In the JournalsPerspective

PRIME: Sacubitril/valsartan reduces mitral regurgitation

Sacubitril/valsartan reduced mitral regurgitation to a greater extent than valsartan alone in patients with HF and chronic functional mitral regurgitation, according to findings published in Circulation.

The researchers conducted the PRIME double-blind trial of 118 patients (mean age, 63 years; 61% men) with HF with reduced ejection fraction and chronic functional mitral regurgitation secondary to left ventricular dysfunction who were taking standard medical therapy for HF. Patients were assigned valsartan alone or sacubitril/valsartan (Entresto, Novartis) and were assessed via echocardiography.

The primary outcome was change in effective regurgitant orifice area of functional mitral regurgitation at 12 months.

Changes in regurgitant volume, LV end-systolic volume, LV end-diastolic volume and incomplete mitral leaflet closure area served as secondary endpoints.

Compared with the valsartan group, the sacubitril/valsartan group had a greater decrease in effective regurgitant orifice area (–0.058 cm2 vs. –0.018 cm2; P = .032), Duk-Hyun Kang, MD, PhD, from the division of cardiology at Asan Medical Center in Seoul, South Korea, and colleagues wrote.

The sacubitril/valsartan group also had a greater decrease in regurgitant volume vs. the valsartan group (mean difference, –7.3 mL; 95% CI, –12.6 to –1.9), according to the researchers.

Decrease in LV end-diastolic volume index was greater in the sacubitril/valsartan group (mean difference, –7 mL/m2; 95% CI, –13.8 to –0.2), Kang and colleagues wrote, noting that there were no significant differences in other LV metrics, in incomplete mitral leaflet closure area and in changes in BP.

At least one serious adverse event occurred in 12% of patients in the sacubitril/valsartan group and 16% of patients in the valsartan group (P = .54), according to the researchers.

“Angiotensin receptor-neprilysin inhibitor may be considered for optimal medical therapy

of stable patients with heart failure and functional mitral regurgitation,” Kang and colleagues wrote. – by Erik Swain

Disclosures: The study was funded in part by Novartis, which supplied sacubitril/valsartan. The authors report no relevant financial disclosures.

 

Sacubitril/valsartan reduced mitral regurgitation to a greater extent than valsartan alone in patients with HF and chronic functional mitral regurgitation, according to findings published in Circulation.

The researchers conducted the PRIME double-blind trial of 118 patients (mean age, 63 years; 61% men) with HF with reduced ejection fraction and chronic functional mitral regurgitation secondary to left ventricular dysfunction who were taking standard medical therapy for HF. Patients were assigned valsartan alone or sacubitril/valsartan (Entresto, Novartis) and were assessed via echocardiography.

The primary outcome was change in effective regurgitant orifice area of functional mitral regurgitation at 12 months.

Changes in regurgitant volume, LV end-systolic volume, LV end-diastolic volume and incomplete mitral leaflet closure area served as secondary endpoints.

Compared with the valsartan group, the sacubitril/valsartan group had a greater decrease in effective regurgitant orifice area (–0.058 cm2 vs. –0.018 cm2; P = .032), Duk-Hyun Kang, MD, PhD, from the division of cardiology at Asan Medical Center in Seoul, South Korea, and colleagues wrote.

The sacubitril/valsartan group also had a greater decrease in regurgitant volume vs. the valsartan group (mean difference, –7.3 mL; 95% CI, –12.6 to –1.9), according to the researchers.

Decrease in LV end-diastolic volume index was greater in the sacubitril/valsartan group (mean difference, –7 mL/m2; 95% CI, –13.8 to –0.2), Kang and colleagues wrote, noting that there were no significant differences in other LV metrics, in incomplete mitral leaflet closure area and in changes in BP.

At least one serious adverse event occurred in 12% of patients in the sacubitril/valsartan group and 16% of patients in the valsartan group (P = .54), according to the researchers.

“Angiotensin receptor-neprilysin inhibitor may be considered for optimal medical therapy

of stable patients with heart failure and functional mitral regurgitation,” Kang and colleagues wrote. – by Erik Swain

Disclosures: The study was funded in part by Novartis, which supplied sacubitril/valsartan. The authors report no relevant financial disclosures.

 

    Perspective
    Gregg C. Fonarow

    Gregg C. Fonarow

    Sacubitril/valsartan has been demonstrated to reduce CV death and HF hospitalizations superior to that of the ACE inhibitor enalapril in patients with HF with reduced ejection fraction. 

    While a number of HF medications have been effective in reducing functional mitral regurgitation, there are patients that may continue to have functional mitral regurgitation despite receiving these guideline-recommended medications.

    This study finds that compared with the angiotensin receptor blocker valsartan, sacubitril/valsartan was more effective in decreasing the amount of functional mitral regurgitation. This suggests that the augmentation of beneficial vasoactive peptides with neprilysin inhibition facilitates ventricular unloading.

    Sacubitril/valsartan is already class I recommended in national and international HF guidelines to further reduce morbidity and mortality in patients with HF with reduced ejection fraction who are NYHA class II or III. Thus, irrespective of the presence or absence of functional mitral regurgitation, a compelling rationale for treatment with sacubitril/valsartan exists in eligible patients without contraindications.

    Additional studies could evaluate sacubitril/valsartan in patients with functional mitral regurgitation but without HF symptoms to evaluate whether there are clinical benefits including reduced risk for new-onset HF.

    Additional studies to determine the mechanisms accounting for the reduction in functional mitral regurgitation are also warranted.

    • Gregg C. Fonarow, MD
    • Director, Ahmanson-UCLA Cardiomyopathy Center Co-director, UCLA Preventive Cardiology Program Co-chief, Division of Cardiology, UCLA Eliot Corday Chair in Cardiovascular Medicine and Science

    Disclosures: Fonarow reports he consults for Abbott and Novartis.