Practical efficacy and safety of Konsilar D24 in patients with hypertension: data from the KONSONANS program

Aim. In practice, to evaluate the efficacy, safety and long-term adherence to therapy with a fixed-dose combination of ramipril/indapamide (Konsilar-D24) in patients with grade 1-2 hypertension (HTN) who have not achieved blood pressure (BP) control with prior therapy or have not taken antihypertensive therapy.

Material and methods. This multicenter open-label observational program included 524 patients with grade 1-2 HTN who did not take antihypertensive therapy or did not reach the target BP level with mono or dual antihypertensive therapy, as well as patients shifted to Konsilar-D24 therapy no later than two weeks before the start of the program. All patients signed a written informed consent to participate in the program. The safety analysis set includes all patients who have taken at least one dose of a fixed-dose combination of ramipril/indapamide and have visited physician at least once during the program. The effectiveness analysis set included all patients in the safety population who completed the study in accordance with protocol (n=511). Clinical systolic blood pressure (SBP), diastolic BP (DBP) and heart rate were assessed at baseline, as well as at 0,5, 1, 3 and 6 months of treatment. A post hoc subgroup analysis of changes in BP and heart rate was performed depending on age, sex and baseline body mass index.

Results. The fixed-dose combination of ramipril with indapamide significantly reduced SBP and DBP after 2-week treatment (-20,9±10,1 mm Hg; p

Conclusion. Despite the limitations inherent in observational studies, the KONSONANS program has demonstrated high efficacy and safety of fixed-dose combination of ramipril/indapamide taken once a day in hypertensive patients. Ramipril/indapamide fixed-dose combination therapy significantly improved BP control and achieved even lower individual target BP levels in the majority of hypertensive patients.

1. GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1659-724. doi:10.1016/S0140-6736(16)31679-8.

2. Forouzanfar MH, Liu P, Roth GA, et al. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017;317(2):165-82. doi:10.1001/jama.2016.19043.

3. Shalnova SA, Drapkina OМ. Contribution of the ESSE-RF study to preventive healthcare in Russia. Cardiovascular Therapy and Prevention. 2020;19(3):2602. (In Russ.) doi:10.15829/1728-8800-2020-2602.

4. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet. 2017;389(10064):37-55. doi:10.1016/S0140-6736(16)31919-5.

5. Williams B; Authors/Task Force Members. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36(10):1953- 2041. doi:10.1097/HJH.0000000000001940.

6. Kobalava ZhD, Konradi AO, Nedogoda SV, et al. Arterial hypertension in adults. Clinical guidelines 2020. Russian Journal of Cardiology. 2020;25(3):3786. (In Russ.) doi:10.15829/1560-4071-2020-3-3786.

7. Konradi AO, Nedogoda SV, Nedoshivin AO, et al. Modern antihypertensive therapy: the effectiveness of a unique Russian fixed-dose combination of ramipril and indapamide. Russian Journal of Cardiology. 2020;25(3):3782. (In Russ.) doi:10.15829/1560-4071-2020-3-3782.

8. Frampton JE, Peters DH. Ramipril: an updated review of its therapeutic use in essential hypertension and heart failure. Drugs. 1995;49:440-66. doi:10.2165/00003495-199549030-00008.

9. Witte PU, Walter U. Comparative double–blind study of ramipril and captopril in mild to moderate hypertension. Am J Cardiol. 1987;59:115D-20D. doi:10.1016/0002-9149(87)90065-8.

10. Ruddy MC, Mroczek WJ. Comparison of ramipril and enalapril in patients with essential hypertension. Pharmacotherapy. 1993;13:224-8.

11. Lenox-Smith AJ, Street RB, Kendall FD. Comparison of ramipril against atenolol in controlling mild to moderate hypertension. J Cardiovasc Pharmacol. 1991;18(suppl 2):S150-2.

12. Pfeffer MA, Greaves SC, Arnold JM, et al. Early versus delayed angiotensin–converting enzyme inhibition therapy in acute MI: the healing and early afterload reducing therapy trial. Circulation. 1997;95:2643-51. doi:10.1161/01.cir.95.12.2643.

13. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993;342:821-8.

14. Kjoller-Hansen L, Steffensen R, Grande P. The Angiotensin–converting enzyme inhibition post revascularization study (APRES). J Am Coll Cardiol. 2000;35:881-8. doi:10.1016/s0735-1097(99)00634-8.

15. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin–converting–enzyme inhibitor, ramipril, on cardiovascular events in high–risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145-53. doi:10.1056/NEJM200001203420301.

16. Tu K, Mamdani MM, Jacka RM, et al. The striking effect of the Heart Outcomes Prevention Evaluation (HOPE) on ramipril prescribing in Ontario. CMAJ. 2003;168(5):553-5.

17. Hollander W, Wilkins RW. Chlorothiazide: a new type of drug for the treatment of hypertension. BMQ 1957;8:68-75.

18. Leonetti G, Rappelli A, Salvetti A, et al. Long-term effects of indapamide: final results of a 2-year Italian multicenter study in systemic hypertension. Am J Cardiol. 1990;65:67- 71. doi:10.1016/0002-9149(90)90347-4.

19. Chaffman M, Heel RC, Brodgen RN, et al. Indapamide: a review of its pharmacodynamic properties and therapeutic efficacy in hypertension. Drugs. 1984;28(3):189-235. doi:10.2165/00003495-198428030-00001.

20. Senior R, Imbs JL, Bory M, et al. Indapamide reduces hypertensive left ventricular hypertrophy: an international multicenter study. J Cardiovasc Pharmacol. 1993;22 Suppl 6:S106-S10.

21. Carey PA, Sheridan DJ, de Cordoue A, Guez D. Effect of indapamide on left ventricular hypertrophy in hypertension: a meta-analysis. Am J Cardiol. 1996;77(6):17b-9b. doi:10.1016/s0002-9149(97)89234-x.

22. Ames RP. A comparison of blood lipid and blood pressure responses during the treatment of systemic hypertension with indapamide and with thiazides. Am J Cardiol. 1996;77(6):12b-6b. doi:10.1016/s0002-9149(97)89233-8.

23. Leonetti G, Rappelli A, Salvetti A, Scapellato L. Tolerability and well-being with indapamide in the treatment of mild-moderate hypertension. An Italian multicenter study. Am J Med. 1988;84(1B):59-64.

24. Bataillard A, Schiavi P, Sassard J. Pharmacological properties of indapamide. Rationale for use in hypertension. Clin Pharmacokinet. 1999;37 Suppl 1:7-12. doi:10.2165/00003088-199937001-00002.

25. Bloch MJ, Basile JN. Treating hypertension in the oldest of the old reduces total mortality: results of the Hypertension in the Very Elderly Trial (HYVET). J Clin Hypertens (Greenwich). 2008;10(6):501-3. doi:10.1111/j.1751-7176.2008.08056.x.

26. Balanova YuA, Shalnova SA, Imaeva AE, et al. Prevalence, Awareness, Treatment and Control of Hypertension in Russian Federation (Data of Observational ESSERF-2 Study). Rational Pharmacotherapy in Cardiology. 2019;15(4):450-66. (In Russ.) doi:10.20996/1819-6446-2019-15-4-450-466.

27. Boytsov SA, Balanova YuA, Shalnova SA, et al. Arterial hypertension among individuals of 25-64 years old: prevalence, awareness, treatment and control. By the data from ECCD. Cardiovascular Therapy and Prevention. 2014;13(4):4-14. (In Russ.) doi:10.15829/1728-8800-2014-4-4-14.

28. Chazova IE, Ratova LG, Martynyuk TV. The first results of the Russian study STRATEGY A (a Russian multicenter program to evaluate the effectiveness of Noliprel A forTe in patients with high-risk arterial hypertension with insufficient blood pressure control) — on the way to optimize antihypertensive therapy in patients with high-risk arterial hypertension. Systemic hypertension. 2010;7(4):41-8. (In Russ.) doi:10.26442/SG28898.

29. Krousel-Wood M, Joyce C, Holt E, et al. Predictors of decline in medication adherence: results from the cohort study of medication adherence among older adults. Hypertension. 2011;58(5):804-10. doi:10.1161/HYPERTENSIONAHA.111.176859.

30. Gueyffier F, Cucherat M. The limitations of observation studies for decision making regarding drugs efficacy and safety. Therapie. 2019;74(2):181-5. doi:10.1016/j.therap.2018.11.00