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Correspondence |

Therapy for Pulmonary Arterial HypertensionTherapy for Pulmonary Arterial Hypertension.: Approved Dosages Should Be Prescribed in Clinical Practice FREE TO VIEW

Marcelo Basso Gazzana, MD, PhD; Marli Maria Knorst, MD, PhD
Author and Funding Information

From the Serviço de Pneumologia (Drs Gazzana and Knorst), Hospital de Clínicas de Porto Alegre; the Serviço de Pneumologia e Cirurgia Torácica (Dr Gazzana), Hospital Moinhos de Vento; and the Programa de Pós-Graduação em Ciências Pneumológicas (Drs Gazzana and Knorst), Universidade Federal do Rio Grande do Sul.

CORRESPONDENCE TO: Marcelo Basso Gazzana, MD, PhD, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos St, Porto Alegre, Brazil 90035-903; e-mail: mbgazzana@gmail.com


Editor’s Note: Authors are invited to respond to Correspondence that cites their previously published work. Those responses appear after the related letter. In cases where there is no response, the author of the original article declined to respond or did not reply to our invitation.

CONFLICT OF INTEREST: None declared.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(4):e126. doi:10.1378/chest.15-1215
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To the Editor:

In the last 20 years, many trials have been carried out to evaluate the benefits and risks of pulmonary arterial hypertension (PAH)-targeted therapies. Several studies and meta-analyses have shown these drugs improve symptoms, exercise capacity, and hemodynamic variables and prevent clinical deterioration and death in patients with PAH.1,2 In an observational study by Tan et al3 in a recent issue of CHEST (April 2015), the patients received variable dosages of different PAH medications. The data were compared with published cohorts, showing similar results. The authors’ conclusion was that, despite using low dosages of PAH medications, such therapeutic schemes were safe and cost-effective, allowing health agencies to potentially save money. However, some of the dosages used by Tan et al,3 such as tadalafil 10 or 20 mg/d, were less effective than 40 mg/d as shown in the Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) randomized double-blind clinical trial.4 Other dosages, such as bosentan 31.25 mg bid or sildenafil 25 mg/d, have never undergone phase 3 trials. In these cases, we do not know if the therapy will cause benefit, cause harm, or have no effect and perhaps waste funds. Obviously, in real life some patients do not tolerate the recommended dosage, but we should attempt to reach it.

The observational study reported by Tan et al3 has many limitations. Susceptibility bias and confounding factors, such as disease severity and cointerventions, lead to a high risk of error and, therefore, weak evidence. Furthermore, the authors conclude that their low dosage therapy strategy is safe and cost-effective. However, to determine cost-effectiveness in relation to medical outcomes, studies should use a specific methodology based on data from randomized clinical trials.

We are concerned about the suggestion from Tan et al3 vis-à-vis the suitability of prescribing low-dose therapy for patients with PAH. In clinical practice, to ensure that our patients with PAH get the proven benefits, we should follow the guidelines regarding dosage for the medication.

References

Galiè N, Manes A, Negro L, Palazzini M, Bacchi-Reggiani ML, Branzi A. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J. 2009;30(4):394-403. [CrossRef] [PubMed]
 
Zheng Y, Yang T, Chen G, Hu E, Gu Q, Xiong C. Prostanoid therapy for pulmonary arterial hypertension: a meta-analysis of survival outcomes. Eur J Clin Pharmacol. 2014;70(1):13-21. [CrossRef] [PubMed]
 
Tan GMY, Tay EL, Tai B-C, Yip JWL. Idiopathic pulmonary arterial hypertension in Asians: a long-term study on clinical outcomes. Chest. 2015;147(4):e160-e163. [CrossRef] [PubMed]
 
Galiè N, Brundage BH, Ghofrani HA, et al; Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group. Tadalafil therapy for pulmonary arterial hypertension [published correction appears inCirculation. 2011;124(10):e279]. Circulation. 2009;119(22):2894-2903. [CrossRef] [PubMed]
 

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References

Galiè N, Manes A, Negro L, Palazzini M, Bacchi-Reggiani ML, Branzi A. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J. 2009;30(4):394-403. [CrossRef] [PubMed]
 
Zheng Y, Yang T, Chen G, Hu E, Gu Q, Xiong C. Prostanoid therapy for pulmonary arterial hypertension: a meta-analysis of survival outcomes. Eur J Clin Pharmacol. 2014;70(1):13-21. [CrossRef] [PubMed]
 
Tan GMY, Tay EL, Tai B-C, Yip JWL. Idiopathic pulmonary arterial hypertension in Asians: a long-term study on clinical outcomes. Chest. 2015;147(4):e160-e163. [CrossRef] [PubMed]
 
Galiè N, Brundage BH, Ghofrani HA, et al; Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group. Tadalafil therapy for pulmonary arterial hypertension [published correction appears inCirculation. 2011;124(10):e279]. Circulation. 2009;119(22):2894-2903. [CrossRef] [PubMed]
 
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