Do PPIs interact with aspirin?

August 15, 2011

Much ongoing research and discussion concerns the risks of using proton pump inhibitors with clopidogrel.

Key Points

In light of this interaction, it is reasonable to suspect the same problem in connection with aspirin and PPIs. Danish researchers undertook to determine whether PPI use affects the rate of cardiovascular events in patients who are treated with aspirin following initial myocardial infarction (MI). They performed a retrospective nationwide propensity score matched study using administrative data from all Danish hospitals. End points were cardiovascular death, MI, or stroke.

They found that 16.9% of aspirin-treated patients experienced recurrent MI or stroke, or cardiovascular death. Further analysis showed no increase in risk related to use of H2 receptor blockers.

Source: Charlot M, Grove EL, Hansen PR, et al. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: Nationwide propensity score matched study. BMJ. 2011;342:d2690.

Paragraphs 1 and 4 of the foregoing were updated with corrected information September 1, 2011.

Use of rtPA for stroke on the rise

U.S. use of recombinant tissue-type plasminogen activator (rtPA) for stroke is increasing, according to a new study. This drug is the only approved therapy for acute ischemic stroke (AIS).

Researchers used Medicare and pharmacy billing codes to determine percentages of patients who received this treatment at the end of 2005 and 2009. The MEDPAR file and Premier database showed that thrombolytic use increased from 1.1% and 1.4% in 2005 to 3.4% and 3.7% in 2009, respectively. In pharmacy billing records, 3.4% of AIS cases were treated with rtPA in 2009. The 2009 rate increased to 5.2% with inclusion of patients with transient ischemic attack or hemorrhagic stroke who received any thrombolytic as "ischemic stroke patients receiving rtPA."

Therefore 3.4% to 5.2% of AIS patients received thrombolytics in 2009, doubling the rate in 2005. This increase may reflect better awareness of stroke symptoms, meaning that people get to hospitals faster when symptoms begin. To be effective, rtPA must be used within 4.5 hours (ideally within 1 hour) of onset of symptoms.

The authors believed they would find an increase in rtPA use from 2005 to 2009 because of incentives for increased use provided by regulatory agencies and payors. Others attribute the upswing to an increasing number of hospitals that can treat stroke adequately. Because of the possible side effect of hemorrhage, patients at high risk of bleeding may not be candidates for rtPA.

Source: Adeoye O, Hornung R, Khatri P, et al. Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: A doubling of treatment rates over the course of 5 years. Stroke. 2011;42:1952–1955.

Off-label factor VIIa use skyrockets

A new study finds that in the United States, recombinant factor VIIa (rFVIIa) is rarely used for its intended purpose, treatment of bleeding in patients with hemophilia A or B and as an antibody inhibitor against standard-factor replacements.

The drug is far more likely to be used for off-label treatment or prevention of bleeding in conditions such as cardiovascular surgery and body and brain trauma.

The study authors undertook a retrospective evaluation of data from a database of US hospitals. They report that the use of rFVIIa in hospitalized patients without hemophilia grew more than 140-fold from 2000 to 2008. By the end of 2008, 97% of in-hospital use was off-label. Use for the approved indication accounted for only 2.7%.

Another meta-analysis of 64 studies showed that mortality was unaffected by use of rFVIIa among patients in whom it was used for cardiac surgery, body trauma, and intracranial hemorrhage. Thromboembolic events were higher for recipients who underwent cardiac surgery or who had intracranial hemorrhage.

Given the lack of benefit, potential dangers, and cost of $10,000 per dose, these data make a compelling case for education of physicians and pharmacy oversight of use in hospitals.

Sources: Logan AC, Yank V, Stafford RS. Off-label use of recombinant Factor VIIa in U.S. hospitals: Analysis of hospital records. Ann Intern Med. 2011;154:516–522. Yank V, Tuohy CV, Logan AC, et al. Systematic review: Benefits and harms of in-hospital use of recombinant factor VIIa for off-label indication. Ann Intern Med. 2011;154:529–540.

Anna D. Garrett is manager, Outpatient Clinical Pharmacy Programs, Mission Hospital, Asheville, N.C., and president and founder of the National Association of Women in Health Care ( She also is a Drug Topics board member. She can be reached at