Circ: PPIs don't increase CV events, death for patients on Plavix

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Proton pump inhibitor (PPI) use does not increase the risk of cardiovascular events or mortality in patients who are administered clopidogrel for a recent MI, no matter the CYP2C19 genotype. However, adverse outcomes were higher in patients who had two loss-of-function alleles, according to FAST-MI registry data published Jan. 24 in Circulation.

Recent studies have found that the CYP2C19 allele can reduce platelet function in patients administered clopidogrel and that PPIs can increase platelet aggregation and can be an independent predictor of high platelet reactivity in those receiving clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis).

Within the FAST-MI (French Registry of Acute-ST-elevation and non–ST-elevation Myocardial Infarction) registry, Tabassome Simon, MD, PhD, from the Hôpital St. Antoinel in Paris and University of Paris, and colleagues analyzed comprehensive data on 3,670 patients who presented with definite MI and received or did not receive either clopidogrel or PPIs. The objective of the analysis was to assess the impact of PPI treatment on the efficacy of clopidogrel therapy.

At the time of enrollment, 2,744 patients were clopidogrel- and PPI-naïve at the index episode—2,353 of those patients received clopidogrel within 48 hours.

The researchers found that the use of PPIs was not associated with the risk of any in-hospital ischemic events. The adjusted odds ratio for death, reinfarction or stroke was reported to be 0.90 in PPI users versus those without PPI. In addition, Simon et al found that continued PPI treatment was not an independent predictor of overall one-year survival in patients treated with clopidogrel or one-year MI, stroke or death.

The researchers also studied the CYP2C19 genotype. Of the 2,353 clopidogrel- and PPI-naïve patients who received clopidogrel within 48 hours, 67 percent contributed a sample to the DNA bank.

The percentage of in-hospital events for patients with and without early PPI treatment was 3.6 percent versus 5.4 percent for those with zero CYP2C19 alleles. The same rate for patients with one or two CYP2C19 variant alleles who were treated with and without early PPI treatment was 3.5 percent versus 4.9 percent and 12 percent versus 5.3 percent, respectively.

In addition, the researchers reported that for those discharged on clopidogrel, one-year death, MI and stroke rates did not differ significantly by PPI use, no matter the genotype.

For those without a loss-of-function allele, the one-year event rate was 9.2 and 8.5 percent for those discharged on PPI versus those not on PPI. The rate for patients with one and two loss-of-function alleles was 5.8 percent versus 6.4 percent and 6.7 and 15.8 percent, respectively.

“Overall, there was no significant interaction between genotype and impact of PPI on the incidence of in-hospital and one-year ischemic events,” the authors wrote.

The researchers also noted that PPI usage did not increase the risk of in-hospital mortality, one-year mortality or in-hospital bleeding in patients receiving clopidogrel. The drug’s use also did not affect MI or stroke-free survival.

“Therefore, because of the low number of patients and resultant large CI ranges, the possibility that a higher early risk may exist in patients with two CYP2C19 variant alleles cannot be dismissed," the authors concluded. “Further large-scale studies incorporating CYP2C19 genotyping to evaluate the influence of PPI use on the clinical response to clopidogrel would be useful to effectively guide therapeutic decisions."