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Do Bisphosphonates Slow the Progression of Aortic Stenosis?
Study Questions:
Do bisphosphonates alter the progression of aortic stenosis (AS)?
Methods:
A large echocardiography database was queried for women >60 years old with mild to moderate AS (aortic valve area [AVA] 1.0-2.0 cm2) from 2000-2009. Those without two echocardiograms at least 1 year apart were excluded. Clinical and echocardiographic data were collected, including qualitative AV calcification scores (0-3). Patients were matched using a propensity score for probability of bisphosphonate use.
Results:
Eight hundred and one patients met inclusion criteria; 313 patients (39%) were taking bisphosphonates at the time of index echocardiogram, whereas 488 (61%) were not. Patients who were treated with bisphosphonates were on therapy for 3.1 ± 2.6 years. Comparison of the unmatched cohort showed that baseline comorbid conditions and echocardiographic parameters, including qualitative AV calcification scores, were similar between groups, with the exception of more patients with hyperlipidemia in the bisphosphonate group. There was no change in the rate of progression of AS (calculated AVA, peak/mean gradients) at 1.6-year mean follow-up; no change in survival at 3.1 ± 2.3 years or occurrence of AV replacement (AVR) at 1.5 ± 1.9 years. The results were similar in the propensity-matched analysis. In those who had an AVR during the follow-up period (n = 118), 41 (35%) were taking bisphosphonates. Compared with those who were not, there was no significant difference in disease progression measured by AVA over time. Overall, there appeared to be a nonlinear progression of AS in the entire cohort over time.
Conclusions:
In this retrospective study, the use of bisphosphonates in older women does not appear to be associated with any alteration in the rate of progression of AS, survival, or need for AVR.
Perspective:
Although chronic inflammation and subsequent calcification appear to be causative in the development of AS, available therapies targeting these factors do not appear to be adequate in preventing progression of AS. AS is prevalent and treatment for advanced symptomatic disease in certain patients (e.g., transcatheter aortic valve replacement [TAVR]) has recently become a focus in the cardiovascular medicine community. However, simultaneous investment in advancing our understanding of the underlying pathogenesis of AS, and targeted therapy to prevent progression, should also be a priority.
Keywords: Inflammation, Heart Valve Prosthesis, Follow-Up Studies, Coronary Angiography, Hyperlipidemias, Calcinosis, Diphosphonates, Disease Progression, Echocardiography
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