Effect of Bisphosphonates on the Progression of Degenerative Aortic Stenosis

Abstract

Bisphosphonates appear to regulate mineralization in both bone and vasculature. Degenerative aortic stenosis (AS) is thought to be due to vascular calcification. We studied the effect of bisphosphonates on the progression of degenerative AS. A retrospective study was performed on patients >70 years, who had transthoracic echocardiograms (TTE) >1 year apart and an initial aortic valve area (AVA) of 0.6-2.0 cm². Patients were excluded if they had an ejection fraction <40%, other significant valvular or congenital heart disease, end-stage renal disease or heart transplant. The cohort was divided depending on the use of bisphosphonates. Data were obtained by review of the TTE reports. AVA, peak and mean aortic valve gradient (AVG), and the change between the studies were calculated. Of 4,270 patients screened for AS, 76 patients fit study criteria with 8 in the bisphosphonate group and 68 in the nonbisphosphonate group. The period between the TTEs was 23 ± 5 months in both the groups. AVA in the nonbisphosphonate group worsened by 0.2 cm² and in the bisphosphonate group it improved by 0.1 cm² (P = 0.001 vs. nonbisphosphonate). The changes in peak and mean AVG between groups and compared to baseline were not significant. Bisphosphonates show promise for slowing the progression of degenerative AS.

Mineral metabolism disturbances are associated with the presence and severity of calcific aortic valve disease

“…The effect of osteoporosis therapy has been investigated because of an association between aortic valve calcification and low skeletal bone mineral density (Aksoy et al, 2005). Several small observational studies demonstrated a possible link between use of bisphosphonates and slowing of AVS progression (Skolnick et al, 2009;Sterbakova et al, 2010;Innasimuthu and Katz, 2011), although such beneficial effects may be not remarkable in older women (Aksoy et al, 2012). Taken together, prospective randomized clinical studies are certainly needed to evaluate the role of regulation of calcium and phosphate metabolism for preventing progression of CAVD especially at its early stage.…”

Drug Therapy for Heart Valve Diseases

“…This theory is supported by small retrospective studies reporting delay in loss of valve area 18, 19 . However, in a large retrospective analysis of 801 females (mean age 76 years) with mild to moderate AS, bisphosphonates failed to impact AS progression after >5years 20 ; survival and AVR rate were unaffected over >3 years 20 .…”

Medication Management of Patients Undergoing Transcatheter Aortic Valve Replacement

“…Optimal management strategies depend on AS stage, severity, and symptoms. Options for medical management are limited, as studies have failed to elucidate treatments that retard or reverse disease progression . Despite theoretical concerns with afterload‐reducing agents in patients with symptomatic severe AS, use of these agents has not been shown to compromise cardiac output.…”