Mathematical Modeling for the Effect of Single-Pill Amlodipine and Valsartan Combination Therapy on Biochemical Markers of Atherosclerosis

Objective: The primary aim of this study was to construct a model that could predict the overall effect of concomitant administration of amlodipine and valsartan on biochemical markers of atherosclerosis. Material and Methods: The medical literature was systematically reviewed by searching the PubMed, Embase and Biosis databases using the terms hypertension and ''amlodipine or valsartan'' and ''atherosclerosis or insulin resistance or insulin sensitivity or inflammation''. In total, 39 publications, in which atherosclerotic risk parameters before and after treatment were reported, were identified and included in this analysis. The percentage difference between pre- and post-treatment values was calculated by weighting the values by the number of patients. The additive effect of amlodipine and valsartan was also calculated using a formula postulated on the basis of a previous study. Results: According to the criteria given above, data from 1765 patients from 39 studies were analyzed. The median duration of treatment was 16 weeks (range, 4'156 weeks). Amlodipine and valsartan treatment produced a decrease in HOMA, hsCRP, TNF-alpha and IL-6 levels, and an increase in adiponectin and triglyceride levels. Concomitant use of amlodipine and valsartan is estimated to decrease HOMA, hsCRP, TNF-alpha and IL-6 levels while increasing adiponectin, triglyceride, HDL-C and BMI levels. Conclusion: In conclusion, both amlodipine and valsartan have positive effects on atherosclerotic risk parameters, and the combination of amlodipine/valsartan is predicted to be more effective than either drug administered individually for reduction of atherosclerosis risk, using mathematical modeling. This study provides preliminary results based on mathematical modeling, which need to be confirmed with prospective and controlled clinical studies.