Practical management of riociguat in patients with pulmonary arterial hypertension

Abstract

Riociguat is one of several approved therapies available for patients with pulmonary arterial hypertension (PAH). Treatment should be initiated and monitored at an expert center by a physician experienced in treating PAH, and the dose adjusted in the absence of signs and symptoms of hypotension. In certain populations, including patients with hepatic or renal impairment, the elderly, and smokers, riociguat exposure may differ, and dose adjustments should therefore be made with caution according to the established scheme. Common adverse events are often easily managed, particularly if they are discussed before starting therapy. Combination therapy with riociguat and other PAH-targeted agents is feasible and generally well tolerated, although the coadministration of phosphodiesterase type 5 inhibitors (PDE5i) and riociguat is contraindicated. An open-label, randomized study is currently ongoing to assess whether patients who do not achieve treatment goals while receiving PDE5i may benefit from switching to riociguat. In this review, we provide a clinical view on the practical management of patients with PAH receiving riociguat, with a focus on the opinions and personal experience of the authors.The reviews of this paper are available via the supplemental material section.

“On Water” Palladium Catalyzed Direct Arylation of 1H-Indazole and 1H-7-Azaindazole

“…After succeeding in developing a “greener” pathway to synthesize C3-arylated 1 H -indazole, we extended the methodology to prepare C3-arylated pyrazolo[3,4- b ]pyridine, also known as azaindazole, which is an 1 H -indazole isostere and is often used as a key pharmacophore in drug design [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. Despite the enormous biological interest of C3-arylated pyrazolo [3,4- b ]pyridines, only one work has been reported by Lavard and Popowycz [ 38 ], addressing the functionalization of this motif via direct arylation.…”

“…Although this reported method is efficient, it is relatively energywasting, using heating at 160 °C for a long period of 3 days and organic solvent. For this reason, we decided to test our conditions developed to prepare C3-arylated pyrazolo[3,4-b]pyridine using the After succeeding in developing a "greener" pathway to synthesize C3-arylated 1H-indazole, we extended the methodology to prepare C3-arylated pyrazolo [3,4-b]pyridine, also known as azaindazole, which is an 1H-indazole isostere and is often used as a key pharmacophore in drug design [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57]. Despite the enormous biological interest of C3-arylated pyrazolo [3,4- one work has been reported by Lavard and Popowycz [38], addressing the functionalization of this motif via direct arylation.…”

Vericiguat: The Fifth Harmony of Heart Failure with Reduced Ejection Fraction

“…Activators of sGCs, such as cinaciguat, increase cGMP levels through direct (NO-independent) activation of sGCs, and are theoretically helpful in patients with acute heart failure or advanced heart failure (and therefore with a greater degree of reduction in NO levels related to oxidative stress and endothelial dysfunction); however, their clinical use is limited by symptomatic hypotension [ 20 , 21 ]. In contrast, sGC stimulators (riociguat and vericiguat), by increasing the sensitivity of sGC to endogenous NO, exert a more physiologic action, which, while causing clinical benefits to be absent in the advanced stages of the disease (see below), justifies the lower rate of symptomatic hypotension [ 22 , 23 ].…”

Soluble guanylate cyclase stimulator riociguat in the palette of modern specific therapy for precapillary pulmonary hypertension: from the pathophysiological basis to the results of current research

“…Начальную дозу риоцигуата 1 мг 3 раза необходимо увеличивать на 0,5 мг 3 раза каждые две недели при отсутствии побочных явлений, индивидуальной непереносимости и симптомов артериальной гипотензии. Титрацию дозы до максимальной (7,5 мг/сутки) рекомендовано проводить с осторожностью в соответствии с установленной схемой, учитывая то, что в некоторых когортах пациентов -при наличии печеночной или почечной недостаточности, у пожилых людей, у пациентов, злоупотребляющих курением -экспозиция риоцигуата в организме может повышаться [33,34].…”