Impact of Proton Pump Inhibitor Treatment On Gastrointestinal Bleeding Associated With Nonsteroidal Anti-inflammatory Drug Use Among Post-myocardial Infarction Patients Taking Antithrombotics: Nationwide Study

Olivia Horga, Mercer University College of Pharmacy

It is suggested that clopidogrel alone, aspirin alone, and a combination of the two is associated with increased risk of gastrointestinal (GI) bleeding. It is also suggested that concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) with antiplatelet therapy increase the risk of GI bleeding. It is proposed that the use of proton pump inhibitors (PPIs) reduces the risk of upper GI bleeding compared with no therapy. It is reported that PPIs are recommended to reduce GI bleeding among patients with a history of upper GI bleeding. They are appropriate in those with multiple risk factors for GI bleeding who require antiplatelet therapy. [1]

The American College of Gastroenterology reports that PPIs are dominant in NSAID-related upper GI injury prophylaxis. It is also suggested that co-therapy with omeprazole was documented to be effective at preventing recurrent ulcer bleeding in NSAID users. [2]

A review of 31 studies suggests that low-dose celecoxib together with a PPI be used for patients who have an increased GI and cardiovascular risks where the GI risk is of greater relevance. It is also suggested that if the cardiovascular risk is of greater concern, then naproxen plus a PPI is favored. [3]

Title: Impact of Proton Pump Inhibitor Treatment On Gastrointestinal Bleeding Associated With Nonsteroidal Anti-inflammatory Drug Use Among Post-myocardial Infarction Patients Taking Antithrombotics: Nationwide Study [4]
Design Cohort, nationwide; N = 82,955
Objective To determine the effect of PPIs on the risk of GI bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs
Study Groups Data collected from all hospitals in Denmark; patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge
Methods Patient information from hospitalization obtained and analyzed
Duration Mean follow-up = 5.1 years
Primary Outcome Measure Gastrointestinal bleeding occurrences, including death from a GI bleed
Baseline Characteristics   Total population

(n = 82,955)

No PPI and no NSAID (n = 68,044) NSAID

(n = 2,006)

PPI

(n = 12,334)

PPI and NSAID

(n = 571)

Mean age, years 67.4 66.7 66.7 71.4 68.7
Male sex, n 53,070 44,802 1,199 6,772 297
Comorbidities
Cardiac arrhythmias, n 7,624 5,821 164 1,590 49
Peripheral vascular disease, n 3,132 2,264 69 776 23
Cerebral vascular disease, n 3,716 2,748 64 878 26
Previous bleeding, n 5,511 3,466 115 1,826 66
Peptic ulcer, n 3,481 1,706 44 1,671 60
Percutaneous coronary intervention, n 32,376 26,764 691 4,725 196
Results Total GI bleeding events: n = 3,229

Incidence rate 0.8 (95% Confidence Interval [CI] 0.7 – 0.8)

Fatal GI bleeding events: n = 282 (8.7 %)
GI bleeding events during NSAID treatment: n = 327;

Incidence rate 2.1 (95% CI 1.8 – 2.4)

Treatment Number of GI bleeding events Hazard ratio (95% CI)
NSAID without PPI n = 267 1.0
NSAID + PPI n = 60 0.72 (0.54 – 0.95)
Adverse Events Common Adverse Events: not reported
Serious Adverse Events: not reported
Percentage that Discontinued due to Adverse Events: deaths from GI bleeding, n = 282 (8.7 %)
Study Author Conclusions This study of a real life cohort of post-myocardial infarction patients taking antithrombotics suggests that use of a PPI diminishes the risk of gastrointestinal bleeding associated with NSAID treatment, regardless of the type of NSAID or PPI prescribed. Consequently, when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might consider prescribing a PPI as well.

The study suggests that use of a PPI diminishes the risk of gastrointestinal bleeding associated with NSAID treatment. [4]

A review of 97 studies indicated that the use of a PPI with clopidogrel might increase the risk of cardiovascular events. It is suggested that PPIs can interfere with clopidogrel metabolism and result in diminished antiplatelet effect. As a result, it is suggested that only patients who have an increased risk of GI bleeding may benefit from the addition of a PPI to their antiplatelet therapy. [1]

When considering whether a patient should receive a PPI with their therapy, risk versus benefit must be considered. If the patient has an increased risk of GI bleeding as a result of also taking NSAIDs, then he or she may benefit from the protection of a PPI.

References

  1. Abraham NS, Hlatky MA, Antman EM, et al. ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation. 2010;122(24):2619-33.
  2. American College of Gastroenterology. http://gi.org/guideline/prevention-of-nsaid-related-ulcer-complications/. Accessed November 9, 2015.
  3. Scheiman JM. The use of proton pump inhibitors in treating and preventing NSAID-induced mucosal damage. Arthritis Res Ther. 2013;15 Suppl 3:S5.
  4. Schjerning olsen AM, Lindhardsen J, Gislason GH, et al. Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study. BMJ. 2015;351:h5096.
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