Management of Hypertension with the Fixed Combination of Perindopril and Amlodipine in Daily Clinical Practice
- 162 Downloads
Current clinical guidelines recognize that the use of more than one agent is necessary to achieve target BP in the majority of patients. The ASCOT-BPLA trial demonstrated that the free combination of amlodipine and perindopril effectively controlled BP and was better than a β-adrenoceptor antagonist (β-blocker)/diuretic combination in reducing total mortality and cardiovascular outcomes.
To evaluate the efficacy and tolerability of a fixed combination of perindopril and amlodipine in the clinical setting.
The STRONG (SafeTy & efficacy analysis of coveRsyl amlodipine in uncOntrolled and Newly diaGnosed hypertension) study was a prospective, observational, multicenter trial.
This was a naturalistic, real-world, clinic-based, outpatient study involving 336 general practitioners/ primary care physicians in 65 cities in India.
Adults aged 40–70 years with newly diagnosed/untreated stage 2 hypertension (BP ≥ 160/100 mmHg), hypertension uncontrolled with monotherapy (BP > 140/90 mmHg), or hypertension inadequately managed with another combination therapy.
Fixed combination perindopril 4 mg/amlodipine 5 mg once daily for 60 days.
Main outcomes measure
The primary outcomes were the mean change in BP from baseline and the proportion of patients achieving adequate BP control (≤ 140/90 mmHg, or ≤ 130/80 mmHg in patients with diabetes mellitus) in the intent-to-treat (ITT) population. Secondary analyses included incidence of adverse events (ITT) and treatment adherence rate (completers).
In total, 1250 patients comprised the ITT population: 32.6% with newly diagnosed hypertension; 40.5% with hypertension uncontrolled with monotherapy; and 26.9% with hypertension inadequately managed with another combination therapy. Mean SBP/DBP decreased significantly from baseline (167.4±15.2/101.4±9.1 mmHg) over 60 days (−41.9 ± 34.8/−23.2 ± 21.8 mmHg; p<0.0001). Target BP was achieved in 66.1% of patients in the total population, 68.3% of untreated patients, 68.4% of patients uncontrolled with monotherapy, and 59.9% of patients inadequately managed with combination therapy. In 161 patients with SBP >180 mmHg at baseline (newly diagnosed: n = 50; uncontrolled on monotherapy: n = 53; inadequately managed on combination therapy: n = 58), BP was reduced by 63.2 ± 32.5/29.0 ± 21.9 mmHg (p<0.0001) at day 60. The fixed combination was safe and well tolerated. All 1175 patients completing the 60-day study (94%) adhered to their treatment regimen.
Fixed combination perindopril/amlodipine was found to be an effective and well tolerated antihypertensive treatment, with an excellent rate of treatment adherence in the clinical setting. Fixed combination perindopril/amlodipine is expected to be useful in the management of hypertension in primary healthcare, with a positive impact on treatment adherence.
KeywordsAmlodipine Perindopril Calcium Channel Antagonist Fixed Combination Quinapril
This study was funded by an administrative grant from Serdia Pharmaceuticals (India) Pvt. Ltd. No other financial consideration was involved and the authors have no conflicts of interest that are directly relevant to the content of this manuscript. Medical writing assistance was provided by Mary Hines, Wolters Kluwer Health.
Agartala A. Chakraborty, D. Chakraborty, J. Chakraborty, R. Debbarma, A. Mandal, S. Sarkar; Ahmedabad N. Suthar; Allahabad B.P. Agarwal, S. Ratna; Ambala A. Baveja, M. Singh; Amritsar S. Dixit, N.S. Sunil; Aurangabad M.B. Anandjiwala, J.S. Avad, S.V. Chandekar, R. Gujrathi, H.R. Tibrewala; Bangalore M.I. Ali, A.P. Bajaj, R. Keerthy, P. Kumar, M.R.K. Murthy, B.R. Prabhakar, V. Prasanna, M.B.S. Raman, B. Rao, C.S. Ravindra, H. Siddappa, B.M. Suraj, G. Suresh, N. Suryaprakash, K. Venkatesh; Bhopal A. Sharma; Bilaspur P. Verma; Calicut K. Bai, A. Krishnan; Chandigarh P. Changedia, A. Gupta; Chennai P.K. Gupta, A. Harish, P. Jaison, G.J. Kumar, R. Leo, N.V.R. Mohan, P. Mohan, A.K. Patwari, K. Premkumar, S. Ramanathan, J. Ramesh, M.M. Ravi, K.M. Shamsuddeen, S. Singhvi, J.S. Sundar, G. Thooyamani, G. Usha; Cochin G. Abraham, J.J. Kannampilly, A.S. Krishnan, P. Ramakrishnan; Coimbatore L.J. Chandra, K. Lakshminarayanan, V.U. Muruganandam, T. Saravanan, S. Sujithkumar; Dehradun A.K. Bhatt, S. Gaikwad, V. Gurung, R. Kumar, A. Rajput; Delhi S. Agarwal, P. Aneja, O.P. Chaddha, S. Dang, A. De, R. Dogra, A.S. Ghai, M.P. Girish, A. Gogna, A.V.S. Gupta, D. Gupta, R. Gupta, D.G. Jain, S.C. Juneja, A.K. Kaushik, R. Khandelwal, G.S. Kochar, H.V. Mahajan, C.M. Malhotra, V. Mehta, C.L. Mittal, S. Mohanty, A. Nigam, L. Patel, A. Rohatgi, H.S. Ruproi, D.P. Sarkar, B. Sharma, R.C. Sharma, C. Shekhar, T.P. Singh, B.K. Tripathi, J.P.S. Tulsi, R.N. Verma, S. Verma; Durgapur S.K. Roy, P. Sadani; Erode R. Gopinath, S.S. Kumar; Faridabad B.K. Prasad; Ghaziabad D.K. Jain; Guntur K. Chakravarty; Gurgaon S. Budhiraja, V.B. Gupta, P. Sahajpal, S.K. Sharma; Guwahati D. Agarwal, T.K. Bhuyan, A.S. Das; Hisar N.K. Khanna; Hyderabad A. Abbas, N. Athaullah, T.S. Babu, Y. Chandrashekhar, K.V.R. Kumar, G. Lakshmi, V.L. Ramachander, T. Ramu, A.V. Rao, K.S. Rao, L.V. Reddy, B.G. Sankar, M. Satyanarayana, M. Sudhir; Indore D. Balani, R. Bhatia, G. Taori; Jabalpur B.K. Behera, S.K. Mishra, N.S. Nim, A. Singh; Jaipur S. Gupta, S. Saxena; Jalgaon S. Patil; Jodhpur M. Balani, R. Chetiwal, S.K. Dadhich; Kalol P.K. Singhal; Kanpur V. Goel, A. Krishna; Kharagpur R. Mohan, S. Roy; Kolhapur J. Patil; Kolkata A.H.S. Ahmed, A. Banerjee, A.K. Banerjee, P.K. Banerjee, C. Batabyal, S. Bhattacharya, P.C. Biswas, S.K. Biswas, S. Chatterjee, A.K. Chaudhuri, A. Das, B.K. Deria, R.K. Dutta, S. Ghosh, T. Ghosh, S. Guha, D. Konar, A. Malhotra, M. Mandal, S. Mandal, S.C. Mandal, B. Mitra, S.C. Mondal, R.D. Mukherjee, A. Pal, A. Parekh, A. Pramanik, A.K. Ray, D. Roy, D. Saha, T.K. Saha, B. Sarkar, M. Sarkar; Kota J.L. Jethwani; Latur S.R. Gatagat, S. Gandhi; Lucknow S. Gupta, S.C. Joshi, A. Kumar, A. Mehrotra, J.N. Mishra, S. Pandey, J. Prasad, H.K. Rastogi; Ludhiana Y. Arora, R. Sharma, R.K. Singla; Madurai C.R.M. Babu, M.K. Daniel, R. Govindarajan; Mangalore R. Bhat, U. Nayak, S.B. Rao, D. Venugopala; Meerut H.M. Rastogi; Mumbai R.K. Advani, S. Anand, R. Anjali, M. Beloskar, P. Bhatia, N. Chandra, V.V. Chandra, S. Doshi, P.S. Gangdev, S. Gautam, R.P. Jain, M. Jalgaonkar, P.S. Kadam, H.R. Kamat, R.M. Kewalramani, T. Koshy, S.H. Kothar, S.N. Mahale, M. Mavani, L. Momania, R.M. Mundada, H. Nanavati, A. Nanaware, S. Nayak, N.J. Padwal, B.M. Parekh, S. Pataria, D. Rajul, N. Redkar, S.K. Sabnis, S.B. Salagre, D. Shah, R.G. Shah, S.J. Shah, A.A. Sharma, R. Singh, R. Teckchandani, H. Thacker, A.Trailokya, S.M. Wani; Mysore P. Kavathe, M.G. Mahesh; Nagercoil J.J. Jerald, R. Mohanadhas, M.C. Nesamony; Nagpur A. Dharaskar, G. Heda; Nashik P.D. Supe; Panjim R. Bhatkurse, A.J. Borkar, T. Coutinho, A. Fernandes, D.L.S. Vas; Patna R.P. Chaudhary, S.N. Jha, R. Kumar, S.K. Pandey, A.K. Pratap, S.S. Shah, S. Singh, N. Sinha, V.K. Thakur; Puducherry K. Narayanan, R. Rajarathinam; Pune A.K. Bhattacharya, A. Bhondwe, S. Bulbule, C. Chivate, V.S. Dharmadhikari, A. Gupta, K. Kavediya, J.V. Mannikar, P.S. Mulay, P. Sengupta, M. Wayal; Raipur M.M. Agrawal, B.B. Solanki, R. Tiwari; Rajkot A.R. Hapani, P. Jethwani, B. Mori, P.P. Rajani, N. Vasavda; Salem K.S.A. Khaddar, P.C.T. Kiruba, V. Ram; Sangroli J.N. Mehta, D.K. Saraswat; Satna A.K. Jain, N. Sharma; Secundrabad A. Bajaj, P.A. Kumar, S.L. Paryani, P.D. Rao; Shimla D. Gupta; Thiruvananthapuram B. Krishnakumar, D.V. Kumar; S.K. Kumar, S.P. Sampath, N.S. Sibi; Trichy M. Prabhukumar, K.M.K. Raj, V. Ravindranath, K. Saravanan, G. Satishkumar, S. Velmurugan; Ujjain S. Khatod, V. Patidar, V. Porwal, S. Rajakumar; Vadodara M.L. Verma; Varanasi W.A. Ansari, K.N. Dwiwedi, M. Gupta, P. Jain, D. Kumar, K.P. Singh; Vijayawada U. Kumar, C.S. Rao, P.V. Satyanarayana, Y. Shivakumar.
- 3.Mancia G, De Backer G, Dominiczak A, 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): 1105–87.PubMedCrossRefGoogle Scholar
- 4.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): 895–906.PubMedCrossRefGoogle Scholar
- 8.National Institute for Health and Clinical Excellence (NICE), British Hypertension Society (BHS). Hypertension: management of hypertension in adults in primary care. 2006 Jun 28 [online]. Available from URL: http://www.nice.org.uk/nicemedia/pdf/CG034NICEguideline.pdf [Accessed 2008 Jan 28].
- 9.Poulter NR, Chang CL, Dahlof B, et al. Evaluating the efficacy of the stepped-care anti-hypertensive strategies used in the Anglo-Scandinavian Cardiac Outcomes Trial BP Lowering Arm (ASCOT) [abstract no. OS11/1]. J Hypertens 2008; 26 Suppl. 1: S10.Google Scholar
- 10.Bertrand M, Sever P. Synergistic effect of perindopril and calcium channel blockers in prevention of cardiac events and death in coronary artery disease patients: analysis from the EUROPA study [abstract no. 3267]. Congress of the European Society of Cardiology (ESC); 2008 Aug 30; Munich.Google Scholar
- 15.Miranda RD, Mion Jr D, Rocha JC, et al. An 18-week, prospective, randomized, double-blind, multicenter study of amlodipine/ramipril combination versus amlodipine monotherapy in the treatment of hypertension: the assessment of combination therapy of amlodipine/ramipril (ATAR) study. Clin Ther 2008 Sep; 30 (9): 1618–28.PubMedCrossRefGoogle Scholar
- 16.Jadhav UM, Bandukwalla SS. Quinapril in systemic hypertension (QUALISH) study [abstract no. P-103]. J Clin Hypertens (Greenwich) 2006; 8 Suppl. A (5): 50.Google Scholar
- 19.Sharma A, Bagchi A, Kinagi SB, et al. Results of a comparative, phase III, 12-week, multicenter, prospective, randomized, double-blind assessment of the efficacy and tolerability of a fixed-dose combination of telmisartan and amlodipine versus amlodipine monotherapy in Indian adults with stage II hypertension. Clin Ther 2007 Dec; 29 (12): 2667–76.PubMedCrossRefGoogle Scholar
- 20.Zannad F, Bernaud CM, Fay R. Double-blind, randomized, multicentre comparison of the effects of amlodipine and perindopril on 24 h therapeutic coverage and beyond in patients with mild to moderate hypertension. General Physicians Investigators’ Group. J Hypertens 1999 Jan; 17 (1): 137–46.PubMedCrossRefGoogle Scholar