OPTIMAL ORGANOPROTECTION, CONTROL OF bLOOD PRESSURE AND METAbOLIC DISORDER  WITH THE FIxED COMbINATION OF LISINOPRIL, AMLODIPINE AND ROSUVASTATIN IN SYSTEMIC  HYPERTENSION

Aim. Evaluation of the ability of the fixed combination of lisinopril, amlodipine and rosuvastatin (Equamer) in achievement of additional angioprotection in patients with systemic arterial hypertension (AH) and high pulse wave velocity (PWV), regardless of previous antihypertensive therapy (AHT).

Material and methods. To the open multicenter observational study 24 weeks duration, 60 patients included, taking double AHT during 6 months. All participants underwent ambulatory 24 hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), pulse wave velocity assessment, laboratory tests (lipids, fasting glucose, insulin resistance index (HOMA), leptin, high sensitive C-reactive protein (hsCRP) before and after transition to the fixed combination of lisinopril, amlodipine and rosuvastatin (Equamer).

Results. By the data from office BP measurement, after transition of patients from the double combinations to fixed combination of lisinopril, amlodipine and rosuvastatin, there was additional decrease of systolic BP (SBP) by 14,3% and diastolic BP (DBP) by 18,5%. By the data from ABPM, decrease of SBP was 16,1%, and DBP — 21,8%. Combination of lisinopril, amlodipine and rosuvastatin decreased PWV by 14,4%, augmentation index by 14,5%, central SBP by 8,1% (p<0,01 for all comparisons with baseline). Fixed combination of lisinopril, amlodipine and rosuvastatin made it to decrease low density lipoproteides by 44%, triglycerides by 36,1% and increase of high density lipoproteides by 10,3% (p<0,01 for all with baseline). Usage of combination of lisinopril, amlodipine and rosuvastatin showed significant decrease of insulin resistance, hsCRP and leptin levels.

Conclusion. Fixed combination of lisinopril, amlodipine and rosuvastatin makes it to better control BP, improve vascular elasticity parameters (augmentation index, PWV, central BP) and facilitates the improvement of lipid and glucose metabolism, decrease of inflammation, leptin resistance in patients taking at baseline double antihypertensive therapy.

1. Whelton PK, Carey RM, Aronow WS, et al. Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension 2017; HYP.0000000000000066. DOI: 10.1161/HYP.0000000000000066.

2. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidemias. Eur Heart J 2016; 37(39):2999-3058. DOI: 10.1093/eurheartj/ehw272.

3. Nemcsik J, Cseprekál O, Tislér A. Measurement of Arterial Stiffness: A Novel Tool of Risk Stratification in Hypertension. Adv Exp Med Biol. 2017; 956: 475-488. DOI: 10.1007/5584_2016_78.

4. Chen X, Huang B, Liu M, Li X. Effects of different types of antihypertensive agents on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials. J Thorac Dis 2015; 7 (12): 2339-47. DOI: 10.3978/j.issn.2072-1439.2015.12.58.

5. Morgan T, Lauri J, Bertram D, Anderson A. Effect of different antihypertensive drug classes on central aortic pressure. Am J Hypertens 2004; 17: 118-23.

6. Mackenzie IS, McEniery CM, Dhakam Z, et al. Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension. Hypertension 2009; 54(2): 409-13. DOI: 10.1161/HYPERTENSIONAHA.109.133801.

7. Elliott WJ, Childers WK. Should beta blockers no longer be considered first-line therapy for the treatment of essential hypertension without comorbidities? Curr Cardiol Rep 2011; 13: 507-16.

8. Hirata K, Vlachopoulos C, Adji A, O’Rourke MF. Benefits from angiotensin-converting enzyme inhibitor ‘beyond blood pressure lowering’: beyond blood pressure or beyond the brachial artery? J Hypertens 2005; 23: 551-6.

9. London GM, Pannier B, Guerin AP, et al. Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease. Comparative effects of ACE inhibition and calcium channel blockade. Circulation 1994; 90: 2786-96.

10. Dhakam Z, McEniery CM, Yasmin A, еt al. Atenolol and eprosartan: differential effects on central blood pressure and aortic pulse wave velocity. Am J Hypertens 2006; 19 (2): 214-9. DOI: 10.1016/j.amjhyper.2005.08.007.

11. Mahmud A, Feely J. Favourable effects on arterial wave reflection and pulse pressure amplification of adding angiotensin II receptor blockade in resistant hypertension. J Hum Hypertens 2000; 14: 541-6.

12. Williams B, Lacy PS, Thom SM, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 2006; 113: 1213-25.

13. Boutouyrie P, Achouba A, Trunet P, Laurent S. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR study. Hypertension 2010; 55 (6): 1314-22. DOI: 10.1161/HYPERTENSIONAHA.109.148999.

14. Matsui Y, O’Rourke MF, Hoshide S, et al. Association between aldosterone induced by antihypertensive medication and arterial stiffness reduction: the J-CORE Study. Atherosclerosis 2011; 215 (1): 184-8. DOI: 10.1016/j.atherosclerosis.2010.12.022.

15. Dahlof B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005; 366: 895-906.

16. Manisty CH, Zambanini A, Parker KH, et al. Differences in the magnitude ofwave reflection account for differential effects of amlodipine- versus atenolol-based regimens on central blood pressure: an Anglo-Scandinavian Cardiac Outcome Trial substudy. Hypertension 2009; 54 (4): 724-30. DOI: 10.1161/HYPERTENSIONAHA.108.125740.

17. Guerin AP, Blacher J, Pannier B. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation 2001; 103 (7): 987-92.

18. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107 (3): 363-9.

19. Yusuf S, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016; 374 (21): 2021-31. DOI: 10.1056/NEJMoa1600176.

20. Ridker PM. Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. N Engl J Med 2008; 359: 2195-207.

21. Roberts ER, Green D, Kadam UT. Chronic condition comorbidity and multidrug therapy in general practice populations: a cross-sectional linkage study. BMJ Open 2014; 4 (7): e005429. DOI: 10.1136/bmjopen-2014-005429.

22. Standards of Medical Care in Diabetes 2017: Summary of Revisions. Diabetes Care 2017; 40 (Suppl. 1): S4-S5. DOI: 10.2337/dc17-S003.

23. Doupis J, Papanas N, Cohen A, et al. Pulse Wave Analysis by Applanation Tonometry for the Measurement of Arterial Stiffness. Open Cardiovasc Med J 2016; 31 (10): 188-95. DOI: 10.2174/1874192401610010188

24. Van Bortel LM, De Backer T, Segers P. Standardization of arterial stiffness measurements make them ready for use in clinical practice. Am J Hypertens 2016. DOI: 10.1093/ajh/hpw084.

25. Cuende JI, Cuende N, Calaveras-Lagartos J. How to calculate vascular age with the SCORE project scales: a new method of cardiovascular risk evaluation. Eur Heart J. 2010; 31 (19): 2351-8. DOI: 10.1093/eurheartj/ehq205.

26. Briasoulis A, Agarwal V, Valachis A, Messerli FH. Antihypertensive effects of statins: a meta-analysis of prospective controlled studies. J Clin Hypertens (Greenwich). 2013; 15 (5): 310-20. DOI: 10.1111/jch.12081.

27. Kario K. Orthostatic hypertension — A new haemodynamic cardiovascular risk factor. Nat Rev Nephrol. 2013; 9: 726-38. DOI: 10.1038/nrneph.2013.224.

28. Ionescu DD. PREFER Investigators. Antihypertensive efficacy of perindopril 5-10 mg/day in primary health care: an open-label, prospective, observational study. Clin Drug Investig 2009; 29 (12): 767-76.

29. Fennessy PA, Campbell JH, Mendelsohn FA, Campbell GR. Angiotensin-converting enzyme inhibitors and atherosclerosis: relevance of animal models to human disease. Clin Exp Pharmacol Physiol 1996; 23 (8): S30-32.

30. Koz C, Baysan O, Yokusoglu M, et al. The effects of perindopril on aortic elasticity and inflammatory markers in hypertensive patients. Med Sci Monit 2009; 15 (7): PI41-5.