Perindopril for Control of Blood Pressure in Patients with Hypertension and Other Cardiovascular Risk Factors
- 44 Downloads
Background and objectives: Hypertension, one of the major treatable cardiovascular (CV) risk factors, usually occurs in association with other major risk factors. As well as providing rapid blood pressure (BP) goal attainment, antihypertensive therapy should also provide reductions in CV events and mortality in a wide range of patients. For this, higher dosages and combinations of antihypertensive agents are often required. ACE inhibitors are recommended as first-line agents for control of hypertension in patients with additional CV risk factors. The PEACH (Perindopril’s Effect At Controlling Hypertension) study was a community-based study performed to evaluate the effectiveness and safety of highdose perindopril in patients with mild-to-moderate hypertension and additional risk factors for CV disease.
Methods: This was an open-label, multicentre observational study conducted in Canadian general practice clinics. The study assessed the efficacy and tolerability of perindopril given once daily for 10 weeks uptitrated to the maximal recommended dose of perindopril as required for BP control in newly diagnosed or previously treated patients with uncontrolled mild to moderate hypertension and ≥1 additional risk factor. Patients not achieving target BP after 2 weeks of therapy were uptitrated from perindopril 4 mg to perindopril 8 mg once daily. Efficacy endpoints included reduction in systolic (SBP) and diastolic (DBP) BP and BP control. Tolerability assessments included adverse effects and physicians’ assessment of tolerability. The number of missed doses was also recorded.
Results: Overall, 2220 patients with hypertension and ≥1 other risk factor were prescribed perindopril at 291 centres; 51.9% were male, 78.3% Caucasian, 12.8% Asian, 36.2% ≥65 years of age and 34.5% had uncontrolled BP despite previous antihypertensive treatment. Compared with previously treated patients, treatment-naive patients had fewer risk factors, and a higher proportion were Asian (p < 0.05 for all comparisons). Most patients (76%) had 1–2 risk factors. Perindopril produced significant SBP/DBP reductions at 2 and 10 weeks (−15.8/−8.0 and −21.1/−11.0 mmHg, respectively). Overall, at week 10, BP control rate was 53.6%, better than at week 2 in the overall cohort and in all subgroups. Uptitration to high-dose perindopril to achieve BP control was required in 46% of patients with one additional risk factor compared with 64% of patients with ≥4 additional risk factors. These results demonstrate that the more risk factors the patient has, the greater the need for high-dose perindopril to achieve BP control. Perindopril was well tolerated as indicated by the high proportion of physicians (95.9%) reporting ‘good’ to ‘excellent’ tolerability at week 10.
Conclusion: In this community-based clinical practice trial, up to 10 weeks’ perindopril therapy, uptitrated to the maximal recommended dose as required for BP control, significantly reduced SBP/DBP in patients with mild-to-moderate hypertension and additional CV risk factors. Patients with more risk factors were more likely to require high-dose perindopril.
This study was supported by an unrestricted educational grant from Servier. The manuscript was prepared with medical writing assistance from Mary Hines, Vicki Oldfield and Joanne Dalton of Wolters Kluwer Health.
Dr Ogilvie has received honoraria from Servier for participation in workshops and lectures supported by grants from Servier and for his consultative role in the design, analysis and preparation of this manuscript describing the PEACH study and its findings. Dr Anand has received honoraria from Servier for facilitation of continuing medical education events and for his role as coordinator of the PEACH study. The other authors have no financial interests or conflicts of interest that are directly relevant to this study.
PEACH study investigators: E. Schwartz, G. Brouillette, M. Krisdaphongs, C. Riche, S. Ko, M. Leung Sui Fung, G. Barrière, N. Khotianov. L. Kohut, A. Lam, J. Casserly, A. Kopyto, F. Urfer, R. Zarruk, P. Zubkov, M. Faizer, S. Devi, B. Dick, E. Inandan, I. Roitberg, D. Wong, J. Desroches, A. Ahmad, D. Beytell, G. Gatesman, E.J. Pauls, T. Lotfallah, D.E. Hunsberger, M. Ho-Asjoe, K.G. Sie, T. Subramanian, A.W. Carter, J. Goncalves, C. Che, R. Jato-Rodriguez, L. Shimanovsky, D. Yim, A. Razzaque, P. Mehta, K. Bienkowski, Q. Truong, H. William, R. Ciomyk, A. Stern, B.H. Trinh, F. Papadopoulos, S. Rodriguez, P.K Pang, M.L. Van Rooyen, S. Dion, G. Huculak, D.R. Spink, R. Lindzon, D. Norris, S.J. Scala, A.P. Vandenberg, M. Veall, J-M. Martel, I. Lombard, M. Kazimirski, G. Rideout, M.H.M. Tran, V. Martinho, R. Lam, M.S. Parikh, R. Rose, C. Lang, B. Roy, E. Weatherston, P. Wong, D. Lafortune, K. Cho, A. Trevor, N.C. Krayacich, K. Moran De Muller, A. Nayar, J. Morin, C. Guite, P. Diaz, T. Magennis, J.K. Chan, R. Collette, E. Bellavance, C. Nolan, H. Wrobel, A. Trenholm, A. Kuchtaruk, G.S. Meneses, E. Najgebauer, G.G. Marleau, M. Therrien, N. Khoury, M. Lynch, G. Yee, S. Baum, K. Florence, S. Ismail, B.W. King, R. Martins, C. Petrescu, C. Li, S. Nadarajah, N. Chan, M. Csanadi, C. Leung, W. Liang, J. Jacobs, I. Mcleod, P. Patel, Y. Gonzales, C. Levesque, L. Trepanier, G. Roederer, R. Ruest, M. Murray, D. Ciricillo, F. Kuhn, A. Gauthier, G. Marleau, R. Stachula, P.L. Tham, R. Genge, J. Fung, M. Grunebaum, R. Ling, K. Pazuki, A.J. Pinto, S.M. Wu, J. Jadd, E. Vivoda, W. Evans, J. Patel, J. Breton, E. Gaudreau, R. Racine, L. Theriault, R. Goyer, H. Gilani, A. Gabriel, P. Vardy, P. Yong, T.S. Lo, A.G. Csaharyn, D. Duchesne, G.N. Chang, E. Silver, W.A. Lock, R. Luton, S.J. Lombard, R. Prosser, R. Mansour, S. Szarka, M. Look, J. Bobadilla Martinez, H. Crooks, A. Mikhail, K. Woods, N.A. Abell, A. Bredenkamp, G. Roberts, E.J. Osborne, P. Johannsson, H. Lam Poyuen, A. Desjardins, J-J. Legare, A. Studniberg, M.H. Elahi, D. Neal, J-C. Bouchard, P. Morency, P. Richard, H. Lo, E. Osborne, A. Fernandez, W. Tsuchida, E. Arcia-Bravo, G.K. Campbell, W.K. Kan, R. Sandhu, J. Carter, M.J. Chayer, W. Ke, R.A. Ng-A-Fook, S. Belyavskaya, B. Green, F.S. Shoukralla, T. Singh, J. Eastmure, G. Parlan, G. Antoniadis, W. Buckton, J.H.S. Tam, R. Curridor, S.P. Singh, J. Werier, D. Busque, M. Marchand, S. Major, P. Fournier, K. Lummack, Y. Suh, H. Bienkowski, D. Fay, R. Smith, V. Danescu, V. Nair, M. Pather, N. Gill, E. Luke, S. Wu, T. Yoong, C. Bhabba, P. Cameron, M. Ho, M. Keltz, A. Wells, F.B. Forbes, F. Woo, L. Grenier, M. Houde, W. Black, F. Laverdiere, Y. Bricault, P. Liboiron, A.M. Wasfi, G. Ste-Marie, M. Azzopardi, O. Noronha, S. Bardai, P. Chaudhari, S. Vorster, K. Sutherland, L. Sewchand, D. Toffolo, A. Patel-Christopher, J. Vladars, J. Johnson, J. Conradie, S.Y. Lam, A.M. Rossiter, G. Verbonac, S. Ngui, G. Sandhu, D. Rouse, P.S.K. Chan, P. Fingrut, S. Gottesman, S. Kahane, M. Kim, G. Litner, J. Marmina, S. Langford, U. Meham, C. Sandor, M. Mazhar, T. Luk, F. Brisson, J. Charbonneau, J. Collingwood, S. Athar, A. Wade, J. Gaudreau, J. Roy, S. Lachance, V. Oudar, P. Giannakis, P. Sventek, R. Falardeau, B. Macmillan, M.J. Lau, J. Beecroft, J. Black, S. Sidhu, G. Fitzpatrick, W. Leung, D. Meittinen, S. Belyea, Z. Lakhani, B. Wheeler and N. Varma.
- 8.Mancia G, De Backer G, Dominiczak, et al. 2007 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). J Hypertens 2007 Jun; 25(6): 1105–87PubMedCrossRefGoogle Scholar
- 18.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 Sep 10–16; 366(9489): 895–906PubMedCrossRefGoogle Scholar
- 19.Ferrari R. Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome: results of the randomized Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) Study. Arch Intern Med 2006 Mar 27; 166(6): 659–66PubMedCrossRefGoogle Scholar
- 22.Patel A, MacMahon S, Chalmers J, et al. 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 Sep 8; 370(9590): 829–40PubMedCrossRefGoogle Scholar
- 27.Harris SB, Capes SE, Lillie D, et al. Canadian Diabetes Association. 2003 Clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2003 Dec; 27Suppl. 2: S1–S152Google Scholar
- 40.Telejko E. Perindopril arginine: benefits of a new salt of the ACE inhibitor perindopril. Curr Med Res Opin 2007 May 23 (5): 953-60Google Scholar