Expert Review: Valve Disease

Do bisphosphonates slow the progression of aortic stenosis?

Background

Aortic stenosis (AS) in the elderly is commonly associated with leaflet calcification and thickening leading to progressive obstruction of the aortic valve. Calcification has been shown to have a central role in the progression of AS along with inflammation.

Knowledge Gap

Bisphosphonates – drugs that are approved for use in patients with osteoporosis – have been shown to inhibit vascular calcification. Several small observational retrospective studies have shown a possible link between the use of bisphosphonates and slowing of AS progression.

Aim of the Study

In the present study the authors sought to investigate the use of bisphosphonates in a large patient population in order to identify the longitudinal effects of these agents on the progression of AS.

Methods

The present study included 801 female patients older than the age of 60 years (mean age, 76 ±7.6 years) with an aortic valve area (AVA) between 1.0 and 2.0 cm2.

The study was designed as a retrospective case-control study which included patients only if they had follow-up echocardiograms at least a year apart. Primary outcomes were the change in AVA and valvular gradients over time. Mortality and freedom from aortic valve replacement (AVR) were also studied. A propensity-matching method was applied for the probability of the use of bisphosphonates

Results

From the total cohort of 801 patients, 313 (39%) were recieving bisphosphonates and 488 (61%) were not at the time of the first echocardiogram. The mean follow-up time of the study cohort was 5.1±2.4 years, whereas the mean duration of bisphosphonate use was 3.1±2.6 years. The mean ejection fraction at baseline was 56.7±9.6% with a mean AVA of 1.32±0.25 cm2. Peak and mean gradients were 28.4±11 mm Hg and 15.6±6.8 mm Hg, respectively.

In the entire cohort there was a higher rate of change for the first three years, which then stabilized at 0.05cm2 per year after three years. When patients taking bisphosphonates were compared to those who were not, there was no significant difference in the rate of progression of the AVA when change was analyzed over time (p=0.87).

The change in peak and mean gradients was also similar across strata (p=0.75 and 0.43, respectively). Unadjusted analysis comparing survival between the bisphosphonate groups showed no significant difference (p=0.53 and 0.70 for early and late phases of follow-up, respectively).

Occurrence of AVR was not different across bisphosphonate groups (p=0.33 and 0.55 for early and late phases, respectively). Propensity score analysis yielded similar results.

Conclusion

The use of bisphosphonates did not affect the hemodynamic progression of valve stenosis in older women (age > 60 years) with mild-to-moderate stenosis. Furthermore, the use of bisphosphonates did not affect the survival or the rate of AVR during follow-up.

Perspective-Clinical Impact

This study is the largest retrospective analysis to date, and argues against the use of bisphosphonates in older women to prevent the progression of AS.

Some of the strengths of the study included the consideration of a non-linear progression of AS and the use of a propensity analysis rendering the study able to adjust for variables that possibly accelerated the calcification progress (i.e. supplemental calcium or Vitamin D use).

However, the study suffered from certain limitations, such as its retrospective design, not accounting for bisphosphonate compliance, and categorizing different bisphosphonate compound into one group.

Citation: J Am Coll Cardiol 2012; 59:1452-1459, doi:10.1016/j.jacc.2012.01.024

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