کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5954280 | 1173313 | 2014 | 12 صفحه PDF | دانلود رایگان |

BACKGROUNDDeficient nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling results from endothelial dysfunction and may underlie impaired cardiac relaxation in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and pulmonary hypertension (PH). The acute hemodynamic effects of riociguat, a novel soluble guanylate cyclase stimulator, were characterized in patients with PH and HFpEF.METHODSClinically stable patients receiving standard HF therapy with a left ventricular ejection fraction > 50%, mean pulmonary artery pressure (mPAP) ⥠25 mm Hg, and pulmonary arterial wedge pressure (PAWP) > 15 mm Hg at rest were randomized to single oral doses of placebo or riociguat (0.5, 1, or 2 mg). The primary efficacy variable was the peak decrease in mPAP from baseline up to 6 h. Secondary outcomes included hemodynamic and echocardiographic parameters, safety, and pharmacokinetics.RESULTSThere was no significant change in peak decrease in mPAP with riociguat 2 mg (n = 10) vs placebo (n = 11,P= .6). However, riociguat 2 mg significantly increased stroke volume (+9 mL [95% CI, 0.4-17];P= .04) and decreased systolic BP (â12 mm Hg [95% CI, â22 to â1];P= .03) and right ventricular end-diastolic area (â5.6 cm2[95% CI, â11 to â0.3];P= .04), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or pulmonary vascular resistance. Riociguat was well tolerated.CONCLUSIONSIn patients with HFpEF and PH, riociguat was well tolerated, had no significant effect on mPAP, and improved exploratory hemodynamic and echocardiographic parameters.TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01172756; URL:www.clinicaltrials.gov
Journal: Chest - Volume 146, Issue 5, November 2014, Pages 1274-1285