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Medscape
a day ago
- Health
- Medscape
Speeding Up Vericiguat Target Dose in HFrEF Shown Safe
Ditching the standard two-step pathway to the target 10-mg dose of vericiguat in patients with heart failure with reduced ejection fraction (HFrEF) and instead employing a one-step protocol can be done safely and overcome the clinical inertia many of these patients encounter, the lead investigator of a prospective clinical trial of the one-step approach said. The 2022 American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines recommend starting patients with HFrEF on a 2.5-mg dose of vericiguat, a soluble guanylate cyclase activator, then stepping up to a 5-mg dose enroute to reaching a target of 10 mg. VELOCITY Study Results Stephen Greene, MD However, the VELOCITY study found nine of 10 patients safely tolerated starting on the 5-mg dose and skipping the recommended 2.5-mg step, Stephen Greene, MD, an advanced heart failure specialist at Duke Cardiology Clinic in Durham, North Carolina, reported at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2025. The study was simultaneously published in the European Journal of Heart Failure . 'We know from real-world evidence studies that, in US practice, there are many patients who are initiated on 5-mg vericiguat already, but now we have, actually, clinical data to suggest that this 5-mg initiation dose does appear to be safe among our patients that haven't had recent hypotension,' Greene told Medscape Medical News. The VELOCITY results make the case for updating the clinical guidelines for vericiguat, he added. The rationale for the study was to determine if starting patients closer to the target dose would give them a better chance of getting to and staying on the 10-mg target dose, according to Greene. 'Simplifying this process is one of the best ways to improve implementation for all our guideline-directed medical therapies,' Greene said. VELOCITY was a single-arm, two-week-long prospective trial that enrolled 106 patients with heart failure with an ejection fraction < 45% who were well-treated with background guideline-directed medical therapies. The primary endpoint was tolerability of 5-mg vericiguat dose after 2 weeks. Overall, 93.4% of patients tolerated the dose, including 90.6% in the group with worsening heart failure and 96.2% whose condition remained stable. Fourteen patients (13.2%) had an adverse event associated with treatment. One, a case of facial angioedema, was severe but the rest were considered mild. Four patients (3.8%) discontinued treatment because of an adverse event. VELOCITY also compared outcomes of those starting on the 5-mg dose with outcomes in the VICTORIA trial, which started patients on the 2.5-mg dose. In VICTORIA, 97.2% of patients tolerated the 2.5-mg starting dose over 2 weeks. Among patients with worsening heart failure, again 97.2% of VICTORIA patients tolerated the 2.5-mg treatment well, compared with 90.6% taking the 5-mg starting dose in VELOCITY. Greene also noted that patients in VELOCITY had 'the exact same mean reduction' in systolic blood pressure as those in VICTORIA: Both up to 3.2 mm HG on average. In VICTORIA, the placebo group also experienced a reduction in systolic blood pressure, he said, and the difference between the treatment and placebo groups was 1-to-2 mm HG. Had VELOCITY been a placebo study, the 3.2 mm HG reduction observed with the 5 mg dose 'likely would've been even further attenuated,' Greene said. 'This goes with what we already know about vericiguat, in that it seems to have minimal to no effect on systolic blood pressure.' Starting patients with HFrEF on 5 mg of vericiguat can help overcome 'clinical inertia' and increase the likelihood they will get to the 10-mg target dose, Greene said. 'Many of our patients with HFrEF never achieve target doses of guideline-directed medical therapies, and despite clinic visit after clinic visit, medication changes are, unfortunately, relatively rare,' Greene said. 'We see minimal medication titration, even when our patients have robust blood pressure, even when they have normal kidney function, even when we're talking about our inexpensive generic medications, we don't see many medication changes.' Time for Change, or 'Unique Strategy'? Ankeet S. Bhatt, MD, MBA, ScM Calling for a rewrite of clinical guidelines for using vericiguat in patients with HFrEF based on the VELOCITY results might be premature, Ankeet S. Bhatt, MD, MBA, ScM, a cardiologist and intensivist at Kaiser Permanente San Francisco Medical Center, told Medscape Medical News. 'VELOCITY really tests a unique strategy, reducing one of the steps in the titration of vericiguat, which may, if the clinical efficacy is confirmed in dedicated trials, bolster the confidence around early implementation at a higher dose of this therapy, without the need for an intra-dose titration,' Bhatt said. Validating the VELOCITY findings in a clinical trial 'might improve both acceptance from clinicians and the clinical implications about implementation of the therapy,' he added. Pairing the randomized clinical trial evidence with larger-scale real-world evidence would provide stronger evidence, he said. 'It's possible that there might be late effects or add-on effects that might either promote tolerability or might have safety concerns that we couldn't see in the context of this trial,' Bhatt said. 'So this is an important area that sets the stage, and when it's confirmed in real-world evidence, then I think we can make a compelling case that this might be an important addition to the guidance we already have.' This study was funded by Bayer and Merck Sharp & Dohme. Greene reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Corcept, Corteria Pharmaceuticals, CSL Vifor, Cytokinetics, Idorsia, Lexicon, Lilly, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche Diagnostics, Sanofi, scPharmaceuticals, Sumitomo, and Tricog Health. Bhatt reported consulting for Merck.
Medscape
2 days ago
- Health
- Medscape
Study Shows Safety of Pharma-Grade CBD for Myocarditis
An oral formulation of pharmaceutically manufactured cannabidiol (CBD) that targets inflammatory pathways in myocarditis and pericarditis has been shown to be as safe as placebo in not elevating cardiovascular risks, results of a prospective trial have shown. The placebo-controlled trial enrolled 89 people with a history of cardiovascular disease (CVD) and/or at least one major risk factor for the condition who had been hospitalized for noncritical COVID-19. Leslie Cooper Jr, MD 'There are 45 or so who received pharmacologically produced CBD who had no increase in overall or cardiovascular adverse events, and in particular there was no prolongation of the QT interval,' Leslie Cooper Jr, MD, chair of cardiovascular medicine at Mayo Clinic Florida in Jacksonville, Florida, told Medscape Medical News . Cooper presented a poster on the study at Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2025. The findings confirmed the safety of CBD doses up to 7.5 mg/kg twice daily used in the ARCHER trial in myocarditis and the MAVERIC trial in pericarditis, Cooper said. Study Shows Safety Signal The researchers designed the study during the COVID-19 pandemic to evaluate if people hospitalized for noncritical COVID-19 with a history of or a risk factor for CVD were also at an increased risk for cardiac inflammation, Cooper said. The study was stopped early because the pandemic ended. 'The findings were underpowered for efficacy, but they did support a safety signal,' he said. The study found no significant differences in adverse events between the CBD and no-CBD groups. For example, the rate of gastrointestinal disorders was 22.2% in the CBD group and 20.5% in the placebo group. Nervous system disorders were observed in 17.8% of CBD patients vs 18.2% of placebo patients. Eleven percent of CBD patients had respiratory, thoracic, and mediastinal disorders compared with 9% of placebo patients. The rates of cardiac adverse events were also similar between the two groups. No patients in the CBD group vs three (6.8%) of those in the placebo group had tachycardia. One case of atrial fibrillation, cardiac failure, left ventricular hypertrophy, and pericardial effusion was observed in the CBD group vs none in the placebo group. One patient in the placebo group vs none in the CBD group had atrial flutter. Most cases of myocarditis are mild and resolve spontaneously without long-term consequences, Cooper said. However, about 25% of cases have significant cardiovascular sequelae, including arrhythmias and heart failure. 'We know, based on clinical grounds, how to identify those complex patients who are probably going to have a rocky long-term course,' he said. New Treatments Needed While one drug, rilonacept (Arcalyst), has been approved for the treatment of recurrent pericarditis, no approved drugs for myocarditis exist. New treatments are also needed for cardiomyopathy. Bettina Heidecker, MD, head of Heart Failure and Cardiomyopathy at the German Charité Heart Center in Berlin, Germany, told Medscape Medical News , said current therapies such as corticosteroids and other immunosuppressants carry long-term risks such as osteoporosis, metabolic disorders, infections, and organ toxicity, 'A pharmaceutically standardized CBD formulation could offer a targeted anti-inflammatory approach with a more favorable side effect profile,' Heidecker told Medscape Medical News . 'This would be particularly beneficial for younger or lower-risk patients, or those in whom prolonged immunosuppression is problematic.' Heidecker said the new data provide a rationale for continued investigation of CBD in myocarditis and pericarditis. 'It will be exciting to investigate how individual patients respond to CBD, particularly early in the treatment course,' she said. Heidecker and her team in Berlin have been studying the utility of noninvasive magnetocardiography to detect myocardial inflammation and monitor response to anti-inflammatory therapy with the hope that the approach 'may help identify early responders and guide personalized treatment strategies with CBD.' The trial was funded by Cardiol Therapeutics. Cooper is a consultant to Cardiol Therapeutics. Heidecker holds patents for RNA-based diagnostics in myocarditis and holds pending patents on magnetocardiography for diagnosing cardiomyopathy. She reported financial relationships with Biomagnetik Park Hoilding, Pfizer, and AstraZeneca.
