Proton-pump inhibitors have been prescribed to reduce the gastrointestinal risks of clopidogrel--until a range of small studies suggested that this combination might actually increase the risk of cardiovascular events. The FDA took the unusual step of issuing a warning about the combination, but many people believe the evidence simply doesn't warrant concerns about the combo and may even be putting patients at risk.
Esomeprazole is "at least as bad" as omeprazole in reducing the antiplatelet effects of clopidogrel, a new randomized trial shows, but when it comes to statin effects, SPICE found no differences between rosuvastatin and atorvastatin on platelet function.
Authors of yet another analysis trying to get to the bottom of the real or perceived risk of combining clopidogrel with a proton-pump inhibitor have a new and provocative theory as to just where the signal of increased events may be coming from.
The observation was independent of whether patients carried a gene variant also associated with reduced clopidogrel effectiveness. The findings add yet more observational data to a debate that really could use a solid prospective, randomized trial.
The document recommends the use of proton-pump inhibitors in patients taking thienopyridine antiplatelet agents at high risk of GI bleeding but not in those at low risk; exactly how to define high- and low-risk patients is left to the individual physician.
Patients on dual antiplatelet therapy had a significant reduction in GI events with omeprazole and no increase in cardiovascular events in the first randomized trial of PPI use with clopidogrel. And a new mechanistic study suggests that the clopidogrel-omeprazole interaction may be dose dependent.
Another retrospective analysis, this time in stented patients, shows no significant increases in risk of death, ACS, or stent thrombosis in patients taking concomitant proton-pump inhibitors, mostly pantoprazole. But one expert says no conclusions can be made until the FDA reveals the data it used to decide that a warning was warranted.
UPDATED WITH COMMENTARY // Yet another study suggests increased cardiac events with this combination and that pantoprazole is implicated just as much as other PPIs. But while this study matched patients with propensity scoring, commentators have warned it was still retrospective and therefore will have limitations.
The largest meta-analysis to date on whether treatment with proton-pump inhibitors adversely affects cardiovascular outcomes in patients receiving clopidogrel still provides no firm answers; more research is necessary, say the authors. However, they and other experts conclude that any risk is likely small and that those on clopidogrel with a high likelihood of gastrointestinal bleeding should still receive a PPI.
A new observational study finds a small but statistically insignificant effect of PPIs on the antiplatelet effects of clopidogrel. An accompanying editorialist says the interaction is real but can be limited in clinical practice. However, the previous advice to stagger doses of clopidogrel and PPIs no longer stands, he says, predicting that physicians have not heard the last of this issue.
The FDA has issued a new warning on an interaction between clopidogrel and the PPI omeprazole and other drugs that inhibit the CYP2C19 enzyme, just weeks after the only randomized trial on this issue reported no such interaction.
The randomized controlled trial results should put a stop to alarmist headlines about PPIs blunting efficacy of antiplatelet drugs, experts say. By withholding PPIs, physicians are doing more harm than good, the results suggest.
The use of omeprazole significantly reduced the antiplatelet activity of clopidogrel, even with a high maintenance dose of the drug, and other PPIs, such as pantoprazole, should be preferred in clopidogrel-treated patients, according to investigators.
Data from a second, much smaller study (PRINCIPLE-TIMI 44) show a modest reduction in platelet inhibition with both clopidogrel and prasugrel in patients taking a PPI, but the TRITON results suggest that this is not clinically relevant.
New trial data suggest the H2 antagonist famotidine is effective in the prevention of gastric bleeds in patients taking aspirin, offering a therapeutic alternative to proton-pump inhibitors, say the authors. An accompanying editorialist says that head-to-head trials of the two approaches are needed to determine which is the most effective.
UPDATED // One-year risk of cardiovascular events is 50% higher in patients taking a proton-pump inhibitor on top of clopidogrel and similar for four PPIs, according to a retrospective cohort study of more than 16 700 patients who received clopidogrel poststenting.
UPDATED WITH COMMENTARY // The findings support suspicions that the drug combination diminishes the beneficial effect of the antiplatelet therapy and increases the risk of future events, say researchers. (Juurlink DN et al. CMAJ; published online before print January 28, 2009.)