Taking PPIs, thienopyridines together tied to higher cerebrovascular risk

Last Updated: 2018-02-02

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Co-prescription of proton pump inhibitors (PPIs) and thienopyridines is associated with an elevated risk of adverse cerebrovascular events, according to a new systematic review and meta-analysis.

"Our study shows that co-administration of PPIs and thienopyridines increases the risk of adverse cerebrovascular outcomes including ischemic stroke, combined ischemic and hemorrhagic stroke, and combined stroke/MI/cardiovascular death," Dr. Konark Malhotra of West Virginia University in Charleston told Reuters Health by email.

"Physicians should aim for a minimum intended duration of PPI use - i.e., deprescription of PPIs among patients who require treatment with thienopyridines. If gastrointestinal bleeding risk is high or prolonged duration of gastroprotection is needed, switching to histamine blockers would be a better option for patients already on thienopyridines. However, future trials need to confirm the safety of such combined prescriptions," he advised.

"Pharmacists should follow pharmacovigilance for coprescription of thienopyridines and PPIs," Dr. Malhotra added. "They should notify the physician regarding decreased efficacy of thienopyridines when co-administered with PPI; and they should recommend deprescription of PPIs; i.e., dose reduction with the goal to taper off completely after minimum-intended-duration use."

Dr. Malhotra and colleagues searched the literature for randomized controlled trials and cohort studies including patients treated with thienopyridine and PPI versus thienopyridine alone up until July 2017. They identified 12 randomized controlled trials and 10 cohort studies with a total of more than 131,700 participants.

In adjusted analyses, using PPI with thienopyridines was associated with significantly increased risks of stroke (hazard ratio, 1.30; P=0.02) and composite stroke/MI/cardiovascular death (hazard ratio, 1.23; P=0.02), but not MI (hazard ratio, 1.19; P=0.16), the researchers report in Stroke, online January 16.

"It was essential to perform this study as no prior studies have highlighted the increased risk of adverse cerebrovascular outcomes with co-prescription of PPI and thienopyridines. Additionally, prior study data for adverse cardiovascular outcomes for this coprescription have been conflicting," Dr. Malhotra told Reuters Health.

Dr. Lee H. Schwamm, vice chair of the department of neurology at Massachusetts General Hospital in Boston, told Reuters Health by email, "Many patients are on these medications. The study raises the important issue of whether or not patients who require a specific class of antiplatelet medications should avoid use of PPIs, as these medications may interfere and reduce effectiveness of medicines like clopidogrel."

"This question has been raised before and prior studies have not found conclusive evidence of an effect across populations," noted Dr. Schwamm, who was not involved in the new research. "It is unclear if the methods used in this paper introduce unintended bias. It might be that people who need both classes of these medicines are at greater risk for other reasons, and so the risk is not due to the medications (PPI) but to the underlying pathology."

"Also, there is no access to patient-level data, so even though the authors try to do adjusted analyses, they are inherently very limited," he cautioned.

"The study raises the possibility that this is a true finding but it cannot be viewed as a definitive finding," Dr. Schwamm said. "However, a definitive study may be difficult to fund and conduct, so I would encourage the authors to persuade the study investigators of these trials to provide patient-level data from these trials and pool them for a large patient-level meta-analysis, which would allow for more powerful adjusted analyses."

"In the absence of other data, I would recommend that providers avoid co-prescribing these two classes of medications if an alternative prescription is equally effective," he concluded. "However, if both classes of medicines are needed, it is very reasonable to continue providing them together."

SOURCE: http://bit.ly/2DTjK5b

Stroke 2018.