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Background: Niacin induces the release of vasodilating prostaglandins, for which receptors are present within the pulmonary arterial circulation. We hypothesized that immediate-release niacin would reduce right ventricular systolic pressure in patients with pulmonary hypertension in a randomized, double-blinded, single-dose provocation study.Methods: We recruited inpatient subjects with a Doppler echocardiogram showing a peak tricuspid regurgitation (TR) jet velocity of 2.7 m/s or greater, and who were free of known pulmonary vascular disease. Subjects were randomized in a 1:2:2 ratio to receive a single dose of either placebo, niacin 100 mg or niacin 500 mg, respectively. TR jet velocities were measured immediately before, and 1 hour post dose, corresponding to peak niacin absorption and prostaglandin release. The primary endpoint was the change in mean TR jet velocity measured over ten successive cardiac cycles.Results: The baseline mean estimated right ventricular systolic pressure (RVSP) for all 49 subjects (25 male) was 51.9 ± 12.1 mm Hg. The primary endpoint of mean change in TR jet velocity was 0.016 ± 0.065 m/s in the placebo group, compared to -0.017 ± 0.065 m/s with niacin 100 mg, and -0.063 ± 0.038 m/s with niacin 500 mg (P = 0.63). The change in maximum estimated RVSP across the three drug groups was 0.2 ± 1.6 mm Hg, -1.3 ± 1.8 mm Hg and -2.2 ± 1.2 mm Hg (P = 0.62). In exploratory pairwise analysis in the high-dose niacin group (500 mg), the reduction in mean RVSP was from 50.9 ± 9.4 mm Hg to 48.7 ± 10.0 mm Hg (P = 0.09).Conclusions: A single dose of immediate-release niacin (100 mg or 500 mg) had no significant effect on RVSP 1 hour post administration. A nonsignificant dose-dependent trend for a modest reduction in RVSP, most notable in the 500 mg group, was noted. (ISRCTN number 12353191, registered April 23, 2015). [ABSTRACT FROM AUTHOR]