Differences in health policies for drug availability in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension across Latin America.

Treatment for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in Latin America differs between countries, with regard to disease etiology, health insurance coverage, and drug availability. A group of experts from Latin America, met to share regional experiences and propose possible lines of collaboration. The available evidence, regional clinical practice data, and the global context of the proceedings of the 6th World Symposium on Pulmonary Hypertension, held in Nice, France, in February 2018, were analyzed. Here, we discuss some priority concepts identified that could guide transnational interaction and research strategies in Latin America: (1) despite being evidence-based, the 6th World Symposium on Pulmonary Hypertension proceedings may not be applicable in Latin American countries; (2) proactive identification and diagnosis of patients in Latin America is needed; (3) education of physicians and standardization of appropriate treatment for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is vital; (4) our clinical experience for the treatment strategy for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is based on drug availability in Argentina, Brazil, Colombia and México; (5) there are difficulties inherent to the consultation of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, and access to treatment; (6) the importance of data generation and research of Latin American-specific issues related to pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is highlighted.

Riociguat in the Treatment of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a severe clinical condition that significantly affects patients' quality of life and survival. Since the emergence of prostanoids 45 years ago, different drugs acting on vasoconstriction/vasodilation mechanisms have been developed for the treatment of PAH. Current evidence shows that better results occur when combined therapy is initiated up-front with periodic and systematized evaluations for escalation and switching. Among these strategies, riociguat has a relevant role, supported by the results of several clinical studies. This document issues recommendations by a panel of experts who analysed and discussed the indications and limitations for riociguat in PAH in different institutions of the Mexican health system.

[Pulmonary arterial hypertension and renal impairment in patients from the National Institute of Cardiology Dr. Ignacio Chávez, Mexico]. / Hipertensión arterial pulmonar y deterioro renal en pacientes del Instituto Nacional de Cardiología Ignacio Chávez, México.

Objective: The objective of the study was to describe the clinical characteristics and the evolution of the severity of pulmonary arterial hypertension (PAH) and the degree of renal failure. Material and methods: A retrospective observational study was carried out in which the physical and electronic medical records of 60 patients older than 18 years with a diagnosis of pulmonary arterial hypertension were analyzed. Results: In our study, 11.4% of the severe PAH group worsened renal function at six months, and 13.6% of the participants worsened it at one year. In contrast, in the group with moderate PAH, 18.8% worsened at six months, and 12.5% worsened at one year. Also, the GFR at one year was 54.15 mL/min/1.73 m2 in the moderate PAH group and in the severe PAH group was 73.55 mL/min/1.73 m2. Conclusion: The results of this research suggest that the deterioration of kidney function is related to the severity of pulmonary arterial hypertension.

Macitentan in the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is an uncommon but lethal and progressive disease in which prostacyclin, nitric oxide and endothelin-1 pathways are disturbed and contribute to the pathophysiology of this disease. Endothelin receptor antagonists are a class of drugs that have been approved as PAH therapy. Macitentan is a lipophilic, tissue specific, dual receptor antagonist with a higher potency than bosentan and a reduced risk of hepatic injury. Macitentan has shown a reduction in morbidity and mortality due to PAH at long-term follow-up and improvements in hemodynamics, exercise capacity and functional class at the short term. Its main adverse events are nasopharyngitis, bronchitis and an increased risk of anemia. We review the clinical data of macitentan and its use in PAH.

Angiotensin converting enzyme 2 and angiotensin (1-7) axis in pulmonary arterial hypertension.

BACKGROUND: In animal models of pulmonary arterial hypertension (PAH), angiotensin-converting enzyme (ACE)2 and angiotensin (Ang)-(1-7) have been shown to have vasodilatory, antiproliferative, antifibrotic and antihypertrophic properties. However, the status and role of the ACE2-Ang(1-7) axis in human PAH is incompletely understood. METHODS: We studied 85 patients with a diagnosis of PAH of distinct aetiologies. 55 healthy blood donors paired for age and sex served as controls. Blood samples were obtained from the pulmonary artery in patients with PAH during right heart catheterisation. Peripheral blood was obtained for both groups. Ang(1-7) and -II were measured using zone capillary electrophoresis. Aldosterone, Ang(1-9), AngA and ACE2 were measured using ELISA, and ACE2 activity was determined enzymatically. RESULTS: Of the 85 patients, 47 had idiopathic PAH, 25 had PAH associated with congenital heart disease and 13 had PAH associated with collagen vascular disease. Compared to controls, patients with PAH had a higher concentration of AngII (median 1.03, interquartile range 0.72-1.88 pmol·mL-1 versus 0.19, 0.10-0.37 pmol·mL-1; p<0.001) and of aldosterone (88.7, 58.7-132 ng·dL-1 versus 12.9, 9.55-19.9 ng·dL-1; p<0.001). Conversely, PAH patients had a lower concentration of Ang(1-7) than controls (0.69, 0.474-0.91 pmol·mL-1 versus 4.07, 2.82-6.73 pmol·mL-1; p<0.001), and a lower concentration of Ang(1-9) and AngA. Similarly, the ACE2 concentration was higher than in controls (8.7, 5.35-13.2 ng·mL-1 versus 4.53, 1.47-14.3 ng·mL-1; p=0.011), whereas the ACE2 activity was significantly reduced (1.88, 1.08-2.81 nmol·mL-1 versus 5.97, 3.1-17.8 nmol·mL-1; p<0.001). No significant differences were found among the three different aetiological forms of PAH. CONCLUSIONS: The AngII-ACE2-Ang(1-7) axis appears to be altered in human PAH and we propose that this imbalance, in favour of AngII, plays a role in the pathogenesis of the severe PAH. Further mechanistic studies are warranted.

Advances in medical therapy for pulmonary arterial hypertension.

PURPOSE OF REVIEW: The purpose of this review is to demonstrate advances in the medical treatment of pulmonary arterial hypertension (PAH). Reviewed will be the evidence that favors the use of risk assessment in the treatment of PAH. Optimization of combination therapy depending on the risk or worsening will be reviewed. Finally, recent advances in new treatment strategies will be mentioned. RECENT FINDINGS: The use of therapies in sequence or in combination for the treatment of PAH has been shown to decrease morbidity and mortality. Tailoring these treatment strategies to a risk of worsening has been shown to decrease mortality and time to clinical worsening because of PAH. In addition, there have been several advances in the development of other medications separate from the three known pathogenic pathways in PAH. SUMMARY: In the last 15 years, 12 specific therapies have been approved for PAH. These therapies target three separate pathogenic pathways [the endothelin (ET), nitric oxide (NO) and prostacyclin (PGI2)]. As a result, treatment guidelines have tailored the treatment of PAH with these medications either as single drug therapy or in combination. Recently, other treatment pathways have been explored as new strategies for the treatment of PAH.

Medical therapies for pulmonary arterial hypertension.

Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an increase in pulmonary vascular resistance due to severe remodeling of the small pulmonary arteries. In PAH, the endothelial cells fail to maintain their homeostatic balance, with the consequent impaired production of vasodilators and over-expression of vasoconstrictors and proliferators. Current treatment of PAH is based on the discovery of three main pathways of endothelial dysfunction (prostacyclin, nitric oxide and endothelin-1), and includes drugs such as prostacyclin analogs, phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs). Recently approved drugs that act through these classic pathways include riociguat (cyclic GMP stimulator) and macitentan (a tissue specific dual ERA). However, several new drugs and new pathways are under study. New targeted therapies include tyrosine kinase inhibitors, Rho kinase inhibitors and serotonin receptor blockers. There are now ten drugs approved for the treatment of PAH that, alone or in combination, have changed the natural history of this disease. The new drugs will allow us to further modified the patients' life expectancy and move towards a cure.