Letter by Potter and Le Lorier Regarding Article, “Cardiovascular Outcomes and Mortality in Patients Using Clopidogrel With Proton Pump Inhibitors After Percutaneous Coronary Intervention or Acute Coronary Syndrome”
To the Editor:
Rassen and colleagues recently reported an analysis of a potentially clinically significant clopidogrel-proton pump inhibitor interaction among patients presenting with acute coronary syndrome or otherwise having undergone a percutaneous coronary intervention based on healthcare claims data.1 We commend the authors of this article and the accompanying editorial2 for their insightful treatment of this issue. Nevertheless, the following points merit further discussion.
First, we were struck by the high proportion of patients who had not filled their clopidogrel prescription within 1 week of hospital discharge, approaching 70% of the overall population studied. After 3 months, only 40% of patients with a clear indication for thienopyridine therapy had filled a prescription for clopidogrel, and only 45% had done so after 6 months. It stands to reason that the clinical impact of 55% to 70% of patients not taking clopidogrel would far outweigh the modest anticipated effect of any interaction with proton pump inhibitors.2 The reasons for such a high rate of noncompliance (or nonprescription) require elucidation because this deficit likely represents an important opportunity for targeted interventions aimed at increasing compliance with a therapy of proven benefit in both percutaneous coronary intervention and acute coronary syndrome.
Second, the British Columbia subpopulation represents more than half of the total population studied. Furthermore, because the Medicare populations are limited to low-income individuals and are subject to an overrepresentation of women, it may well be that the British Columbia population better reflects the spectrum of patients receiving clopidogrel for percutaneous coronary intervention or acute coronary syndrome in current clinical practice. A significant relative risk increase (relative risk=1.64, 95% confidence interval, 1.15 to 2.35) for revascularization after traditional adjustment for confounding (multivariate and propensity score) occurred when the Medicare patients were excluded.1 It is only after a new method of high-dimensional propensity score adjustment3 is applied that this increased risk of revascularization disappears. As such, the authors should discuss the limitations and pitfalls of this new technique with regard to the potential for the introduction of bias and what measures were taken to ensure the validity of the final null result for revascularization in the British Columbia population.
Rassen JA, Choudhry NK, Avorn J, Schneeweiss S. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation. 2009; 120: 2322–2329.
Juurlink DN. Proton pump inhibitors and clopidogrel: putting the interaction in perspective. Circulation. 2009; 120: 2310–2312.