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

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.