sildenafil-citrate and beraprost

Topics: Administration, Oral; Adult; Antihypertensive Agents; Bosentan; Carbolines; Endothelin Receptor Antagonists; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Phenylpropionates; Phosphodiesterase 5 Inhibitors; Piperazines; Pulmonary Artery; Purines; Pyridazines; Pyrimidines; Randomized Controlled Trials as Topic; Sildenafil Citrate; Sulfonamides; Sulfones; Tadalafil; Vascular Resistance; Vasodilator Agents

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Bosentan; Drug Therapy, Combination; Epoprostenol; Humans; Hypertension, Pulmonary; Mice; Molecular Targeted Therapy; Piperazines; Protein Kinase Inhibitors; Purines; Rats; rho-Associated Kinases; Signal Transduction; Sildenafil Citrate; Sulfonamides; Sulfones; Vascular Resistance

Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of Controlled Trials, Korea med and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. The outcomes were the exercise capacity and adverse events. Four randomized controlled trials involving 109 subjects were included in the analysis. Two trials involved bosentan, one sildenafil and one beraprost. The studies varied in duration of treatment from 3 to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8). COPD with overt PH significantly improved the exercise capacity (mean difference, 111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference, 26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a significant effect in improving exercise capacity in COPD with overt PH.

Topics: Antihypertensive Agents; Bosentan; Clinical Trials as Topic; Databases, Factual; Epoprostenol; Humans; Hypertension, Pulmonary; Hypoxia; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Risk Factors; Sildenafil Citrate; Sulfonamides; Sulfones; Surveys and Questionnaires

This review assesses the available evidence supporting the use of drug combinations for the management of the various forms of pulmonary arterial hypertension (PAH). Ongoing and forthcoming randomized trials evaluating this strategy are also highlighted. Furthermore, new types of agents to treat PAH in the future are explored.

Topics: Adrenomedullin; Angiopoietin-1; Antihypertensive Agents; Benzamides; Bosentan; Drug Therapy, Combination; Eicosanoids; Epoprostenol; Genetic Therapy; Humans; Hypertension, Pulmonary; Imatinib Mesylate; Intracellular Signaling Peptides and Proteins; Piperazines; Platelet Aggregation Inhibitors; Prostaglandins; Protein Serine-Threonine Kinases; Purines; Pyrimidines; rho-Associated Kinases; Serotonin; Serotonin Plasma Membrane Transport Proteins; Sildenafil Citrate; Sulfonamides; Sulfones; Vasoactive Intestinal Peptide; Vasodilator Agents

Distal-type chronic thromboembolic pulmonary hypertension (CTEPH) is a fatal disease for which a new therapeutic strategy needs to be developed. We examined the effects of percutaneous transluminal pulmonary angioplasty (PTPA).. We prospectively enrolled 12 patients with distal-type CTEPH. After stabilizing their condition with pulmonary vasodilators, we then performed PTPA, which markedly improved pulmonary hemodynamics and pulmonary artery structure, as confirmed by angiography and optical coherence tomography, and also significantly improved their long-term prognosis compared with 39 historical controls.. PTPA is a promising therapeutic option for distal-type CTEPH.

Topics: Aged; Angioplasty; Antihypertensive Agents; Bosentan; Chronic Disease; Combined Modality Therapy; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Piperazines; Prognosis; Prospective Studies; Pulmonary Circulation; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Vasodilator Agents

Sildenafil and beraprost, as orally available pulmonary vasodilators, are used increasingly to treat pulmonary hypertension (PH). An evaluation was made, in patients with PH undergoing valvular heart surgery, as to whether preoperative combined oral sildenafil and beraprost treatment could induce synergistic and prolonged pulmonary vasodilation, or result in a loss of pulmonary selectivity.. Fifty patients scheduled for valvular heart surgery with a mean pulmonary arterial pressure (PAP) > 30 mmHg were randomly assigned to receive either 50 mg oral sildenafil + 40 microg beraprost, or a placebo, 15 min before the induction of anesthesia. Hemodynamic variables were measured intraoperatively.. The treatment group had a significantly lower systemic vascular resistance index at 60 min after medication. No other significant intergroup differences in hemodynamic variables were observed. In addition, significantly more patients in the treatment group required vasopressor therapy. In both groups, the PAP was significantly reduced by general anesthesia, and almost normalized after valvular heart surgery.. Preoperative oral sildenafil and beraprost treatment resulted in a loss of pulmonary selectivity, and did not provide any additional pulmonary vasodilation or favorable perioperative hemodynamics in patients with PH undergoing valvular heart surgery.

Topics: Adult; Aged; Anesthesia, General; Blood Pressure; Comorbidity; Drug Therapy, Combination; Epoprostenol; Female; Heart Valve Diseases; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Piperazines; Preoperative Care; Purines; Sildenafil Citrate; Sulfones; Vascular Resistance; Vasoconstrictor Agents; Vasodilator Agents

BACKGROUND To explore the efficacy of beraprost sodium combined with sildenafil and its effects on the vascular endothelial function and inflammation in left heart failure patients complicated with pulmonary arterial hypertension. MATERIAL AND METHODS A total of 80 patients with left heart failure complicated with pulmonary arterial hypertension was enrolled as the subjects of this study and assigned into an observation group (n=40) and a control group (n=40) using a random number table. The changes in pulmonary arterial hypertension-associated indicators at 3 months after treatment and the alterations in the levels of cardiac function-associated biochemical indicator brain natriuretic peptide (BNP), inflammatory factor tumor necrosis factor alpha (TNF-alpha), and mean pulmonary arterial pressure during treatment were compared between the 2 groups. RESULTS At 3 months after treatment, the pulmonary arterial hypertension-associated indicators human urotensin II and calcitonin gene-related peptide in the observation group were lower and higher, respectively, than those in control group. Moreover, the observation group had significantly lower BNP and TNF-alpha levels and mean pulmonary arterial pressure than the control group. After intervention, the echocardiographic parameters left ventricular ejection fraction (LVEF), cardiac output (CO), and stroke volume (SV) in both groups were significantly higher than those before intervention, and the observation group had significantly higher LVEF, SV, and CO than the control group after intervention. CONCLUSIONS Beraprost sodium combined with sildenafil for left heart failure complicated with pulmonary arterial hypertension can effectively improve pulmonary arterial hypertension, alleviate left heart failure, and reduce inflammatory responses, thereby achieving better clinical efficacy in patients.

Topics: Aged; Aged, 80 and over; Echocardiography; Endothelial Cells; Epoprostenol; Exercise Tolerance; Female; Heart Failure; Humans; Inflammation; Male; Middle Aged; Pulmonary Arterial Hypertension; Pulmonary Artery; Sildenafil Citrate; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Ventricular Function, Right

Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.

Topics: Aged; Aged, 80 and over; Antibodies, Antinuclear; Autoantibodies; Bosentan; Cardiac Catheterization; Centrioles; Drug Therapy, Combination; Endothelin Receptor Antagonists; Epoprostenol; Female; Forced Expiratory Volume; Humans; Imatinib Mesylate; Protein Kinase Inhibitors; Pulmonary Arterial Hypertension; Pulmonary Diffusing Capacity; Pyrimidines; Scleroderma, Systemic; Sildenafil Citrate; Sulfonamides; Tadalafil; Tomography, X-Ray Computed; Vasodilator Agents

This study aims to assess the cost-effectiveness and budget impact of adopting sildenafil to the benefits package for the indication of pulmonary arterial hypertension (PAH), compared to beraprost.. Based on a societal perspective, a model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs).. The economic model calculated the incremental cost-effectiveness ratio (ICER) per QALY gained for using sildenafil as first-line therapy compared to beraprost for the patient in functional class (FC) II and III, i.e. USD 3098 and USD 2827, respectively. The results indicated that in spite of sildenafil being more expensive than beraprost, generic sildenafil could potentially be a good value for money since ICER per QALY is below one times gross domestic product (GDP) per capita in Indonesia. Furthermore, budget impact analysis estimated that the incremental budget needed within 5 years for including sildenafil compared to beraprost for PAH patients starting in FC II and FC III was USD 436,775 and USD 3.6 million, respectively.. Compared to beraprost, sildenafil would be preferable for the treatment of PAH patients in FC II and FC III in Indonesia. The additional budget for adopting sildenafil compared to beraprost as the treatment of PAH in the benefits package was estimated at around USD 4.0 million.

Topics: Budgets; Cost-Benefit Analysis; Epoprostenol; Humans; Hypertension, Pulmonary; Indonesia; Sildenafil Citrate; Vasodilator Agents

This study aims to compare the lifetime costs and health outcomes of both first-line and sequential combination treatments with standard treatment for pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) (PAH-CHD) patients.. A cost-utility analysis was performed using a Markov model based on a societal perspective. One-way and probabilistic sensitivity analyses were performed to investigate the effect of parameter uncertainty.. As first-line treatments, both beraprost (incremental cost-effectiveness ratio (ICER) = 192,752 and 201,308 Thai baht (THB) per quality-adjusted life year (QALY) gained) and sildenafil (ICER = 249,770 and 226,802 THB per QALY gained) seemed cost-effective for PAH-CHD patients aged ≤30 years in functional classes II and III, respectively, while no treatment was cost-effective for the sequential combination therapy.. Sildenafil should be included in the National Drug List of Essential Medicines as the first-line treatment for PAH-CHD, and its price per dose should be negotiated to be reduced by 43-57%.

Topics: Adult; Budgets; Cost-Benefit Analysis; Drug Costs; Drugs, Essential; Epoprostenol; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Markov Chains; Quality-Adjusted Life Years; Sildenafil Citrate; Thailand; Vasodilator Agents

Recent vasodilating drugs have improved prognosis of Pulmonary arterial hypertension (PAH). Some reports describe the merits of combination therapies for PAH, and this study evaluated the efficacy and safety of phosphodiesterase type 5 inhibitors (PDE5i) combination therapy, using sildenafil and tadalafil, for multi-drug-resistant PAH.. We retrospectively analyzed 7 consecutive refractory patients with PAH administered either sildenafil 60 mg or tadalafil 40 mg as well as both ERA and prostanoid as combination therapies. All were started on the dual PDE5i (sildenafil and tadalafil at maximum dose).. Treatment was generally well tolerated without severe adverse events. On completion of the study, the seven patients received right heart catheterization and the 6-minute walk test (6WMT) 9.6 ± 1.4 months after initiation of the dual PDE5i therapy, showing significant improvements in hemodynamic parameters and exercise tolerance. Mean pulmonary arterial pressure and pulmonary vascular resistance decreased from 47.9 ± 9.7 to 41.7 ± 9.2 mmHg (P = 0.004) and 9.3 ± 2.7 to 6.7 ± 2.9 mmHg (P = 0.018), respectively. Cardiac index and 6MWT also increased from 2.8 ± 0.9 to 3.1 ± 0.8 L/min/m(2) (P = 0.026) and 353 ± 60 to 382 ± 62 m (P = 0.014), respectively.. The findings support dual PDE5i therapy as a new treatment option for refractory PAH.

Topics: Adult; Antihypertensive Agents; Bosentan; Cardiac Catheterization; Drug Therapy, Combination; Endothelin Receptor Antagonists; Epoprostenol; Exercise Test; Female; Humans; Hypertension, Pulmonary; Middle Aged; Phenylpropionates; Phosphodiesterase 5 Inhibitors; Pilot Projects; Prostaglandins; Pulmonary Wedge Pressure; Pyridazines; Retrospective Studies; Sildenafil Citrate; Sulfonamides; Tadalafil; Treatment Outcome; Vascular Resistance; Young Adult

Right ventricular (RV) dysfunction, caused by severe pulmonary hypertension (PH), is associated with high mortality because of RV failure. However, some patients can suffer from sudden cardiac death (SCD). We hypothesized that severe PH can cause RV arrhythmogenesis, leading to SCD. We sought to investigate arrhythmogenesis in PH. Optical mapping analysis (OMP) with an electrophysiological study (EPS) and pathological examination were performed in a monocrotaline (MCT)-induced rat PH model. Rats were injected with MCT (60 mg/kg), and OMP was performed in isolated Langendorff-perfused hearts. OMP revealed abnormal RV conduction delays and abnormal patterns, along with elevated RV pressure. In addition, impaired action potential duration dispersion (APDd), an index of myocardial repolarization instability, was observed only in the RVs with severe PH. The EPS demonstrated that lethal arrhythmias were induced by burst pacing to the RV when deteriorated APDd became evident. This arrhythmogenesis was inhibited by combination treatment with sildenafil and beraprost (SIL + BERA). RT-PCR showed an mRNA up-regulation of Type I collagen and down-regulation of connexin-43 in the RV at 5 weeks after MCT injection. Pathological examination revealed pulmonary vascular remodeling and RV hypertrophy with interstitial fibrosis, which was substantially reduced by SIL + BERA. Immunohistochemistry also revealed connexin-43 degradation in the RVs with severe PH. In contrast, connexin-43 was well preserved, and no lethal arrhythmias were induced by burst pacing to the RV in the absence of PH after SIL + BERA. In conclusion, RV electrical remodeling, including impaired APDd, causes arrhythmogenesis in severe PH, potentially associated with SCD attributable to PH.

Topics: Animals; Arrhythmias, Cardiac; Cardiotonic Agents; Collagen Type I; Connexin 43; Death, Sudden, Cardiac; Drug Therapy, Combination; Epoprostenol; Gene Expression Regulation; Heart; Humans; Hypertension, Pulmonary; Male; Monocrotaline; Organ Culture Techniques; Piperazines; Purines; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Sulfones; Ventricular Dysfunction, Right; Ventricular Remodeling; Voltage-Sensitive Dye Imaging

To elucidate left ventricular function in pulmonary hypertension, we measured parameters of left ventricular as well as right ventricular function by echocardiography in 11 patients with pulmonary hypertension (idiopathic pulmonary artery hypertension in 4, chronic thromboembolic pulmonary hypertension in 5, and other pulmonary hypertension in 2). The percent change in these parameters 6 months after treatment with pulmonary artery vasodilators (beraprost in 8 and sildenafil in 3) was assessed. There was a correlation between the relative change in right ventricular systolic pressure (RVSP) and the relative changes in left ventricular outflow tract velocity-time integral (r = -0.730, P = 0.011) and mitral valve velocity-time integral (r = -0.621, P = 0.041). However, there was no correlation between the relative change in RVSP and the relative changes in left ventricular ejection fraction, left ventricular diastolic dimension, and systolic blood pressure. The relative change in RVSP was also correlated with the relative change in early diastolic myocardial velocity at the medial mitral annulus (r = -0.675, P = 0.023). Reduction of RVSP by pulmonary artery vasodilators might increase left ventricular preload, leading to an increase in stroke volume. Right ventricular load reduction might improve left ventricular diastolic function in patients with pulmonary hypertension, possibly through altered interventricular septal performance.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Diastole; Echocardiography, Doppler; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Linear Models; Male; Middle Aged; Mitral Valve; Piperazines; Purines; Sildenafil Citrate; Stroke Volume; Sulfones; Systole; Time Factors; Treatment Outcome; Vasodilator Agents; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right; Ventricular Pressure

Pulmonary hypertension (PH) is an infrequently reported complication after hematopoietic stem cell transplantation, and its etiology and therapeutic strategies, especially in infants, remain unclear. We report a case of severe PH that developed in an infant with acute leukemia following administration of busulfan as a preconditioner for cord blood transplantation; the case was successfully treated with sildenafil and beraprost, which to our knowledge is the first reported successful use of this regimen in PH following transplantation for infantile leukemia. From a review of all previous reports, use of busulfan in infants may raise the risk of developing PH, and unlike definitive pulmonary veno-occlusive disease, PH in this subgroup may be reversible by early detection and treatment.

Topics: Cord Blood Stem Cell Transplantation; Echocardiography; Epoprostenol; Humans; Hypertension, Pulmonary; Infant; Leukemia; Male; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tomography, X-Ray Computed; Treatment Outcome; Vasodilator Agents

The case is described herein of a patient with alveolar capillary dysplasia with double-outlet right ventricle and duodenal atresia who survived for a remarkably long time. The newborn girl was born at a gestational age of 36 weeks and weighed 1926 g. One min after delivery the Apgar score was 4. The patient had persistent pulmonary hypertension (PH) and needed nitric oxide inhalation and i.v. epoprostenol all through her life. Although other oral medications for PH were tried, they could not be used in practice because of gastrointestinal complications. The patient died on the 237 th day of life as a result of worsening PH associated with infection.

Topics: Administration, Inhalation; Bosentan; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epoprostenol; Fatal Outcome; Female; Follow-Up Studies; Humans; Infant, Newborn; Nitric Oxide; Persistent Fetal Circulation Syndrome; Piperazines; Platelet Aggregation Inhibitors; Pulmonary Alveoli; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Time Factors; Vasodilator Agents

Selective right pulmonary arteriography and 3-dimensional computed tomography revealed multiple severe stenoses of the peripheral pulmonary artery associated with poststenotic aneurysms in a 65-year-old woman. She was referred to the hospital for evaluation of dry cough, gradually increasing dyspnea and multiple nodular shadows on a chest radiograph. Echocardiography and cardiac catheterization showed severe pulmonary hypertension, though other structural heart diseases or well-characterized congenital syndromes were ruled out. She was diagnosed as isolated peripheral pulmonary artery branch stenosis. Recent advances in CT technology enable a less-invasive assessment of pulmonary artery, and can be useful in the management of pulmonary arterial hypertension.

Topics: Aged; Aneurysm; Arterial Occlusive Diseases; Cardiac Catheterization; Constriction, Pathologic; Cough; Dyspnea; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Imaging, Three-Dimensional; Oxygen Inhalation Therapy; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfones; Tomography, X-Ray Computed; Ultrasonography; Vasodilator Agents; Warfarin

Pulmonary arterial hypertension (PAH) is a rare complication of glycogen storage disease (GSD), and several cases with a poor outcome have been reported. A 17-year-old boy, who was diagnosed with GSD at 1 year of age, complained of shortness of breath on exertion, and was diagnosed with PAH based on the echocardiographic findings. Beraprost sodium (BPS) was started, and his symptoms improved after 3 months of treatment. Eighteen months later, he experienced frequent episodes of syncope. Because increasing the dose of BPS was ineffective, he was admitted to hospital. The echocardiogram showed marked elevation of the right ventricular pressure and low cardiac output, and his symptoms deteriorated despite continuous infusion of olprinone hydrochloride. Because a single dose of sildenafil increased his cardiac output, treatment with 25 mg sildenafil twice daily was started. His symptoms gradually ameliorated, and 3 weeks later he left the hospital. Two months after starting sildenafil, the cardiac index and the serous B-type natriuretic peptide concentration had become normal. Sildenafil may be effective in patients with secondary PAH and in patients who have developed tolerance to BPS.

Topics: Administration, Oral; Adolescent; Antihypertensive Agents; Drug Tolerance; Echocardiography; Electrocardiography; Epoprostenol; Glycogen Storage Disease Type I; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Syncope; Treatment Outcome; Vasodilator Agents

We report a 16-year-old man with severe heart failure due to idiopathic pulmonary arterial hypertension (IPAH). The patient was initially treated with a combination of beraprost, a prostacyclin analog, and sarpogrelate, a serotonin receptor inhibitor. However, he was unresponsive to the treatment. We then changed the treatment to sildenafil, and his condition dramatically improved. Sildenafil has an immediate pulmonary vasodilator effect in patients already receiving vasodilators for IPAH.

Topics: Adolescent; Drug Therapy, Combination; Epoprostenol; Humans; Hypertension, Pulmonary; Male; Piperazines; Purines; Serotonin Antagonists; Sildenafil Citrate; Succinates; Sulfones; Treatment Outcome; Vasodilator Agents

Pulmonary arterial hypertension (PAH) is commonly associated with CREST (Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly, and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of PAH. However, little is known about the long-term hemodynamic effects of sildenafil, and the potential role of sildenafil in long-term combination with beraprost, an oral prostacyclin analogue, remains unclear. We therefore examined the hemodynamic effect of oral sildenafil alone and when coadministered with beraprost in a patient with PAH associated with CREST syndrome. Traces of the acute hemodynamic effects of beraprost (20 microg) disappeared after 2 hours. In contrast, the acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours. After 1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost (20 microg) 3 times daily, the fall in pulmonary artery pressure and pulmonary vascular resistance was sustained (31% in both). Furthermore, the patient had significantly improved her 3-minute walk test and NYHA function class without significant adverse effects at the reported doses. The findings indicate that oral sildenafil is a potent pulmonary vasodilator that appears to act synergistically with oral beraprost to cause sustained pulmonary vasodilatation in a patient with PAH associated with CREST syndrome.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; CREST Syndrome; Cryoprotective Agents; Drug Therapy, Combination; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Wedge Pressure; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

A 70-year-old man with a past history of lung resection for early stage lung cancer was admitted to our hospital because of worsening exertional dyspnea. Right heart catheterization revealed severe pulmonary arterial hypertension (PAH) with pulmonary vascular resistance of 1671.64 dyne.sec.cm(-5). The patient was treated with sildenafil added to an oral prostacyclin analog, beraprost, and long term oxygen therapy. His exertional dyspnea continued to improve until his sudden death following nasal bleeding. Autopsy revealed marked thickening of pulmonary arteriolar walls, but no recurrence of lung cancer, significant pulmonary embolism or pulmonary parenchymal disease. His PAH could not be explained by the mild airway obstruction or sleep apnea syndrome, and unrelated pulmonary vascular disease was suspected.

Topics: Aged; Epoprostenol; Humans; Hypertension, Pulmonary; Lung Neoplasms; Male; Oxygen Inhalation Therapy; Phosphodiesterase Inhibitors; Piperazines; Pneumonectomy; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfones; Vascular Resistance

Although sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of pulmonary hypertension (PH), safety and effectiveness have not been studied during coadministration with beraprost, an oral prostacyclin analogue. To address this issue, we administered oral beraprost (40 microg) on day 1 and beraprost (40 microg) plus sildenafil (25 mg) on days 2 to 6 patients with moderate to severe PH. Although sildenafil plus beraprost produced transient flushing in 2 of 6 patients, systemic hemodynamics and arterial and venous gas analyses were similar in comparisons between the 2 treatment groups. In contrast, sildenafil plus beraprost therapy resulted in a 2.2-fold greater reduction in mean pulmonary arterial pressure and a 1.6-fold greater reduction in pulmonary vascular resistance compared with beraprost alone, and reductions in these parameters persisted longer with combination therapy than with beraprost alone. Addition of oral sildenafil to beraprost appears to represent a safe and effective therapeutic option, at least in the acute phase, for patients with pulmonary hypertension.

Topics: Administration, Oral; Aged; Drug Therapy, Combination; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones

Sildenafil, an oral phosphodiesterase type-5 inhibitor, has vasodilatory effects through a cyclic guanosine 3', 5'-monophosphate-dependent mechanism, whereas beraprost, an oral prostacyclin analog, induces vasorelaxation through a cAMP-dependent mechanism. We investigated whether the combination of oral sildenafil and beraprost is superior to each drug alone in the treatment of pulmonary hypertension. Rats were randomized to receive repeated administration of saline, sildenafil, beraprost, or both of these drugs twice a day for 3 weeks. Three weeks after monocrotaline (MCT) injection, there was significant development of pulmonary hypertension. The increases in right ventricular systolic pressure and ratio of right ventricular weight to body weight were significantly attenuated in the Sildenafil and Beraprost groups. Combination therapy with sildenafil and beraprost had additive effects on increases in plasma cAMP and cyclic guanosine 3', 5'-monophosphate levels, resulting in further improvement in pulmonary hemodynamics compared with treatment with each drug alone. Unlike MCT rats given saline, sildenafil, or beraprost alone, all rats treated with both drugs remained alive during 6-week follow-up. These results suggest that combination therapy with oral sildenafil and beraprost attenuates the development of MCT-induced pulmonary hypertension compared with treatment with each drug alone.

Topics: Administration, Oral; Analysis of Variance; Animals; Cyclic GMP; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epoprostenol; Hemodynamics; Hypertension, Pulmonary; Male; Piperazines; Probability; Purines; Random Allocation; Rats; Rats, Wistar; Sildenafil Citrate; Sulfones; Survival Rate; Vascular Patency; Vasodilator Agents

Topics: Animals; Disease Models, Animal; Drug Therapy, Combination; Epoprostenol; Hypertension, Pulmonary; Male; Piperazines; Purines; Random Allocation; Rats; Rats, Wistar; Reference Values; Sensitivity and Specificity; Sildenafil Citrate; Sulfones; Treatment Outcome

Topics: Epoprostenol; Humans; Hypertension, Pulmonary; Nitric Oxide; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents