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The Patient with Non-Group 2 Pulmonary Hypertension
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Sophia Anastasia Mouratoglou, George Giannakoulas
Riociguat is a novel agent, which also targets the NO pathway but by enhancing cGMP production. The target dose is 2.5 mg three times daily, and titration is driven by blood pressure. The favorable effects of riociguat on exercise capacity, hemodynamics, WHO functional class, and time to clinical worsening vs placebo were demonstrated in a clinical trial, in which almost half of the patients were already on background advanced treatment for PAH.55 In the REPLACE trial, which examined the effect of switching to riociguat in patients with inadequate response to PDE-5 inhibitors, clinical improvement was achieved in 41% of the 111 patients in the riociguat group and 20% of the 113 patients in the PDE-5 inhibitor group (OR 2.78; 95% CI 1.53–5.06; P=0.0007).56 Riociguat is also the only agent approved for inoperable or recurrent chronic thromboembolic PH after pulmonary endarterectomy.57
Pulmonary hypertension: Hemodynamic assessment and response to vasodilators
Published in Debabrata Mukherjee, Eric R. Bates, Marco Roffi, Richard A. Lange, David J. Moliterno, Nadia M. Whitehead, Cardiovascular Catheterization and Intervention, 2017
Myung H. Park, Vallerie V. Mclaughlin
The Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1 (CHEST-1) study enrolled 261 patients with inoperable CTEPH or per- sistent or recurrent PH after pulmonary thromboendar- terectomy (PTE) to receive either riociguat (0.5 to 2.5 mg, three times daily) or placebo. The CHEST-1 trial met its primary endpoint of showing significant improvement in 6MWD in CTEPH patients treated with riociguat, the first therapy ever to demonstrate such improvement in this population. It also demonstrated improvement in relevant secondary endpoints, including improvement in PVR and WHO FC. The most common reported side effects include headache, gastritis/reflux, dizziness, and hypotension. Cases of hemoptysis have also been reported. Riociguat received dual indications in PH, namely for patients with WHO Group 1 PH to improve exercise capacity, FC, and help delay clinical worsening; and for WHO Group 4 patients with inoperable CTEPH or recurrent or persistent PH post-thromboendarterectomy. It must also be noted that all patients with surgically accessible lesions should undergo surgical evaluation and that riociguat cannot replace surgical treatment that can restore normal cardio- pulmonary status.
Respiratory Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Ian Pavord, Nayia Petousi, Nick Talbot
For most patients (groups 2, 3 and 5), management focuses on treatment of the underlying condition. For patients with PAH (group 1) or chronic thromboembolic pulmonary hypertension (CTEPH, group 4), directed therapy is available. In the UK, such patients are referred to one of a small number of regional specialist centres: General management: Patients with PAH and CTEPH should normally be anticoagulated to prevent pulmonary emboli, and may benefit from diuretics and digoxin to support right ventricular function. Long-term oxygen therapy is indicated if PaO2 is <8 kPa. Pregnancy is associated with high mortality, so birth control is important.Medical therapy: In those responding to vasodilators at right heart catheterization, calcium channel blockers may be used. Other medical therapies include endothelin receptor antagonists (e.g. bosentan), phosphodiesterase inhibitors (e.g. sildenafil), and prostacyclin analogues (e.g. iloprost) or soluble guanylate cyclase stimulators (e.g. riociguat). Riociguat is the only medical therapy currently licensed for CTEPH.Surgery: In CTEPH with proximal thrombus, pulmonary endarterectomy conducted in a specialized PH centre is the treatment of choice.
Vericiguat for the treatment of heart failure with reduced ejection fraction
Published in Expert Review of Cardiovascular Therapy, 2023
Ahmed K. Siddiqi, Stephen J. Greene, Marat Fudim, Robert J Mentz, Javed Butler, Muhammad Shahzeb Khan
Of note, nitrate-treated patients, as well as female and black patients, may have been underrepresented in the VICTORIA trial, and further research into these patient categories will be beneficial. Moreover, the use of SGLT2 inhibitors was not approved during the VICTORIA trial. Hence, it would be important to conduct further analysis of how SGLT2 inhibitors impact vericiguat’s effects. Riociguat is another sGC stimulator that is approved by the FDA for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) [56]. Several trials, including Riociguat for the Treatment of Pulmonary Arterial Hypertension (PATENT-1) [57], Switching to Riociguat in Pulmonary Arterial Hypertension Patients with Inadequate Response to Phosphodiesterase-5 Inhibitors (RESPITE) [58], and Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension (CHEST-1) [59] have demonstrated the beneficial effects of riociguat in patients with symptomatic PAH and CTEPH, respectively. Vericiguat may have an additional benefit in patients with HFrEF with pulmonary hypertension, given its similar structure and vasodilatory action to riociguat [60]; however, further investigation is needed.
Emerging drugs for the treatment of scleroderma: a review of recent phase 2 and 3 trials
Published in Expert Opinion on Emerging Drugs, 2020
David Roofeh, Alain Lescoat, Dinesh Khanna
The primary endpoint was not met (change from baseline in mRSS at 12 months); the riociguat arm had a decrease in mRSS (−2.09) compared with the placebo arm (−0.77) (difference −2.34 [95% confidence interval −4.99 to 0.30], p = 0.08). The secondary endpoint of measuring improvement with ACR CRISS was not significantly different between the two arms, although the design of the trial was to detect prevention of progression, not disease improvement. Assessment of lung function showed an FVC% predicted without significant difference in the two arms. Signals for efficacy were found in the proportion of patients with prevention of worsening: fewer patients in the riociguat arm (compared to placebo) had progression of mRSS as defined by a > 5 units and ≥25% increase from baseline: 11/59 (vs. 22/60), more regression defined by a decrease of >5 units and ≥25% from baseline: 27/59 (vs. 18/60). Less patients developed new DUs in the riociguat arm (compared to placebo): 5/60 (vs. 12/60); the number of DUs at 52 weeks was also less in the riociguat arm: 12 (vs. 72). Almost all (96.7%) of patients on riociguat had an adverse event, most commonly mild gastrointestinal symptoms (gastroesophageal reflux disease, diarrhea, nausea) or nervous system disorders (dizziness, headache). Serious adverse events were reported in nine patients (15%).
Treatment of pulmonary hypertension with riociguat: a review of current evidence and future perspectives
Published in Expert Opinion on Pharmacotherapy, 2020
Afroditi K. Boutou, Georgia Pitsiou
In conclusion, riociguat is a novel, oral, first-in-class agent that is approved for the treatment of PAH and for the treatment of inoperable CTEPH or persistent/recurrent PH after PEA. In patients with PAH, riociguat was found to be efficient both in treatment-naive subjects and in subjects that had previously received ERAs or non-intravenous prostanoids. Large clinical trials are needed to head-to-head compare the efficacy of PH-specific drug combinations in this patient population. Since the transition from PDE5i to riociguat in patients with inadequate PDE5i response seems to be beneficial, the most important clinical question remains how can we recognize PAH patients who could respond better to initial riociguat than PDEi therapy. The use of specific biomarkers would be very appealing, but no such have been yet identified. Future studies are needed in order to evaluate whether the approach of drug switch is beneficial in PAH and which specific baseline markers could guide the optimal treatment selection for each patient.