Glycemic control may improve clopidogrel response in patients with stable CAD

SAN DIEGO — In patients with stable CAD, high levels of plasma glucose reduced clopidogrel efficacy, according to data presented at the American College of Cardiology Scientific Sessions.

However, the influence of glucose levels on clopidogrel response was attenuated with the addition of omeprazole to clopidogrel therapy.

For the subanalysis of a double blind trial, researchers evaluated data from 85 patients with chronic stable CAD who were on a daily regimen of aspirin 100 mg. The original study assessed the interaction between clopidogrel and omeprazole or ranitidine. Participants received 1 week of treatment with clopidogrel 75 mg, and were randomly assigned to 1 week of twice-daily omeprazole 20 mg or twice-daily ranitidine 150 mg.

Platelet aggregability was measured in all patients at baseline, after 1 week of clopidogrel and after 1 week of omeprazole or ranitidine. The goal of the subanalysis was to assess the interaction of platelet aggregability at these time points with HbA1c and fasting plasma glucose levels.

The researchers observed significantly greater platelet aggregability among patients with HbA1c levels ≥ 7% (n = 21) compared with HbA1c < 7% (n = 64) at baseline (254.35 PRU vs. 219.04 PRU; P = .036) and after treatment with clopidogrel (190.83 PRU vs. 147 PRU; P = .032). Numerically higher aggregability values were observed among both ranitidine (203.6 PRU vs. 153.17 PRU; P = .073) and omeprazole recipients (184.5 PRU vs. 163.48 PRU; P = .0393) with HbA1c levels ≥ 7% (P for interaction = .753).

In an additional analysis comparing platelet aggregability among patients with fasting plasma glucose above and below 120 mg/dL, platelet aggregability was numerically higher among patients with higher plasma glucose at baseline (249.04 PRU vs. 219.76 PRU; P = .057) and significantly higher after administration of clopidogrel (189.17 PRU vs. 145.11 PRU; P = .019). Higher aggregability was also observed with higher glucose levels after administration of ranitidine (198.75 PRU vs. 147.31 PRU; P = .035), but not omeprazole (179.64 PRU vs. 169.7 PRU; P = .7).

"Glucose control could influence the response to clopidogrel in stable CAD patients," Remo H.M. Furtado, assistant physician at the Heart Institute of the University of São Paulo Medical School in São Paulo, Brazil, told Cardiology Today. The researchers are planning a further study focusing on patients with diabetes to determine whether improved glucose control could improve platelet aggregability.

"In trials of ACS, we have seen that the diabetic subgroup has the greatest benefit with new antiplatelet drugs like ticagrelor and prasugrel," he said. "Antidiabetic drugs have not proven useful at reducing CV events, but we have new drugs on the way ... and we still need to study these drugs to see if the treatment of diabetes itself could improve CV events by this pathway, by improving the control of the response to antiplatelet drugs." – by Adam Taliercio

Reference:

Furtado RHM, et al. Abstract 1122-362. Presented at: American College of Cardiology Scientific Sessions; March 14-16, 2015; San Diego.

Disclosures: Furtado reports receiving research grants from Amgen, AstraZeneca, Cardiorentis, Novartis and Sanofi.