Background:

Systemic sclerosis is an autoimmune disease that could significantly affect internal organs, increasing the mortality associated with the disorder. Pulmonary hypertension is one of the conditions that increase the morbidity and mortality of the disease. The aim of the study was to develop a systematic literature review about the different pharmacological treatments for systemic sclerosis-associated pulmonary hypertension.

Materials and methods:

A systematic literature review was made on Cochrane, PubMed and EMBASE. Randomized controlled clinical trials, controlled clinical trials, cohort and case-control studies using any of the available treatments such as prostacyclin analogs, endothelin receptor antagonists, phosphodiesterase inhibitors or soluble guanylate cyclase stimulants were included. The methodological quality of the studies was assessed using Cochrane methodology for clinical trials, and the SIGN tool was applied for cohort and case-control studies.

Results:

Initially, 870 studies were found, and 20 studies were finally included in the systematic review after applying inclusion and exclusion criteria. Most studies included Bosentan in the treatment strategies (N = 13). Also, most studies took data from the most important clinical trials for pharmacological treatment of pulmonary hypertension of several etiologies. Some studies using Bosentan did not give information about data regarding some outcomes. Half of the selected studies were clinical trials, of which two were randomized. The quality of these studies was good. The other half were observational studies, with moderate quality of evidence. In general, it was found that approved medications improve the 6-minute walk distance, WHO functional class, NYHA functional classification, or Borg dyspnea score, depending on the given dose in several studies, and also compound outcomes that include hospitalizations, clinical worsening, death, etc. Regarding mortality, there were significant differences in survival rates when comparing approved medications vs. placebo, being combined therapies superior to monotherapy. Measurements of hemodynamic variables such as cardiac index, pulmonary resistances, and pulmonary pressures were improved. Also, NT-proBNP levels were reduced, with some exceptions.

Conclusions:

In most studies with good quality of evidence, it was found an improvement in clinical and non-clinical outcomes, favoring the use of approved medications for the treatment of systemic sclerosis-associated pulmonary hypertension.

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