The quality of evidence is downgraded by imprecice results (few patients).
A Cochrane review [Abstract] included 5 studies with a total of 962 adults diagnosed with pulmonary hypertension. The aetiology of pulmonary hypertension varied and included pulmonary artery hypertension (PAH, 2 studies), chronic thromboembolic pulmonary hypertension (CTEPH, 1 study) and left-sided heart failure subjects (2 studies). All studies were of relatively short duration (< 16 weeks). Four studies compared a soluble guanylate cyclase (sGC) stimulator riociguat with placebo and 1 study randomised patients receiving a phosphodiesterase-V inhibitor (sildenafil) to placebo or riociguat.
Overall, riociguat increased six-minute walking distance (6MWD) (MD 30.13 metres, 95% CI 5.29 to 54.96 metres, statistical heterogeneity I2 =64%; 3 studies, n=659). In patients with PAH there was no effect noted (MD 11.91 metres, 95% CI −44.92 to 68.75, statistical heterogeneity I2 =77%; 2 studies, n=398), and in CTEPH riociguat improved 6MWD (MD 45 metres, 95% CI 23.87 to 66.13 metres; 1 study, n=261). Data for left heart disease-associated PH was not available for pooling. When participants receiving phosphodiesterase inhibitors (sildenafil) were excluded, riosiguat increased 6MWD by a MD of 36 metres in PAH. The second primary outcome, mortality, showed no change on pooled analysis against placebo (Peto OR 0.57, 95% CI 0.18 to 1.80; 5 studies, n=899).
Pooled secondary outcomes included no statistically significant difference in World Health Organization (WHO) functional class (OR 1.53, 95% CI 0.87 to 2.72; 4 studies, n=858), no effect on clinical worsening (OR 0.45, 95% CI 0.17 to 1.14, statistical heterogeneity I2 =54%; 3 studies, n=842), and a reduction in mean pulmonary artery pressure (MD −2.77 mmHg, 95% CI −4.96 to −0.58; 5 studies, n=744). Reduction in mean pulmonary artery pressure was seen in patients with PAH (MD -3.5 mmHg, 95% CI -5.54 to -1.46; 1 study, n=344) and CTEPH (MD -4.8 mmHg, 95% CI -6.71 to -2.89; 1 study, n=240) but not in left heart disease.
There was no significant difference in serious adverse events on pooled analysis (OR 1.12, 95% CI 0.66 to 1.90; 5 studies, n=818) or when analysed at PAH (OR 0.93, 95% CI 0.22 to 3.83, statistical heterogeneity I2 = 53%; 2 studies, n=398), left heart disease associated subgroups (OR 1.56, 95% CI 0.78 to 3.13; 2 studies, n=159) or CTEPH subgroups (OR 1.29, 95% CI 0.65 to 2.56; 1 study, n=261).
Soluble guanylate cyclase (sGC) stimulators should not be taken by people also receiving phosphodiestase-V inhibitors or nitrates due to the risks of hypotension. CTEPH results are applicable to inoperable or recurrent CTEPH only, and CTEPH should always be considered a surgically curable condition before reviewing medical therapy.
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