Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension (original) (raw)

New Insights in the Treatment Strategy for Pulmonary Arterial Hypertension

Cardiovascular Drugs and Therapy, 2006

Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.

Therapeutic Strategies in Pulmonary Arterial Hypertension

European Cardiology Review, 2012

Pulmonary arterial hypertension (PAH) is a serious and life-threatening condition for which the prognosis remains poor. Treatment options include endothelial receptor antagonists, phosphodiesterase (PDE5) inhibitors and prostanoids. Despite all demonstrating good short-term efficacy, none of the currently available drug therapies are curative. Treatment with prostanoids is complex and requires careful monitoring and management through a specialist centre. Furthermore, clinical efficacy is dependent on adequate up-titration of the drug. Treatment should be individualised and modified according to clinical response, with the addition of other therapies if required. The importance of monitoring and modifying therapeutic regimes is discussed. There appears to be reluctance among patients and physicians to employ prostanoid therapy, though an aggressive first-line therapy may be appropriate in advanced cases.

Management Of Pulmonary Arterial Hypertension: A Brief Overview

2017

PAH is a progressive disease characterized by increased pulmonary vascular resistance, leading to chronic elevation in pulmonary arterial pressure resulting from restricted flow through the pulmonary arterial circulation. Various genetic mutations involving BMPR2, activin-like kinase type-1 receptor are associated with it. Treatment of PAH includes conventional treatments, and disease-specific treatments along with lifestyle modifications. Goals of treatment include alleviation of symptoms, with improvements in quality of life and survival. Several approved agents include prostacyclin and prostacyclin analogues, phosphodiesterase-5 inhibitors, soluble guanylyl cyclase stimulator, endothelin receptor antagonists. Currently, three drug classes have been US FDA-approved for chronic treatment of PAH: prostacyclin analogs, endothelin receptor antagonists (ERAs) and phosphodiesterase type 5 (PDE5) inhibitors. Due to a lack of convenient, effective treatments available for PH, new treatmen...

Key Articles and Guidelines in the Management of Pulmonary Arterial Hypertension: 2011 Update

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2012

ERA endothelin-receptor antagonist FPAH familial pulmonary arterial hypertension HAART highly active antiretroviral therapy IPAH idiopathic pulmonary arterial hypertension MPAP mean pulmonary artery pressure MRAP mean right atrial pressure NYHA New York Heart Association PCWP pulmonary capillary wedge pressure PDE-5 phosphodiesterase-type-5 PVR pulmonary vascular resistance SSRI selective serotonin receptor inhibitor ULN upper limit of normal SVO 2 peak or maximal oxygen consumption WHO World Health Organization OUTLINE Pathophysiology, Epidemiology, and Classification of PAH Management of Co-morbid Conditions and Risk Factors for PAH Pharmacologic Therapy for PAH Non-pharmacologic Therapy for PAH Investigational Therapy for PAH Pathophysiology, Epidemiology, and Classification of PAH Galiè N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of

Practical Considerations for the Pharmacotherapy of Pulmonary Arterial Hypertension

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2012

Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.

Medical treatment update on pulmonary arterial hypertension

Therapeutic advances in chronic disease, 2015

Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed.

Therapeutic advances in pulmonary arterial hypertension

Therapeutic advances in respiratory disease, 2008

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries inducing increased pulmonary arterial resistance. Conventional treatment is based on life style modification and nonspecific treatment (warfarine, diuretics, oxygen). Calcium channel blockers are vasodilatators that have been shown to be of great efficacy in a very specific subpopulation of patients with PAH. For the majority of patients, specific PAH therapies are still lacking. Numerous studies evaluating prostacyclin agonists, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors are now available to guide therapeutic choices. Despite those important advances there is still no cure for PAH. Fortunately, research is ongoing and many drugs show promises.

Clinical Trials Using Vasodilators in Pulmonary Arterial Hypertension:Where Do We Go from Here?

Reviews on Recent Clinical Trials, 2011

Background: The impact of treatment with vasodilators on the survival of patients with pulmonary arterial hypertension (PAH) remains uncertain. Despite several clinical trials have been carried out in the last 15 years, their primary objective was not to assess mortality but the changes on surrogate end points. Methods and results: We reviewed the results of all clinical trials with vasodilators in PAH and the main results of different metaanalysis. Clinical trials and systematic reviews confirm that vasodilator therapies in patients with PAH who are non-vasoreactive produce a consistent, statistically significant but a marginal effect on exercise capacity assessed by the six-minute walk test. The weighted mean difference (95% CI) achieved with epoprostenol (EPO) or other prostacyclin analogues (PCA), endothelin receptor antagonists (ETRA) and phosphodiesterase-type-5 inhibitors (PDE5-I) was 35.4 m (17.3-53.5), 46.1 m (38.1-54.2) and 33.8 m (24.8-42.7), respectively. When considering the cumulative effects within each drug family, no class of drug produced a statistically significant reduction in all cause mortality. The relative risk rates (95% CI) conferred by EPO or PCA, ETRA and PDE5-I were 0.66 (0.36-1.21), 0.48 (0.19-1.23) and 0.65 (0.16-2.67), respectively. Interpretation: Further trials utilizing similar classes of drugs, and following similar trial designs are unlikely to yield different results or offer any more clinical benefits. Given that PAH is a fatal disease this raises concerns about whether they are ethical to conduct or not. Future trials will need to utilize clinical endpoints rather than the ones that are easy to administer and will need to include longer durations of study and other strategies to test the durability of effect.