Among patients receiving clopidogrel for coronary artery disease, concomitant therapy with proton pump inhibitors (PPIs) has been associated with an increased risk for recurrent coronary events.
Factores de Riesgo y ENfermedad Arterial (FRENA) is an ongoing, multicenter, observational registry of consecutive outpatients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. We retrospectively examined the influence of concomitant use of PPIs on outcome in patients receiving clopidogrel.
As of March 2009, 1222 patients were using clopidogrel: 595 had coronary artery disease, 329 cerebrovascular disease, and 298 had peripheral artery disease. Of these, 519 (42%) were concomitantly using PPIs. Over a mean follow-up of 15 months, 131 patients (11%) had 139 subsequent ischemic events: myocardial infarction 44, ischemic stroke 40, and critical limb ischemia 55. Seventeen of them (13%) died within 15 days of the subsequent event. PPI users had a higher incidence of myocardial infarction (rate ratio, 2.5; 95% confidence interval [CI], 1.3-4.8), ischemic stroke (rate ratio, 1.9; 95% CI, 1.03-3.7), and a nonsignificantly higher rate of critical limb ischemia (rate ratio, 1.6; 95% CI, 0.95-2.8) than nonusers. On multivariate analysis, concomitant use of clopidogrel and PPIs was independently associated with an increased risk for subsequent ischemic events both in the whole series of patients (hazard ratio, 1.8; 95% CI, 1.1-2.7) and in those with cerebrovascular disease or peripheral artery disease (hazard ratio, 1.5; 95% CI, 1.01-2.4).
In patients with established arterial disease, concomitant use of PPIs and clopidogrel was associated with a nearly doubling of the incidence of subsequent myocardial infarction or ischemic stroke. This higher incidence persisted after multivariate adjustment.
From the *Department of Internal Medicine, Hospital San Pedro de Alcántara, Cáceres, Spain; †Department of Neurology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; ‡Department of Internal Medicine, Hospital Universitario de La Princesa, Madrid, Spain; §Department of Internal Medicine, Hospital Universitari de Bellvitge, Barcelona, Spain; ∥Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; ¶Research Unit, Hospital San Pedro de Alcántara, Cáceres, Spain; and **Department of Internal Medicine, Hospital Santa Maria del Rosell, Cartagena, Spain.
Received for publication February 25, 2010; accepted September 14, 2010.
The authors report no conflicts of interest.
Reprints: Manuel Monreal, MD, PhD, Servicio de Medicina Interna, Hospital Universitari Germans Trias i Pujol, 08916 Badalona (Barcelona), Spain (e-mail: firstname.lastname@example.org).