How PPI, Thienopyridine Combined Use Impact Cerebrovascular Outcomes

Currently, prior studies on thienopyridine and proton pump inhibitor (PPI) co-administration provide conflicting data for cardiovascular outcomes. However, because there is no evidence on the association of combined use of PPI and thienopyridines with adverse cerebrovascular outcomes. Researchers sought to assess these cerebrovascular outcomes for a study in Stroke.

• A systemic review of 22 studies—12 randomized controlled trials and 10 cohort studies—comprised of 131,714 patients was conducted.
• The researchers assessed 6 outcomes among patients treated with thienopyridine and PPI versus thienopyridine alone. The outcomes included ischemic stroke, combined ischemic or hemorrhagic stroke, composite outcome of stroke, myocardial infarction (MI), and cardiovascular death, MI, all-cause mortality, and major or minor bleeding events.
• A co-prescription of PPI and thienopyridines was associated with an increased risk of ischemic stroke, composite stroke/MI/cardiovascular death, and MI.
• In an adjusted analysis, use of both PPI and theinopyridines was also associated with increased risk of stroke, composite stroke/MI/cardiovascular death. However, the risk of MI alone did not increase.

To better understand why a co-prescription of PPI and theinopyridines increases the risk of stroke among patients, Konark Malhotra, MD, department of neurology, Charleston Area Medical Center, and lead study author, recently discussed the findings of his study, and explained what a pharmacist can do if they receive a co-prescription from a patient. 

Author Insights

What should a pharmacist do if they receive a co-prescription of PPI and thienopyridines?

Pharmacist should a) notify the physician of decreased efficacy of thienopyridine when co-administered with PPI, b) recommend deprescription of PPIs i.e. dose reduction with a goal to taper off completely after minimum intended duration, and c) pharmacovigilance for co-prescription of these medications.

Is there an appropriate replacement for a prescription of a PPI for patients who are treated with thienopyridines? Will this lessen the risk of strokes or other cerebrovascular adverse outcomes? 

Histamine blockers aka H2 blockers would be a better option for patients who are already on thienopyridines. However, future trials need to confirm the safety of such combined prescriptions.

What is the best way to taper the usage of PPI’s in patients treated with thienopyridines, if necessary?

Physicians should aim for minimum intended duration of PPI use for patients already on thienopyridine. If GI bleeding risk is high or prolonged duration of gastroprotection is needed, recommendation should be either switch to H2 blockers.

Additionally, deprescription remains the best strategy in the patients who are co-prescribed on thienopyridines and PPIs.  

Was the risk of stroke higher or lower than you expected among patients? 

The risk of stroke was higher than we expected among patients co-prescribed on thienopyridines and PPIs.

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