Abstract
Objective
Hypertension and type 2 diabetes in combination are associated with a significantly higher level of cardiovascular events. The aim of this prospective study was to evaluate the antihypertensive efficacy and tolerability of single-pill perindopril/indapamide in patients with hypertension and type 2 diabetes.
Design and Methods
Patients with both hypertension and type 2 diabetes were enrolled in this multicenter, prospective, open clinical study. Single-pill perindopril/indapamide was either prescribed on its own (started or switched to from previous treatment) or added to previous therapy. Perindopril/indapamide dosage could be increased, from 5/1.25 mg to 10/2.5 mg once daily, if blood pressure (BP) was uncontrolled. BP and tolerability were assessed at 4 visits over a 6-month period. Microalbuminuria was assessed at baseline and 6 months in a subgroup.
Results
397 patients were analyzed (age 57.6 ± 9.4 years, men 46 %). At baseline, systolic blood pressure (SBP) was 160.0 ± 14.3 mmHg, diastolic blood pressure (DBP) 95.2 ± 8.3 mmHg, and pulse pressure 64.8 ± 12.7 mmHg. Nearly half (45 %) of patients received perindopril/indapamide alone and 55 % added this single-pill combination to existing therapy. After 6 months, SBP fell by 30 mmHg, DBP by 14 mmHg, and pulse pressure by 16 mmHg (all p < 0.0001). SBP was normalized (<140 mmHg) in 84 % of patients who took perindopril/indapamide 5/1.25 mg alone and in 90 % of patients who took perindopril/indapamide 10/2.5 mg alone. Tolerability was rated “good” or “better” by nearly all (99 %) patients. In a microalbuminuria subgroup (n = 59; baseline microalbuminuria 20–200 mg/L; average age 60.5 ± 11.5 years; 28 men [47 %]), there was a significant decrease in SBP (from 160.5 ± 13.9 mmHg to 132.6 ± 12.0 mmHg) and DBP (from 95.3 ± 7.8 mmHg to 81.6 ± 8.4 mmHg) (p < 0.001). Target SBP was reached by 71 % of these patients. Microalbuminuria decreased in 75 % of the subgroup during the follow-up period; levels fell significantly from 45 mg/L (30–88 mg/L) to 30 mg/L (20–50 mg/L) (p < 0.0001).
Conclusion
Treatment with single-pill perindopril/indapamide 5/1.25 or 10/2.5 mg significantly reduced BP, improved BP control, and enhanced kidney protection in patients with hypertension and type 2 diabetes in everyday clinical practice.
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References
Dedov II, Shestakova MV. Diabetes mellitus and arterial hypertension [Russian]. Moscow, Russia: Medical Information Agency; 2006;344.
Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365:1333–46.
Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16:434–44.
Redon J, Martinez F, Nilsson PM. Diabetes, Hypertension, and Insulin Resistance. In: Mancia G, Grassi G, Kjeldsen SE. Manual of hypertension of the European Society of Hypertension. 1st edn. London: Informa Healthcare; 2008.
Pavlova OS, Nechesova TA, Liventseva MM, Korobko I. Medical treatment of arterial hypertension in the Republic of Belarus. Lechebnoye Delo. 2008;3:23–7.
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De BG, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Redon J, Dominiczak A, Narkiewicz K, Nilsson PM, Burnier M, Viigimaa M, Ambrosioni E, Caufield M, Coca A, Olsen MH, Schmieder RE, Tsioufis C, van de Borne P, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Clement DL, Coca A, Gillebert TC, Tendera M, Rosei EA, Ambrosioni E, Anker SD, Bauersachs J, Hitij JB, Caulfield M, De BM, De GS, Derumeaux GA, Erdine S, Farsang C, Funck-Brentano C, Gerc V, Germano G, Gielen S, Haller H, Hoes AW, Jordan J, Kahan T, Komajda M, Lovic D, Mahrholdt H, Olsen MH, Ostergren J, Parati G, Perk J, Polonia J, Popescu BA, Reiner Z, Ryden L, Sirenko Y, Stanton A, Struijker-Boudier H, Tsioufis C, van de Borne P, Vlachopoulos C, Volpe M, Wood DA. 2013 ESH/ESC guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219.
Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, Patel A, Cass A, Neal B, Poulter N, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, MacMahon S, Chalmers J. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol. 2009;20:1813–21.
Ruilope LM, Bakris GL. Renal function and target organ damage in hypertension. Eur Heart J. 2011;32:1599–604.
Tkacheva ON, Barabashkina AV, Novikova IM, Runikhina NK. The study of effects of ramipril and amlodipine combination in patients with arterial hypertension and type 2 diabetes mellitus. Kardiologiia. 2009;49:40–7.
Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317:703–13.
Waeber B, Rotaru C, Feihl F. Position of indapamide, a diuretic with vasorelaxant activities, in antihypertensive therapy. Expert Opin Pharmacother. 2012;13:1515–26.
Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter N, Marre M, Cooper M, Glasziou P, Grobbee DE, Hamet P, Heller S, Liu LS, Mancia G, Mogensen CE, Pan CY, Rodgers A, Williams B. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829–40.
Mancia G, De BG, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A. 2007 ESH-ESC practice guidelines for the management of arterial hypertension: ESH-ESC Task Force on the management of arterial hypertension. J Hypertens. 2007;25:1751–62.
K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43:S1–290.
Nechesova TA, Mitkovskaya NP, Lachimova TI, Lollini VA, Statkevich FM, Dolgoshei TS, Zhdanov AA. Treatment of ambulatory arterial hypertension with a fixed low-dose combination of perindopril/amlodipine: the NOTA study—Noliprel as a first-choice treatment in arterial hypertension. Lechebnoye Delo. 2008;1:12–6.
Ruilope LM, Segura J. Kidney protection: a key target in the management of patients with diabetes. J Hypertens Suppl. 2009;27:S15–8.
Pella D. Efficacy and safety of treatment of hypertensive patients with fixed combination perindopril/indapamide up to 10/2.5 mg: results of the FALCO FORTE programme. High Blood Press Cardiovasc Prev. 2011;18:107–13.
Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, de Boer IH. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24:302–8.
Leoncini G, Viazzi F, Pontremoli R. RAAS inhibition and renal protection. Curr Pharm Des. 2012;18:971–80.
Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887–98.
Ferrari R, Boersma E. The impact of ACE inhbition on all-cause and cardiovascular mortality in contemporary hypertension trials: a review. Expert Rev Cardiovasc Ther. 2013;11:705–17.
Cerezo C, Ruilope LM, Segura J, Garcia-Donaire JA, de la Cruz JJ, Banegas JR, Waeber B, Rabelink TJ, Messerli FH. Microalbuminuria breakthrough under chronic renin-angiotensin-aldosterone system suppression. J Hypertens. 2012;30:204–9.
Garcia-Donaire JA, Segura J, Cerezo C, Ruilope LM. A review of renal, cardiovascular and mortality endpoints in antihypertensive trials in diabetic patients. Blood Press. 2011;20:322–34.
Heerspink HJ, Ninomiya T, Perkovic V, Woodward M, Zoungas S, Cass A, Cooper M, Grobbee DE, Mancia G, Mogensen CE, Neal B, Chalmers J. Effects of a fixed combination of perindopril and indapamide in patients with type 2 diabetes and chronic kidney disease. Eur Heart J. 2010;31:2888–96.
Farsang C. Blood pressure and metabolic efficacy of fixed-dose combination of perindopril and indapamide in everyday practice. Blood Press. 2013;22(Suppl 1):3–10.
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Netchessova, T.A., Shepelkevich, A.P., Gorbat, T.V. et al. Efficacy of Single-Pill Perindopril/Indapamide in Patients with Hypertension and Type 2 Diabetes. High Blood Press Cardiovasc Prev 21, 63–69 (2014). https://doi.org/10.1007/s40292-013-0036-x
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DOI: https://doi.org/10.1007/s40292-013-0036-x