Not too many years ago, clinicians who treat patients with heart failure, especially those at high risk for decompensation, lamented what seemed a dearth of new drug therapy options.
Now, with the toolbox brimming with new guideline-supported alternatives, .
Importantly, it entered an especially high-risk population with heart failure and reduced ejection fraction (HFrEF); everyone in the trial had experienced a prior, usually quite recent, heart failure exacerbation.
In such patients, the addition of vericiguat (Merck/Bayer) to standard drug and device therapies was followed by a moderately but significantly reduced relative risk for the trial’s primary clinical endpoint over about 11 months.
Recipients benefited with a 10% drop in adjusted risk (P = .019) for cardiovascular (CV) death or first heart failure hospitalization compared to a placebo control group.
But researchers leading the 5050-patient Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA), as well as unaffiliated experts who have studied the trial, say that in this case, risk reduction in absolute numbers is a more telling outcome.
“Remember who we’re talking about here in terms of the patients who have this degree of morbidity and mortality,” VICTORIA study chair Paul W. Armstrong, MD, University of Alberta, Edmonton, Canada, told theheart.org | Medscape Cardiology, pointing to the “incredible placebo-group event rate and relatively modest follow-up of 10.8 months.”
The control group’s primary-endpoint event rate was 37.8 per 100 patient-years, 4.2 points higher than the rate for patients who received vericiguat. “And from there you get a number needed to treat of 24 to prevent one event, which is low,” Armstrong said.
“Think about the hundreds of thousands of people with this disease and what that means at the public health level.” About one in four patients with heart failure experience such exacerbations each year, he said.
Armstrong is lead author on the 42-country trial’s publication today in the New England Journal of Medicine, timed to coincide with his online presentation for the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC). The annual session was conducted virtually this year following the traditional live meeting’s cancelation due to the COVID-19 pandemic.
The VICTORIA presentation and publication flesh out the cursory top-line primary results that Merck unveiled in November 2019, which had not included the magnitude of the vericiguat relative benefit for the primary endpoint.
The trial represents “another win” for the treatment of heart failure, Clyde W. Yancy, MD, Northwestern University, Chicago, Illinois, said as an invited discussant following Armstrong’s presentation.
“Hospitalization for heart failure generates a major inflection point in the natural history of this condition, with a marked change in the risk for re-hospitalization and death. Up until now, no prior therapies have attenuated this risk, except for more intensive processes and care improvement strategies,” he said.
“Now we have a therapy that may be the first one to change that natural history after a person with heart failure has had a worsening event.”
Interestingly, the primary-endpoint reduction was driven by a significant drop in heart failure hospitalizations, even within a fairly short follow-up time.
“What was fascinating is that the requisite number of events were accrued in less than 12 months — meaning that inexplicably, this is one of the few times we’ve had a trial where the event rate realized was higher than the event rate predicted,” Yancy observed for theheart.org | Medscape Cardiology.
Although the effect size was similar to what was observed for dapagliflozin (Farxiga, AstraZeneca) in DAPA-HF and sacubitril/valsartan (Entresto, Novartis) in PARADIGM-HF, he said, VICTORIA’s population was much sicker and had an “astonishingly high” event rate even while receiving aggressive background heart failure therapy.
It included “triple therapy with renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists in 60% of patients, and at least double therapy in 90% of patients.” Also, Yancy said, 30% of the population had implantable devices, such as defibrillators and biventricular pacemakers.