypertension (IPAH) is an incurable disease with high mortality. Although most studies recommend anticoagulation treatment for IPAH, the benefits are uncertain, particularly in Korea, where it has not been studied. The purpose of this study was to evaluate survival outcomes of Korean patients with IPAH treated with warfarin.. We performed a retrospective cohort study of patients diagnosed previously with pulmonary arterial hypertension (PAH) at the Asan Medical Center in Korea, between January 1994 and February 2013. We excluded patients with associated PAH, patients who did not undergo right heart catheterization (RHC), and patients with a positive vasoreactivity test. Patients in the study cohort were classified into a "warfarin group" and a "non-warfarin group," according to the treatment they received during the first year after diagnosis.. We identified 31 patients with IPAH and a negative vasoreactivity test on RHC. Median patient age was 36.0 years, and 23 patients (74.2%) were female. The median time from the onset of symptoms to diagnosis was 19.0 months, and the most common presenting symptom was dyspnea. Survival rates of the patients at 1, 3, 5, and 10 years were 90.2%, 79.5%, 62.7%, and 34.8%, respectively. The mean survival period was 12.0 years in the warfarin group and 6.1 years in the non-warfarin group. Warfarin treatment had significant survival benefits in patients with IPAH (p = 0.023).. Warfarin treatment substantially improved survival outcomes in Korean cases of IPAH.

Topics: Adult; Anticoagulants; Asian People; Familial Primary Pulmonary Hypertension; Female; Humans; Kaplan-Meier Estimate; Male; Proportional Hazards Models; Protective Factors; Republic of Korea; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Warfarin

Warfarin is recommended in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and idiopathic PAH (IPAH) to improve survival. There is no evidence to support this in SSc-PAH and the evidence in IPAH is conflicting. We evaluated the ability of warfarin to improve survival using 2 large SSc-PAH and IPAH cohorts.. The effect of warfarin on all-cause mortality was evaluated. Bayesian propensity scores (PS) were used to adjust for baseline differences between patients exposed and not exposed to warfarin, and to assemble a matched cohort. Bayesian Cox proportional hazards models were constructed using informative priors based on international PAH expert elicitation.. Review of 1138 charts identified 275 patients with SSc-PAH (n = 78; 28% treated with warfarin) and 155 patients with IPAH (n = 91; 59% treated with warfarin). Baseline differences in PAH severity and medications were resolved using PS matching. In the matched cohort of 98 patients with SSc-PAH (49 treated with warfarin), the posterior median hazard ratio (HR) was 1.06 [95% credible interval (CrI) 0.70, 1.63]. In the matched cohort of 66 patients with IPAH (33 treated with warfarin), the posterior median HR was 1.07 (95% CrI 0.57, 1.98). The probability that warfarin improves median survival by 6 months or more is 23.5% in SSc-PAH and 27.7% in IPAH. Conversely, there is a > 70% probability that warfarin provides no significant benefit or is harmful.. There is a low probability that warfarin improves survival in SSc-PAH and IPAH. Given the availability of other PAH therapies with demonstrable benefits, there is little reason to use warfarin to improve survival for these patients.

Topics: Anticoagulants; Bayes Theorem; Cause of Death; Cohort Studies; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Proportional Hazards Models; Scleroderma, Systemic; Treatment Outcome; Warfarin

Warfarin use in scleroderma (SSc)-associated pulmonary arterial hypertension (PAH) and idiopathic PAH (IPAH) is controversial. A prerequisite for a trial is the demonstration of community uncertainty. We evaluated experts' beliefs about the effect of warfarin on 3-year survival in SSc-PAH and IPAH, and factors that influence warfarin use.. PAH experts attending the 2008 American College of Rheumatology or American Thoracic Society meetings expressed the probability of 3-year survival without and with warfarin and their degree of uncertainty by applying adhesive dots, each representing a 5% weight of probability, in "bins" on a line, creating a prior probability distribution or prior. Using a numeric rating scale, participants rated factors that influence their use of warfarin.. Forty-five experts (44% pulmonologists, 38% rheumatologists, 16% cardiologists, 2% internists) underwent the belief elicitation interview. In SSc-PAH, the mean probabilities of 3-year survival without and with warfarin were 54% and 56%, respectively. Pessimistic experts believe that warfarin worsens survival by 7%. Optimistic experts believe that warfarin improves survival by 13%. In IPAH, the mean probabilities of 3-year survival without and with warfarin were 68% and 76%. Factors (mean rating out of 10, 0 = not at all important, 10 = extremely important) that influence experts' use of warfarin were functional class (5.4), age (5.4), pulmonary artery pressure (5.2), peripheral vascular disease (3.6), disease duration (2.8), and sex (1.7).. Bayesian priors effectively quantify and illustrate experts' beliefs about the effect of warfarin on survival in SSc-PAH and IPAH. This study demonstrates the presence of uncertainty about the effect of warfarin, and provides justification for a clinical trial.

Topics: Anticoagulants; Bayes Theorem; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Male; Practice Patterns, Physicians'; Scleroderma, Systemic; Surveys and Questionnaires; Survival Rate; Warfarin

Anticoagulation with warfarin is recommended for the treatment of patients with pulmonary arterial hypertension (PAH). However, the therapeutic benefit of anticoagulation has not yet been demonstrated experimentally or clinically. Here, rivaroxaban, an oral, direct factor Xa (FXa) inhibitor, was compared with warfarin and enoxaparin in the prevention of right ventricular (RV) dysfunction and hypertrophy in the monocrotaline (MCT) model of pulmonary hypertension.. Sprague-Dawley rats (n = 10 per group) were randomized to receive rivaroxaban, warfarin, enoxaparin, or placebo before receiving a subcutaneous injection of MCT 60 mg/kg or saline. Rivaroxaban and enoxaparin were administered for 28 days starting 4 h before MCT injection; warfarin was given for 35 days initiated 7 days before MCT injection. RV haemodynamics and hypertrophy were assessed 28 days after MCT administration. Rivaroxaban dose-dependently reduced systolic and end-diastolic RV pressure increase and RV hypertrophy. Warfarin reduced RV pressure increase only. Enoxaparin had no effect on either parameter. Severe bleeding occurred in four and five rats treated with warfarin and enoxaparin, respectively, whereas no overt bleeding was observed in rats treated with rivaroxaban.. Selective, direct inhibition of FXa by rivaroxaban effectively prevented RV dysfunction and hypertrophy in MCT-injected rats, indicating a role for coagulation factors in experimental pulmonary hypertension. Clinical investigation of the impact of early and continued administration of a specific FXa inhibitor such as rivaroxaban on the course of PAH should be considered.

Topics: Animals; Blood Coagulation; Enoxaparin; Factor Xa; Factor Xa Inhibitors; Familial Primary Pulmonary Hypertension; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Morpholines; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rivaroxaban; Thiophenes; Thrombosis; Warfarin