BACKGROUND: Few controlled clinical trials exist to support oral combination therapy in pulmonary arterial hypertension (PAH). METHODS: Patients with PAH (idiopathic [IPAH] or associated with connective tissue disease [APAH-CTD]) taking bosentan (62.5 or 125 mg twice daily at a stable dose for ≥3 months) were randomized (1:1) to sildenafil (20 mg, 3 times daily; n = 50) or placebo (n = 53). The primary endpoint was change from baseline in 6-min walk distance (6MWD) at week 12, assessed using analysis of covariance. Patients could continue in a 52-week extension study. An analysis of covariance main-effects model was used, which included categorical terms for treatment, baseline 6MWD (<325 m; ≥325 m), and baseline aetiology; sensitivity analyses were subsequently performed. RESULTS: In sildenafil versus placebo arms, week-12 6MWD increases were similar (least squares mean difference [sildenafil-placebo], -2.4 m [90% CI: -21.8 to 17.1 m]; P = 0.6); mean ± SD changes from baseline were 26.4 ± 45.7 versus 11.8 ± 57.4 m, respectively, in IPAH (65% of population) and -18.3 ± 82.0 versus 17.5 ± 59.1 m in APAH-CTD (35% of population). One-year survival was 96%; patients maintained modest 6MWD improvements. Changes in WHO functional class and Borg dyspnoea score and incidence of clinical worsening did not differ. Headache, diarrhoea, and flushing were more common with sildenafil. CONCLUSIONS: Sildenafil, in addition to stable (≥3 months) bosentan therapy, had no benefit over placebo for 12-week change from baseline in 6MWD. The influence of PAH aetiology warrants future study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00323297 (registration date: May 5, 2006).

• Klíčová slova
• Combination therapy, Sildenafil - Bosentan - pulmonary hypertension - randomized controlled trial -exercise test,
• MeSH
• antagonisté endotelinového receptoru aplikace a dávkování   škodlivé účinky   MeSH
• antihypertenziva aplikace a dávkování   škodlivé účinky   MeSH
• arteria pulmonalis účinky léků   patofyziologie   MeSH
• arteriální tlak účinky léků   MeSH
• bosentan MeSH
• časové faktory MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• inhibitory fosfodiesterasy 5 aplikace a dávkování   škodlivé účinky   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metoda nejmenších čtverců MeSH
• obnova funkce MeSH
• plicní hypertenze diagnóza   farmakoterapie   patofyziologie   MeSH
• senioři MeSH
• sildenafil citrát aplikace a dávkování   škodlivé účinky   MeSH
• sulfonamidy aplikace a dávkování   škodlivé účinky   MeSH
• test chůzí MeSH
• tolerance zátěže účinky léků   MeSH
• vazodilatancia aplikace a dávkování   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté endotelinového receptoru MeSH
• antihypertenziva MeSH
• bosentan MeSH
• inhibitory fosfodiesterasy 5 MeSH
• sildenafil citrát MeSH
• sulfonamidy MeSH
• vazodilatancia MeSH

The differentiation between chronic pulmonary thromboembolic hypertension (CTEPH) and pulmonary arterial hypertension (PAH) remains a clinical challenge. The aim of our study was to evaluate the usefulness of both echocardiographically and invasively derived pulmonary artery pulsatility indexes in the etiologic differentiation of patients with CTEPH and PAH. We retrospectively analyzed the results of echocardiographic and invasive hemodynamic examinations in 125 patients with either CTEPH (n = 62) or PAH (n = 63). Invasive data were obtained in 52 patients with CTEPH and 43 PAH patients. Using echocardiography, pulmonary artery systolic (PASP), diastolic (PADP) and mean (PAMP) pressures were estimated from velocities of tricuspid regurgitation and pulmonary regurgitation, respectively. Pulse pressure (PP) was calculated as the difference between PASP and PADP. To obtain pulmonary artery pulsatility indexes, we normalized PP by PASP (PP/PASP), by PAMP (PP/PAMP) and by PADP (PP/PADP). Pulsatility indexes assessed by echocardiography did not differ between CTEPH and PAH patients except for PP/PAMP [PP/PAMP (1.82 ± 0.33 vs. 1.40 ± 0.3, p < 0.001)]. Invasively derived pulsatility indexes were significantly higher in subjects with CTEPH (0.60 ± 0.08 vs. 0.53 ± 0.09 for PP/PASP; 0.98 ± 0.21 vs. 0.81 ± 0.21 for PP/PAMP; 1.58 ± 0.52 vs. 1.21 ± 0.41 for PP/PADP; all p < 0.001). The areas under the receiver-operating characteristic curves analysis showed that no cutoff value allowed discriminating between CTEPH and PAH by using echocardiographically or invasively derived pulsatility indices. Invasively derived pulmonary artery pulsatility indexes as well as echocardiographically determined PP/PAMP indexes are higher in CTEPH compared to PAH. However, due to the important overlap no optimal threshold values of these parameters can be given to allow satisfactory discrimination of the two diseases in clinical practice.

• MeSH
• arteria pulmonalis diagnostické zobrazování   patofyziologie   MeSH
• chronická nemoc MeSH
• diferenciální diagnóza MeSH
• dopplerovská echokardiografie * MeSH
• dospělí MeSH
• familiární plicní arteriální hypertenze MeSH
• krevní tlak MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• plicní embolie diagnóza   diagnostické zobrazování   patofyziologie   MeSH
• plicní hypertenze diagnóza   diagnostické zobrazování   patofyziologie   MeSH
• plicní oběh * MeSH
• prediktivní hodnota testů MeSH
• pulzatilní průtok * MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• senioři MeSH
• srdeční katetrizace * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH