Key result
Concomitant use of proton pump inhibitors with thienopyridines was associated with an increased risk of ischemic stroke (RR 1.74; 95% CI 1.41-2.16; P<0.001) compared to thienopyridine alone.
Why the study?
Does concomitant use of proton pump inhibitors and thienopyridines increase the risk of ischemic stroke and cardiovascular events compared to thienopyridine alone?
Meta-Analysis (n=131,714)
Does concomitant use of proton pump inhibitors and thienopyridines increase the risk of ischemic stroke and cardiovascular events compared to thienopyridine alone?
Relative Risk: 1.74 (95% CI 1.41–2.16)
p-value: p=<0.001
Co-prescription of proton pump inhibitors and thienopyridines is associated with an increased risk of ischemic stroke and composite cardiovascular events, supporting current guidelines for careful PPI deprescription in these patients.
May increase ischemic stroke risk with thienopyridine-PPI co-use; leaves open confounding versus causality pending dedicated RCTs.
Background and Purpose— Pharmacokinetic and prior studies on thienopyridine and proton pump inhibitors (PPI) coadministration provide conflicting data for cardiovascular outcomes, whereas there is no established evidence on the association of concomitant use of PPI and thienopyridines with adverse cerebrovascular outcomes. Methods— We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies from inception to July 2017, reporting following outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2) combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause mortality, and (6) major or minor bleeding events. After the unadjusted analyses of risk ratios, we performed additional analyses of studies reporting hazard ratios adjusted for potential confounders. Results— We identified 22 studies (12 randomized controlled trials and 10 cohort studies) comprising 131 714 patients. Concomitant use of PPI with thienopyridines was associated with increased risk of ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41–2.16; P <0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI, 1.01–1.29; P =0.04), and MI (risk ratio, 1.19; 95% CI, 1.00–1.40; P =0.05). Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95% CI, 1.04–1.61; P =0.02), composite stroke/MI/cardiovascular death (hazard ratios adjusted, 1.23; 95% CI, 1.03–1.47; P =0.02), but not with MI (hazard ratios adjusted, 1.19; 95% CI, 0.93–1.52; P =0.16). Conclusions— Co-prescription of PPI and thienopyridines increases the risk of incident ischemic strokes and composite stroke/MI/cardiovascular death. Our findings corroborate the current guidelines for PPI deprescription and pharmacovigilance, especially in patients treated with thienopyridines.
No takes yet. Share an insight, caveat, or question.
Malhotra et al. (2018) conducted a meta-analysis in Patients treated with thienopyridines (n=131,714). Proton pump inhibitors (PPI) and thienopyridines vs. Thienopyridine alone was evaluated on Ischemic stroke (RR 1.74, 95% CI 1.41-2.16, p=<0.001). Concomitant use of proton pump inhibitors with thienopyridines was associated with an increased risk of ischemic stroke (RR 1.74; 95% CI 1.41-2.16; P<0.001) compared to thienopyridine alone.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: