The impact of preadmission oral bisphosphonate use on 30-day mortality following stroke: a population-based cohort study of 100,043 patients

Abstract

Purpose

Bisphosphonate use has been associated with increased risk of fatal stroke. We examined the association between preadmission use of oral bisphosphonates and 30-day mortality following hospitalization for stroke.

Patients and methods

We conducted a nationwide population-based cohort study using medical databases and identified all patients in Denmark with a first-time hospitalization for stroke between 1 July 2004 and 31 December 2012 (N=100,043). Cox regression was used to compute adjusted hazard ratios as a measure of 30-day mortality rate ratios (MRRs) associated with bisphosphonate current use (prescription filled within 90 days prior to the stroke) or recent use (prescription filled in the 90–180 days prior to the stroke). Current use was further classified as new or long-term use.

Results

We found 51,982 patients with acute ischemic stroke (AIS), 11,779 with intracerebral hemorrhage (ICH), 4,528 with subarachnoid hemorrhage (SAH), and 31,754 with unspecified stroke. Absolute 30-day mortality risks were increased among current vs nonusers of bisphosphonates for AIS (11.9% vs 8.5%), ICH (43.2% vs 34.5%), SAH (40.3% vs 23.2%), and unspecified strokes (18.8% vs 14.0%). However, in adjusted analyses, current bisphosphonate use did not increase 30-day mortality from AIS (MRR, 0.87; 95% confidence interval [CI]: 0.75, 1.01); ICH (MRR, 1.05; 95% CI: 0.90, 1.23); SAH (MRR, 1.15; 95% CI: 0.83, 1.61); or unspecified stroke (MRR, 0.94; 95% CI: 0.81, 1.09). Likewise, no association with mortality was found for recent use. Adjusted analyses by type of bisphosphonate showed increased mortality following stroke among new users of etidronate (MRR, 1.40; 95% CI: 1.01, 1.93) and reduced mortality after AIS among current users of alendronate (MRR, 0.87; 95% CI: 0.74, 1.02).

Conclusion

We found no overall evidence that preadmission bisphosphonate use increases 30-day mortality following stroke.

Keywords:

• prognosis
• oral bisphosphonates
• stroke
• mortality
• cardiovascular disease
• osteoporosis treatment

Acknowledgments

The study was supported by the Clinical Epidemiology Research Foundation and the Memorial Foundation of machinery manufacturer Jochum Jensen and wife Mette Marie Jensen, née Poulsen. None of the funding sources had a role in the design, conduct, analysis, or reporting of the study.

Disclosure

BLL is a member of the advisory boards for Merck (MSD), Amgen, Lilly, and UCB. The other authors report no personal conflicts of interest in this work. The Department of Clinical Epidemiology and the Department of Endocrinology and Internal Medicine, Aarhus University Hospital, receive funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies have any relation to the present study.