Use of combination pills with acetylsalicylic acid and clopidogrel in coronary artery disease. Efficacy and assessment of adherence to treatment: Kobra Study

Aim. Assessment of the efficacy and adherence to treatment with acetylsalicylic acid (ASA) and clopidogrel combination drug compared to separate administration of the drugs in patients with acute coronary syndrome and patients with chronic coronary syndrome after coronary stent implantation. Materials and methods. The study included 100 patients randomized to receive either original clopidogrel (Plavix® Sanofi) only or original ASA (Aspirin® Cardio Bayer) only or the generic fixed drug combination (Plagril® A Dr. Reddy's Laboratories Ltd.). Over the first 7–10 days after the index event, all patients were treated with a separate drug in the hospital, then received double antiplatelet therapy with appropriate drugs on an outpatient basis for 4 months, and purchased the drugs on their own for the last 2 months of follow-up. Monitoring the efficacy of therapy and patient adherence to treatment was carried out according to the clinic data, platelet aggregation indicators and blood thromboxane B2 (TXB2), salicylic acid and clopidogrel metabolite (carboxylic acid) levels on the 7th day after disease onset and after 8 and 16 weeks of treatment. Results. Most of the patients were elderly (mean age 68.3±10.6 years), of them 35% were women. After 8 and 16 weeks of treatment in hospital, platelet aggregation indicators did not differ between patients taking separate drugs or a fixed combination. The generic Plagril® A inhibited the aggregation response similarly to the original drugs. At moment of randomization, baseline blood TXB2, salicylic acid and the carboxyl metabolite of clopidogrel levels were comparable in both groups of patients (p>0.05). After 8 weeks of therapy, patients taking Plagril® A had significantly lower TXB2 levels compared with the separate administration of Plavix and Aspirin Cardio: 0.1±0.05 ng/ml vs 0.2±0.23 ng/ml, respectively (p<0.001). After 16 weeks, TXB2 levels reached 0.28±0.56 ng/ml vs 0.43±0.48 ng/ml, respectively (p=0.006). There were no differences in blood salicylic acid and clopidogrel carboxyl metabolite blood levels between the groups of patients during the entire study period. Adherence to antiplatelet therapy during inpatient period of treatment was 100%. In the first 8 weeks, it decreased to 74.5%, and after 16 weeks – to 71.5%. When taking the drugs separately, missing rate was higher in ASA group: 21.2% vs 5% in clopidogrel group. Conclusion. Plagril® A is bioequivalent and as effective as the original ASA and clopidogrel taken separately, in terms of the effect on platelet activity and blood clopidogrel metabolite levels. The adherence to a fixed combination of clopidogrel and ASA in patients with acute coronary syndrome and patients with chronic coronary syndrome is significantly higher than when these drugs are taken separately, both at the stages of free treatment and when purchasing drugs on their own. Keywords: antiplatelet therapy, acetylsalicylic acid, clopidogrel, adherence to secondary prevention, coronary heart disease For citation: Lomakin NV, Buryachkovskaya LI, Senichkina AA, Sumarokov AB, Docenko UV, Kazey VI. Use of combination pills with acetylsalicylic acid and clopidogrel in coronary artery disease. Efficacy and assessment of adherence to treatment: Kobra Study. Consilium Medicum. 2021; 23 (1): 61–69. DOI: 10.26442/20751753.2021.1.200780