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- Christopher M. O’Connor, Editor-in-Chief, JACC: Heart Failure∗ ()
- ↵∗Address for correspondence:
Dr. Christopher M. O’Connor, Editor-in-Chief, JACC: Heart Failure, American College of Cardiology, Heart House, 2400 N Street Northwest, Washington, DC 20037.
This year, 2019, has turned out to be a spectacular year for patients with heart failure and the heart failure community. We have seen great breakthroughs, new technologies and therapies, and challenged policies. These may potentially provide patients with better outcomes. The following summarizes my top 5 most influential medical and policy research breakthroughs in the management of patients with heart failure:
1. The DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial was a phase III placebo-controlled randomized trial of 4,744 patients in New York Heart Association (NYHA) functional classes II to IV, with ejection fractions (EFs) of <40%, who received dapagliflozin at 10 mg once a day or placebo in addition to background therapy. Over 18 months, the primary endpoint of worsening heart failure or cardiovascular death was reduced by 26%, (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.65 to 0.85; p < 0.001) in the dapagliflozin group compared with the placebo group. Death from cardiovascular causes occurred in 9.6% in the dapagliflozin group and 11.5% in the placebo group (HR: 0.82; 95% CI: 0.69 to 0.98). This was a breakthrough trial of a new therapeutic class for heart failure with or without diabetes. In particular, the finding that patients without diabetes achieved the same benefit was particularly unique in this trial. These results has afforded great promise for a new class of therapy to add to existing background therapy (1).
2. The PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor [ARNI] With Angiotensin Receptor Blocker [ARB] Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial consisted of 4,822 patients in NYHA functional classes II to IV, with EFs of ≥45%, elevated levels of natriuretic peptide and structural heart disease, who were randomized to sacubitril-valsartan or valsartan therapy. The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. There were 894 primary events in the sacubitril-valsartan group and 1,009 primary events in the valsartan group (rate ratio: 0.87; 95% CI: 0.75 to 1.01; p = 0.06). Cardiovascular death was similar in both groups. NYHA functional class improved, as did the mean change in Kansas City Cardiomyopathy Questionnaire (KCCQ) at 8 months. There was heterogeneity in responses, with a signal of benefit in patients with lower EFs, and in women. The findings of a signal in the lower EF group was consistent with other therapies in this population, and perhaps affords an area of advantage. There was a greater beneficial effect in women compared with than in men. This might reflect the fact that older men with normal EFs are likely to have a higher rate of amyloidosis, which might be refractory to this type of therapy. On reviewing the totality of information from this trial and others, I think there is hope for a therapeutic advantage with this class or other classes of drugs, through the optimal design of clinical trials (2).
3. The PIONEER-HF (Comparison of Sacubitril/valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode) trial consisted of 881 patients with heart failure and reduced EF (HFrEF) who were hospitalized with acute decompensated HF and randomized to receive sacubitril-valsartan or enalapril. The primary endpoint was the average change in N-terminal pro–B-type natriuretic peptide (NT-proBNP) concentration. It was found that there was a significantly greater reduction in the sacubitril-valsartan group than in the enalapril group from baseline in NT-ProBNP through weeks 4 and 8. There appeared to be a reduction in recurrent heart failure events or death. Rates of worsening renal function, hyperkalemia, hypotension, and angioedema did not differ between the 2 groups. This trial provided additional evidence that the initiation of important life-saving therapies (e.g., sacubitril-valsartan) can be initiated safely in the hospital with improvement in the important surrogate endpoint of NT-proBNP, with a trend toward improvement in clinical outcomes (3).
4. The mandatory federal pay-for-performance HRRP (Hospital Readmissions Reduction Program) was created to decrease 30-day hospital readmissions by introducing accountability, as well as improving quality care and coordination in the immediate post-hospitalization phase. Several studies revealed that a reduction in 30-day readmission rates might increase mortality. These investigators believed that the program unfairly penalizes hospitals, particularly safety net hospitals, for issues beyond their control, and has unintended negative consequences due to penalizing readmission over survival. In the position paper published in this issue of JACC: Heart Failure, an analysis presented the pros and cons that argued for a modified policy, which would not reduce safety in hospitals and put greater weight on mortality and patient-reported outcomes as opposed to readmission (4).
5. The recent announcement that the VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF]) trial has met its primary endpoint of reduced heart failure hospitalization or cardiovascular death in patients with HFrEF is the final in my top 5 breakthroughs of 2019. The VICTORIA trial was a randomized, placebo-controlled multicenter double-blind phase III trial of vericiguat, a soluble guanylyl cyclase (sGC) stimulator in 5,050 patients. This new class of therapy, which will be fully evaluated at the American College of Cardiology Scientific Sessions in 2020, may add to our exciting repertoire of therapies being developed for patients with heart failure (5).
It is truly an exciting time in the field of heart failure research. Through changes in policy and the development of new medical therapeutics and policy review, 2019 appears to have been a spectacular year for the promise of our patients.
- 2020 American College of Cardiology Foundation
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