Riociguat found safe, effective for PAH with coexisting conditions
Analysis of 686 PAH patients with up to 4 cardiometabolic disorders
Treatment with Adempas (riociguat) is generally safe and effective for people with pulmonary arterial hypertension (PAH) and coexisting cardiometabolic conditions, or those that affect the heart and metabolism, according to a pooled analysis of clinical trials.
“Efficacy and risk assessment results suggest that [Adempas] can be beneficial for patients with PAH irrespective of the presence of comorbidities [coexisting conditions],” researchers wrote.
The study, “Safety and efficacy of riociguat in patients with pulmonary arterial hypertension and cardiometabolic comorbidities: Data from interventional clinical trials,” was published in The Journal of Heart and Lung Transplantation.
PAH is a type of pulmonary hypertension characterized by the narrowing of the pulmonary arteries, the blood vessels that transport blood through the lungs. This narrowing restricts blood flow and leads to high blood pressure, or hypertension, in these arteries, and makes the heart work harder to pump blood.
Adempas works by relaxing arterial muscle walls to boost blood flow
Adempas is an approved treatment for PAH and chronic thromboembolic pulmonary hypertension that works by relaxing arterial muscle walls, causing the arteries to widen, or vasodilate, thereby increasing blood flow and reducing blood pressure. It is a stimulator of soluble guanylate cyclase, a protein involved in vasodilation.
In the study, an international team of researchers assessed the effect of Adempas on PAH patients with coexisting cardiometabolic diseases, namely obesity, hypertension, diabetes mellitus, and coronary artery disease, which is when the blood supply to the heart is reduced or interrupted. They analyzed pooled data from several clinical trials, including the Phase 3 PATENT-1 study (NCT00810693), in which participants received Adempa, or a placebo added to stable background therapy, and its long-term extension PATENT-2 (NCT00863681).
It also included patients from the Phase 2 trial PATENT-PLUS (NCT01179334) comparing Adempas to a placebo plus stable sildenafil (approved under the brand names Revatio and Liqrev), and from the Phase 4 REPLACE trial (NCT02891850), in which patients switched to Adempas or continued on a phosphodiesterase-5 (PDE-5) inhibitor, a type of vasodilator therapy that includes sildenafil and tadalafil (sold as Adcirca).
Overall, 686 patients were included: 440 treated with Adempas, 132 who received a placebo, and 114 on PDE-5 inhibitors. Most patients (55%) had no coexisting conditions, 39% had one or two, and 6% had three or four.
Patients with more coexisting conditions generally had more adverse events. Among those treated with Adempas, mild to moderate treatment-related effects were more frequent in patients with three to four comorbidities (66%) than in those with one or two (48%) or with none (53%).
In contrast, the incidence of drug-related serious events, and of treatment discontinuation or death due to adverse events was similar across the groups, regardless of the number of co-existing conditions. Likewise, safety results in the placebo groups were largely consistent with those for Adempas. Of note, results showed less treatment-related side effects with PDE-5 inhibitors in the groups with up to two coexisting conditions (comparisons could not be made for patients with three to four other diseases, due to the very few cases within the PDE-5 inhibitors group).
“In conclusion, [Adempas] had an acceptable tolerability profile in PAH patients with cardiometabolic comorbidities, with most [adverse events] being mild or moderate in severity,” the researchers wrote.
Adempas-treated patients show significant increase in walking distance
Treatment efficacy was assessed by the six-minute walk test, with Adempas-treated patients showing a significant increase in mean walking distance after about three months of treatment. Notably, the improvement was reduced as the number of coexisting conditions increased. A similar effect was seen for NT-proBNP levels, a marker of heart failure.
Taken together, compared with a placebo and to PDE5 inhibitors, Adempas increased walking distance and reduced NT-proBNP levels across the different groups of coexisting conditions. It also reduced disease severity, assessed with the World Health Organization functional class, and improved prognosis for patients with up to two coexisting disorders.
“This analysis provides important information on the impact of PAH treatment in patients with such comorbidities,” the researchers noted. “It also highlights the need for future studies to evaluate the efficacy and safety of PAH therapies in these patients.”
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