Possible drug interaction between clopidogrel and ranitidin or omeprazole in patients with stable coronary artery disease: a comparative study

BACKGROUND: Proton-pump inhibitors (PPIs) are often prescribed to patients taking dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and clopidogrel. However, this class of medication, especially omeprazole, has been associated with a reduction of clopidogrel efficacy, leading many to substitute omeprazole with ranitidine. METHODS: The present study analyzed patients with stable coronary artery disease (CAD) in use of ASA 100 mg daily. Platelet aggregability was measured at baseline and after one week of clopidogrel 75 mg daily. Then, the subjects were randomized, in a double-blinded, doubledummy fashion, to omeprazole 20 mg twice a day or ranitidine 150 mg twice a day. After one more week, aggregability tests were repeated. Platelet aggregability was evaluated by the following methods: VerifyNow P2Y12TM (Accumetrics - San Diego, California, USA, main endpoint of the study), with aggregability depicted as percent Inhibition of Platelet Aggregation (IPA) and as P2Y12 Reactivity Units (PRU); whole blood aggregometry by bioimpendance using ADP and collagen with aggregability measured in Ohms; and Platelet Function Analyser 100TM (Siemens Healthcare Diagnostics, Newark, Delaware, USA) using collagen/ADP cartridge with aggregability measured in time to closure in seconds. Besides that, serum thromboxane B2 dosage was done on the last visit to evaluate ASA effect. RESULTS: Eighty-five patients were included in final analysis (41 in the omeprazole group and 44 in the ranitidine group). IPA was significantly decreased after addition of omeprazole (from 26.3% ± 32.9 to 17.4% ± 33,1; P = 0.025), with no significant changes being observed in the ranitidine group (from 32.6% ± 28.9 to 30.1% ± 31.3; P = 0.310). When taking into account PRU values, there was a numerical, but statistically non-significant increase in the omeprazole group (from 159.73 ± 83.06 to 173.54 ± 72.29; P = 0.116), with a very slight difference in the ranitidine group (from 153.61 ±...