Radha Gopalan, MD
Overall, this is exciting in the sense that for the first time, a trial of this magnitude with about 5,000 patients looked at the nitric oxide pathway in very sick patients with HF who are symptomatic.
The nitric oxide pathway is something that we have been aware of since the 1980s from the very first HF trials. We knew that if patients were on nitric oxide treatment in the initial trials, they did not show a significant benefit with ACE inhibitors.
That was a subject of discussion for the past 25 years. In 2005, the A-HeFT trial was released looking at the nitric oxide pathway — isosorbide dinitrate — in combination with hydralazine in an African-American population, and it showed that there was an additional 15% benefit in mortality.
That was exciting, but the VICTORIA trial patient population is different in that these are very sick patients who have required a hospitalization for decompensated HF. This is an important trial in the timeline of HFrEF. Overall, I would categorize this as exciting and a win with modest results.
With regards to symptomatic hypotension and syncope, this is an area that HF physicians struggle with daily. Yes, it should be carefully looked at because this could become a problem with regard to uptitrating the medication to the target dose of 10 mg daily.
In the VICTORIA trial, about 60% of patients were on triple therapy, which is a good thing. Most patients with HF when they are on triple therapy already have hypotension. When the angiotensin receptor-neprilysin inhibitor came out, we struggled to uptitrate the ARNI to target dose because of the development of hypotension, and this is still an issue. Now we are going to add an additional medicine. While an additional drug is very exciting and encouraging, it also poses difficulty for the clinician to uptitrate and comanage these coexisting medications.
One of the things we would like to see is more of a major impact on mortality benefit. Most of the benefits were derived from a reduction in HF hospitalizations.
Importantly, there is a gender disparity in the patients included in the trial. Only about a quarter of the patients were females, so it’s very hard for us to extrapolate the results. I’m sure the researchers will do some subgroup analyses from this trial in the future. That will give some direction, but it would be nice to have more studies in female patients.
One of the most important areas is that only about 5% of the patients were African Americans. This is a population where the nitric oxide pathway might have a good impact. Future studies probably should examine the effect of vericiguat in the African American population with regard to the influence of the nitric oxide pathway.
One of the good things about this trial is the fact that it was a global trial. About 50% of the patients were from Europe and another quarter from Asia. It was a global study with about 5,000 patients included within a reasonably good period of time. In addition, comorbidities that existed in these patients are similar to what we see in the real world. A fair number of patients had atrial fibrillation, diabetes and hypertension. As a result, this population of patients resembles the patients that I see in the HF clinic, so it’s much easier to adapt the treatment.Radha Gopalan, MDHeart Failure and Transplant Cardiologist
Banner – University Medicine Heart Institute
Read the full article https://www.healio.com/news/cardiology/20200328/victoria-vericiguat-reduces-events-in-highrisk-hf