胸やけの薬は虚血性脳卒中リスクを上昇させる可能性がある(EP.AOS.765, Presentation 391)

プロトンポンプ阻害薬は虚血性脳卒中リスクを上昇させる可能性がある
Proton pump inhibitors may increase risk of ischemic stroke
プロトンポンプ阻害薬（PPI）は虚血性脳卒中リスクを上昇させる可能性がある、との予備研究の結果が2016年American Heart Association学術集会で発表された。研究者らは、平均年齢57歳のデンマーク人患者244,679人のカルテを解析した。PPI（オメプラゾール、pantoprazole、ランソプラゾール、またはエソメプラゾール）内服患者においては、全体の脳卒中リスクが21%上昇した。最も低用量のPPIでは、脳卒中リスクは軽度上昇、または上昇しなかった。最高用量では、ランソプラゾールの30%からpantoprazoleの94%までの脳卒中リスク上昇を認めた。ファモチジンやラニチジンなどのH2ブロッカーでは、脳卒中リスクは上昇しなかった。
Full Text

A popular group of antacids known as proton pump inhibitors, or PPIs, used to reduce stomach acid and treat heartburn may increase the risk of ischemic stroke, according to preliminary research presented at the American Heart Association's Scientific Sessions 2016.

"PPIs have been associated with unhealthy vascular function, including heart attacks, kidney disease and dementia," said Thomas Sehested, M.D., study lead author and a researcher at the Danish Heart Foundation in Copenhagen, Denmark. "We wanted to see if PPIs also posed a risk for ischemic stroke, especially given their increasing use in the general population."

Researchers analyzed the records of 244,679 Danish patients, average age 57, who had an endoscopy. During nearly six years of follow up, 9,489 patients had an ischemic stroke for the first time in their lives. Researchers determined if the stroke occurred while patients were using 1 of 4 PPIs:  omeprazole, pantoprazole, lansoprazole, and esomeprazole.

For ischemic stroke, researchers found:

  • Overall stroke risk increased by 21 percent when patients were taking a PPI.
  • At the lowest doses of the PPIs, there was slight or no increased stroke risk.
  • At the highest dose for these 4 PPI's, stroke risk increased from 30 percent for lansoprazole to 94 percent for pantoprazole.
  • There was no increased risk of stroke associated with another group of acid-reducing medications known as H2 blockers, which include famotidine and ranitidine.

In comparison with non-users, PPI users were older and had more health conditions, including atrial fibrillation at baseline (3.4 vs. 3.8 percent). The study accounted for age, gender and medical factors, including hypertension, atrial fibrillation, heart failure and the use of certain pain relievers that have been linked to myocardial infarction and stroke.

Authors believe that their findings, along with previous studies, should encourage more cautious use of PPIs.

"At one time, PPIs were thought to be safe, without major side effects," he said, "This study further questions the cardiovascular safety of these drugs."

Although their study did not find a link between H2 blockers and stroke, the authors could not say that this group of drugs would be better for patients than PPIs.

Doctors prescribing PPIs, should carefully consider whether their use is warranted and for how long: "We know that from prior studies that a lot of individuals are using PPIs for a much longer time than indicated, which is especially true for elderly patients."

Study limitations include its observational design, which cannot establish cause and effect, and the fact that nearly all the participants were white. Authors believe that a randomized controlled trial of PPIs and cardiovascular disease is warranted.
Co-authors are Emil L. Fosbøl, M.D., Ph.D.; Peter W. Hansen, M.D.; Mette G. Charlot, M.D., Ph.D.; Christian Torp-Pedersen, M.D., DMSc.; and Gunnar H. Gislason, M.D., Ph.D.

This study was funded by the Danish Heart Foundation.