Interestingly, in the HORIZON-PFT trial, in which an extension from three to 6 years with zoledronic acid was compared to placebo (analysis not included in the aforementioned meta-analyses), a quasi-significant increased risk of stroke was found (3.1% vs 1.5%; p = 0.06) ( Black et al., 2012 ), which suggests a duration-dependent effect that may not be captured by short-term trials.
In the sensitivity analyses: 1) Ever users of oBs showed the same pattern observed in the main analysis: a specific positive association with cardioembolic IS and a clear trend with duration ( Supplementary Table S3 ); 2) the inclusion of prevalent users of oBs made the association to vanish overall (AOR = 1.06; 95% CI:0.89–1.25), even in long-term current users (AOR>1–3 years = 1.14; 95% CI:0.89–1.45 and AOR>3 years = 1.16; 95% CI:0.89–1.53) ( Supplementary Table S4 ). 4