The lowest relative doses were seen for the two beraprost trials (average: 7.7-fold lower) (see Table S1). 3.4. 95% CI: 1.5, 3.3). Compared to placebo, site pain associated with subcutaneously administered treprostinil was the most significant likely adverse event (OR = 17.5; 95% CI: 11.1, 27.1). Parenteral PMs were associated with fewer adverse effects overall. The overall efficacy of PMs to improve 6-minute Acarbose walk distance by 16.3 meters was significant (95% CI: 13.0, 19.7). Decreases in pulmonary vascular resistance index (SMD = ?5.5; 95% CI: ?10.1, ?0.9; 0.10. Statistic value 0.05 was regarded as statistically significant for the outcomes. RevMan software package (Review Manager, Version 5.2, The Cochrane Collaboration, Oxford, UK) and Stata 12.0 (College Station, TX, USA) were employed for statistical analyses. Subgroup analyses were performed comparing different drug types and different routes of administration. To investigate the effect of therapies given in the 30 days preceding trial initiation, the trials were split into three groups: those given non-PAH specific therapy including oxygen, digoxin, calcium channel blockers, anti-coagulants and diuretics, termed supportive therapy; those given non-prostanoid PAH-specific therapy including endothelin receptor antagonists (ERAs) and phosphodiesterase type 5 inhibitors (PDE-5i); those given prostacyclin therapy which in this case included only epoprostenol. Investigating the effect of background treatment designed dividing trials into two groups: those who were receiving other PAH-specific treatment at a stable monitored dose and those trials in which patients were not. In this case, concomitant therapies included ERA and PDE-5is usually only. The other groups were defined as not given any PAH-specific therapy on any specific dosing regimen but were treated with supportive therapies (as previously defined) when necessary. 3. Results 3.1. Study Characteristics Initial searching highlighted 1802 articles, of which 297 met the RCT filter and search criteria (See Physique S1). Abstract critiquing of the latter recognized 35 papers as highly relevant, out of which 14 papers were included in this study. All studies included were multi-centre trials, with a median trial length of 12 weeks (range: 8 to 156). Patients were given PMs via continuous subcutaneous (SC) infusion (treprostinil), continuous intravenous (IV) infusion (treprostinil), repeated daily inhalation (treprostinil, iloprost) or daily oral administration (beraprost, treprostinil, selexipag). Although the quality of assessment of the analysed papers was high, a potential discord of interest could not be excluded due to funding sources (See Figures S2 and S3). 3.2. Patient Characteristics Within the studies, a total of 3518 patients were included in the meta-analysis; 1846 treated with PMs and 1672 given placebo. Patients enrolled were mostly female (77%) and of a similar age (imply = 47 years, SD = 7) and were diagnosed with mostly Class II (25%) or class III (69%) PAH. The aetiology of PAH patients was mainly idiopathic PAH (68%), with over half of the remaining patients (19%) having connective tissue diseases (CTDs; including scleroderma). Within individual trials, patient cohorts were adjusted for age, gender, and disease severity between placebo and treatment groups. In all trials, patients were receiving non-specific therapy, including seven in which patients were also receiving PAH-specific treatment in the form of an ERA and/or a PDE-5i, described as combination therapy. Where available, the clinical trial statement was referred to, including associated unpublished information. A brief description of the trials basic characteristics is usually shown in Table 1. Table 1 Summary of clinical trials including prostacyclin mimetics compared against placebo. thead th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Study /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Drug /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Admin. Route /th th align=”center” valign=”middle” style=”border-top:solid Acarbose thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Study Length/Weeks /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Mean Daily Dose/mg # /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Therapy Type /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Pre-Trial Therapy /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Treatment Patients /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Control Patients /th th align=”center” valign=”middle”.Pulmonary vascular resistance index was significantly decreased by PM therapy (SMD = ?3.6; 95% CI: ?6.8, ?0.4; em I /em 2 = 99%). (OR = 2.2; 95% CI: 1.5, 3.3). Compared to placebo, site pain associated with subcutaneously administered treprostinil was the most significant likely adverse event (OR = 17.5; 95% CI: 11.1, 27.1). Parenteral PMs were associated with fewer adverse effects overall. The overall efficacy of PMs to improve 6-minute walk distance by 16.3 meters was significant (95% CI: 13.0, 19.7). Decreases in pulmonary vascular resistance index (SMD = ?5.5; 95% CI: ?10.1, ?0.9; 0.10. Statistic value 0.05 was regarded as statistically significant for the outcomes. RevMan software package (Review Manager, Version 5.2, The Cochrane Collaboration, Oxford, UK) and Stata 12.0 (College Station, TX, USA) were employed for statistical analyses. Subgroup analyses were performed comparing different drug types and different routes of administration. To investigate the effect of therapies given in the 30 days preceding trial initiation, the trials were split into three groups: those given non-PAH specific therapy including oxygen, digoxin, calcium channel blockers, anti-coagulants and diuretics, termed supportive therapy; those given non-prostanoid PAH-specific therapy including endothelin receptor antagonists (ERAs) and phosphodiesterase type 5 inhibitors (PDE-5i); those given prostacyclin therapy which in this case included only epoprostenol. Investigating the effect of background treatment meant dividing trials into two groups: those who were receiving other PAH-specific treatment at a stable monitored dose and those trials in which patients were not. In this case, concomitant therapies included ERA and PDE-5is only. The other groups were defined as not given any PAH-specific therapy on any specific dosing regimen but were treated with supportive therapies (as previously defined) when necessary. 3. Results 3.1. Study Characteristics Initial searching highlighted 1802 articles, of which 297 met the RCT filter and search criteria PCDH9 (See Figure S1). Abstract reviewing of the latter identified 35 papers as highly relevant, out of which 14 papers were included in this study. All studies included were multi-centre trials, with a median trial length of 12 weeks (range: 8 to 156). Patients were given PMs via continuous subcutaneous (SC) infusion (treprostinil), continuous intravenous Acarbose (IV) infusion (treprostinil), repeated daily inhalation (treprostinil, iloprost) or daily oral administration (beraprost, treprostinil, selexipag). Although the quality of assessment of the analysed papers was high, a potential conflict of interest could not be excluded due to funding sources (See Acarbose Figures S2 and S3). 3.2. Patient Characteristics Within the studies, a total of 3518 patients were included in the meta-analysis; 1846 treated with PMs and 1672 given placebo. Patients enrolled were mostly female (77%) and of a similar age (mean = 47 years, SD = 7) and were diagnosed with mostly Class II (25%) or class III (69%) PAH. The aetiology of PAH patients was mainly idiopathic PAH (68%), with over half of the remaining patients (19%) having connective tissue diseases (CTDs; including scleroderma). Within individual trials, patient cohorts were adjusted for age, gender, and disease severity between placebo and treatment groups. In all trials, patients were receiving non-specific therapy, including seven in which patients were also receiving PAH-specific treatment in the form of an ERA and/or a PDE-5i, described as combination therapy. Where available, the clinical trial report was referred to, including associated unpublished information. A brief description of the trials basic characteristics is shown in Table 1. Table 1 Summary of clinical trials involving prostacyclin mimetics compared against placebo. thead th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Study /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Drug /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Admin. Route /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Study Length/Weeks /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Mean Daily Dose/mg # /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Therapy Type /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Pre-Trial Therapy /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin”.Thirteen studies [31,33,34,36,37,38,39,40,41,42,43] recorded headache as a common side-effect associated with PM therapies (OR = 3.6; 95% CI: 2.4, 5.4; em I /em 2 = 82%). 3518 PAH patients, outcome and adverse event data were meta-analysed by drug type and route of administration. Prostacyclin mimetics comparison demonstrated a more significant discontinuation of the IP-selective agonist, selexipag, due to an adverse event (OR = 2.2; 95% CI: 1.5, 3.3). Compared to placebo, site pain associated with subcutaneously administered treprostinil was the most significant likely adverse event (OR = 17.5; 95% CI: 11.1, 27.1). Parenteral PMs were associated with fewer adverse effects overall. The overall efficacy of PMs to improve 6-minute walk distance by 16.3 meters was significant (95% CI: 13.0, 19.7). Decreases in pulmonary vascular resistance index (SMD = ?5.5; 95% CI: ?10.1, ?0.9; 0.10. Statistic value 0.05 was regarded as statistically significant for the outcomes. RevMan software package (Review Manager, Version 5.2, The Cochrane Collaboration, Oxford, UK) and Stata 12.0 (College Train station, TX, USA) were employed for statistical analyses. Subgroup analyses were performed comparing different drug types and different routes of administration. To investigate the effect of therapies given in the 30 days preceding trial initiation, the tests were split into three organizations: those given non-PAH specific therapy including oxygen, digoxin, calcium channel blockers, anti-coagulants and diuretics, termed supportive therapy; those given non-prostanoid PAH-specific therapy including endothelin receptor antagonists (ERAs) and phosphodiesterase type 5 inhibitors (PDE-5i); those given prostacyclin therapy which in this case included only epoprostenol. Investigating the effect of background treatment designed dividing tests into two organizations: those who were receiving additional PAH-specific treatment at a stable monitored dose and those tests in which individuals were not. In this case, concomitant treatments included ERA and PDE-5is definitely only. The additional organizations were defined as not given any PAH-specific therapy on any specific dosing routine but were treated with supportive therapies (as previously defined) when necessary. 3. Results 3.1. Study Characteristics Initial searching highlighted 1802 content articles, of which 297 met the RCT filter and search criteria (See Number S1). Abstract critiquing of the second option identified 35 papers as highly relevant, out of which 14 papers were included in this study. All studies included were multi-centre tests, having a median trial length of 12 weeks (range: 8 to 156). Individuals were given PMs via continuous subcutaneous (SC) infusion (treprostinil), continuous intravenous (IV) infusion (treprostinil), repeated daily inhalation (treprostinil, iloprost) or daily oral administration (beraprost, treprostinil, selexipag). Although the quality of assessment of the analysed papers was high, a potential discord of interest could not be excluded due to funding sources (See Numbers S2 and S3). 3.2. Patient Characteristics Within the studies, a total of 3518 individuals were included in the meta-analysis; 1846 treated with PMs and 1672 given placebo. Individuals enrolled were mostly female (77%) and of a similar age (imply = 47 years, SD = 7) and were diagnosed with mostly Class II (25%) or class III (69%) PAH. The aetiology of PAH individuals was primarily idiopathic PAH (68%), with over half of the remaining individuals (19%) having connective cells diseases (CTDs; including scleroderma). Within individual tests, patient cohorts were adjusted for age, gender, and disease severity between placebo and treatment organizations. In all tests, individuals were receiving non-specific therapy, including seven in which individuals were also receiving PAH-specific treatment in the form of an ERA and/or a PDE-5i, described as combination therapy. Where available, the medical trial statement was referred to, including connected unpublished information. A brief description of the tests basic characteristics is definitely shown in Table 1. Table 1 Summary of clinical tests including prostacyclin mimetics compared against placebo. thead th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Study /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Drug /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Admin. Route /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Study Size/Weeks /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Mean Daily Dose/mg # /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Therapy Type /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Pre-Trial Therapy /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Treatment Patients /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Control Patients /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ % br / NYHA Class III /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ % br / IPAH /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ % br / CTD /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ % br / Female /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Mean Age/year /th /thead Simonneau et al., 2002 [31]TreprostinilSC120.83 #Monotherapy30 days no prostanoids2332368158178144.5McLaughlin et al., 2003 [32]TreprostinilSC81.16 #MonotherapySupportive therapy *159-1000–Rubenfire et al., 2007 [33]TreprostinilSC82.87 #MonotherapyPatients must have been receiving epoprostenol therapy for 3 months1484171148645.5Hiremath et al., 2010 [34]TreprostinilIV124.77 #MonotherapySupportive therapy *3014959556132McLaughlin et al., 2010 [35]TreprostinilInhaled121.40Combination (Bosentan)Bosentan for 3 months1151209856358154Tapson et al., 2012 [36]TreprostinilOral16 Combination (ERA and/or PDE-5i)PDE-5i and or ERA for +3 months at a.