The quality of evidence is downgraded by study limitations (unclear allocation concealment).
A Cochrane review [Abstract] 1 included 9 RCTs of mixed duration (3 days-52 weeks) with a total of 1175 participants (NYHA functional classes II-IV).
Subgroup analyses reported by individual studies showed a better exercise capacity in participants with PPH, than those participants with PH secondary to other diseases. Side effects and adverse events were common in the studies.
Another Cochrane review [Abstract] 2 included 17 studies (median study duration 12 weeks) with a total of 3 765 mostly adult subjects pulmonary arterial hypertension (PAH). Fifteen studies compared a prostacyclin analogue (4 intravenous, 1 subcutaneous, 5 oral, and 5 inhaled) with placebo/conventional treatment, and 2 studies compared selexipag (an oral selective IP prostacyclin receptor agonist) to placebo.
Prostacyclin improved WHO functional class compared to control (table T1). Improvement occurred with intravenous (OR 14.96, 95% CI 4.76 to 47.04), and inhaled (OR 2.94, 95% CI 1.53 to 5.66), but not with oral preparations. There was a small, statistically significant improvement in six-minute walk distance, 6MWD (MD 19.50 metres, 95% CI 14.82 to 24.19; 13 studies, n=2 283), though it did not meet the minimum clinically important threshold of 41 metres. Clinically significant increase was obseved with intravenous (MD 91.76 metres, 95% CI 58.97 to 124.55), but not with non-intravenous preparations (subcutaneous 16.00 metres, oral 14.76 metres, inhaled 26.97 metres). Mortality was reduced in the intravenous (OR 0.29, 95% CI 0.12 to 0.69; 4 studies, n=255), but not in the non-intravenous studies (OR 0.82, 95% CI 0.48 to 1.40; 12 studies, n=2 299). Prostacyclins improved cardiopulmonary haemodynamics, dyspnoea, and quality of life compared to control. When only subcutaneous/inhaled studies were included the effect was still significant, but the magnitude was smaller, and there was no difference in oral studies.Adverse events (vasodilation, headache T1, jaw pain, diarrhoea, nausea/vomiting, myalgias, upper respiratory tract events, extremity pain, and infusion site reactions) increased in all prostacyclin preparations . There was a 12%-25% risk of serious non-fatal events (sepsis, haemorrhage, pneumothorax and pulmonary embolism) in the intravenous studies.
Outcome | Relative effect (95% CI) | Risk with control | Risk with prostacyclin (95% CI) | Participants (studies) |
---|---|---|---|---|
Improvement in WHO functional class | OR 2.39(1.72 to 3.32) | 116 per 1000 | 239 per 1000(185 to 304) | 1 066(8 studies) |
Mortality | OR 0.60(0.38 to 0.94) | 39 per 1000 | 24 per 1000(15 to 37) | 2 554(15 studies) |
Headache | OR 3.16 (2.62 to 3.80) | 277 per 1000 | 529 per 1000(95% CI 501 to 593) | 2 351(12 studies) |
Two studies (n=1 199) compared oral selexipag to placebo. There was a small improvement in 6MWD (12.62 metres, 95% CI 1.90 to 23.34), and no statistically significant effect for WHO functional class (OR 1.61, 95% CI 0.17 to 15.63). The effect of selexipag on the risk of death was uncertain (RD 0.02, 95% CI -0.00 to 0.04). There was less clinical worsening with selexipag (OR 0.47, 95% CI 0.37 to 0.60), but more side effects (vasodilation, headache, jaw pain, diarrhoea, nausea/vomiting, pain in the extremities, and myalgias).
Primary/Secondary Keywords