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LCZ696 prevented worsening of HF
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CHICAGO — LCZ696 was associated with better prevention of worsening HF compared with enalapril, according to new data from the PARADIGM-HF study.
Initial data from PARADIGM-HF, presented at the European Society of Cardiology Congress in August, demonstrated that LCZ696 (Novartis), which consists of the angiotensin receptor blocker valsartan bonded to the neprilysin inhibitor sacubitril, was superior to ACE inhibition with enalapril for the reduction of death and HF hospitalization in patients with HF and reduced ejection fraction.
New findings presented by John J.V. McMurray, MD, are from analyses of various prespecified measures of nonfatal clinical deterioration. McMurray and colleagues compared 8,399 patients with HF and reduced ejection fraction assigned LCZ696 400 mg per day or enalapril 20 mg per day.
Compared with the enalapril group:
- Fewer patients assigned LCZ696 required intensification of medical treatment for HF (520 vs. 604; HR=0.84; 95% CI, 0.74-0.94).
- Fewer patients assigned LCZ696 required an ED visit for worsening of HF (HR=0.66; 95% CI, 0.52-0.85).
- Patients assigned LCZ696 had fewer hospitalizations for worsening of HF (851 vs. 1,079; P<.001).
- Patients assigned LCZ696 were less likely to require intensive care (768 vs. 879; 18% rate reduction; P=.005).
- Patients assigned LCZ696 were less likely to receive IV positive inotropic agents (31% risk reduction; P<.001).
- Patients assigned LCZ696 were less likely to need implantation of a HF device or a heart transplant (22% risk reduction; P=.07).
In addition, McMurray said, the difference in HF hospitalization rate between the groups was evident at 30 days after randomization, worsening of symptom scores in surviving patients was more common in the enalapril group throughout the study, and the LCZ696 group had a sustained reduction in biomarkers of myocardial wall stress and injury compared with the enalapril group.
“Our conclusions are that compared with enalapril, LCZ696 slows progression of HF and delays or prevents both nonbasal and basal worsening of the condition,” McMurray, from the British Heart Foundation Cardiovascular Research Centre at the University of Glasgow, U.K., said here.
Gregg C. Fonarow
In an invited commentary during the presentation, Gregg C. Fonarow, MD, FACC, FAHA, co-chief of the division of cardiology at UCLA Medical Center, said PARADIGM-HF is “a very successful trial that I think will be able to allow us to really change the approach to managing this important patient population. Should one trial be sufficient to change clinical practice? In this case, given the robust large-scale trial with consistent results, I think the answer is yes.”
He noted that additional trials in real-world populations will be important, and the price of the drug will play a large role in determining its cost effectiveness and value.
“I do believe, should this get through the regulatory process, that LCZ696 will join our other evidence-based HF therapies for those patients with reduced [EF],” Fonarow said. – by Erik Swain
For more information:
McMurray JJV and Fonarow GC. CS.02: Off the Beaten Pathologies. Presented at: American Heart Association Scientific Sessions; Nov. 15-19, 2014; Chicago.
Packer M. Circulation. 2014;doi:10.1161/CIRCULATIONAHA.114.013748.
Disclosure: The study was funded by Novartis. Fonarow and McMurray report no relevant financial disclosures.
Perspective
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Mary Norine Walsh, MD, FACC
I think that the new findings are very interesting. As opposed to the initial published findings, which were regarding survival and hospitalization endpoints, the new findings extend the results … to more patient-centered outcomes, such as doing better with the Kansas City Cardiomyopathy Questionnaire (KCCQ) measures of quality of life. Also, physician-assigned functional class improved. So we now know not only that patients live longer and are hospitalized less, but that they also feel better with this medical regimen.
There is some discussion about the dosage of enalapril that the control group used, so I think we will need some ongoing comparison data looking at the new medication compared with higher-dosed, more conventional medications, including ACE inhibitors. A registry would be ideal, to have both patients who are treated conventionally and those on the new drug, should it be approved by the FDA. In that way, we could continue to gain knowledge and information about the patients who take it and how they do.
On the question of whether the new drug has the potential to change the management of patients with HF, a lot of that will depend on the FDA’s action, but also on how insurance companies will deal with the drug. If it is a medication that is very expensive to patients with regard to co-pay, patients may not be able to have it available to them regardless of the data.
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