Prescribing PPI and Clopidogrel Together: Current State of Recommendations

Current State of Recommendations

To reduce the risk of gastrointestinal bleeding among patients who
are prescribed mono-antiplatelet or dual-antiplatelet therapy,
clinicians should embrace risk stratification and modification
principles. These include always prescribing the lowest dose of ASA
possible (i.e., 75 or 81 mg daily), as ASA is an independent risk factor
for gastrointestinal bleeding, and carefully assessing individual risk
for antiplatelet-associated gastrointestinal bleeding. A history of
ulcer disease or gastrointestinal bleeding is the greatest risk factor
to predict recurrent gastrointestinal bleeding with an antiplatelet
strategy. However, as the risk of gastrointestinal bleeding increases as
risk factors accumulate, any patient who has more than one risk factor,
such as advanced age; H. pylori infection; or concomitant use
of steroids, anticoagulants, nonsteroidal anti-inflammatory drugs, ASA
or SSRIs, should also be considered a high-risk individual; and
gastroprotection with a PPI is still the best strategy to minimize
gastrointestinal bleeding in high-risk individuals. A 66% reduction in
gastrointestinal bleeding has been demonstrated in an RCT,^[39••] supporting the benefit of PPI gastroprotection over alternatives such as histamine blockers.^[17,67,68]
If a concern exists that the patient may be a poor metabolizer of
clopidogrel, future studies may support the prescription of an
omeprazole alternative such as pantoprazole (which is least dependent on
CYP metabolism) or rabeprazole, which is non-CYP metabolized. However,
the current state of science does not strongly support altering the
choice of PPI among cardiovascular patients on antiplatelet therapy who
require PPI gastroprotection. Finally, the role of pharmacogenomics and
point-of-care testing is being aggressively studied. Results from these
studies will likely challenge the current paradigm for gastroprotection
of cardiovascular patients who require dual-antiplatelet therapy.

Conclusion

The evolution of data over the last 2 years has demonstrated that, when clinical decisions are based on conflicting observational data using surrogate clinical endpoints, incorrect assumptions regarding drug interactions are made. The publication of the COGENT trial has highlighted the importance of randomized controlled data to support the use of PPI gastroprotection in patients co-prescribed clopidogrel. A multidisciplinary consensus document highlights a risk–benefit assessment strategy for all patients prescribed clopidogrel and recommends PPI gastroprotection for those at highest risk of gastrointestinal bleeding as they are most likely to benefit from the marked reduction in gastrointestinal bleeding risk. Further characterization of the genetic variation in both PPI and clopidogrel drug metabolism should help elucidate the subset of cardiac patients in whom PPI prescription may be disadvantageous.