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Combination of Amlodipine plus Angiotensin Receptor Blocker or Diuretics in High-Risk Hypertensive Patients

A 96-Week Efficacy and Safety Study

  • Original Research Article
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American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background and Objectives

Antihypertensive therapy is effective in reducing the risk of major adverse cardiovascular events. However, blood pressure (BP) control rate remains poor and the optimal combination therapy against hypertension is not established in China. The objective of this study was to evaluate the long-term efficacy and safety of two antihypertensive regimens, amlodipine plus telmisartan and amlodipine plus amiloride/hydrochlorothiazide, in patients with essential hypertension and at least one cardiovascular risk factor.

Methods

In a multicenter open-label clinical trial, eligible patients were randomized to receive treatment with amlodipine 2.5–5 mg plus amiloride/hydrochlorothiazide 1.25–2.5 mg/12.5–25 mg (Group A) or amlodipine 2.5–5 mg plus telmisartan 40–80 mg (Group T). If a target BP was not reached, other antihypertensive agents would be added. The target BP was <130/80mmHg for patients with diabetes mellitus or chronic kidney disease and <140/90mmHg for others. Efficacy variables were changes from baseline in systolic BP and diastolic BP at the endpoint of 96 weeks. Safety evaluations included monitoring of any adverse events (AEs).

Results

Of 13 542 patients randomized, 13 080 (96.6%) completed the study: 6529 in Group A and 6551 in Group T. At endpoint, the BP levels were reduced by 27.4/14.3 mmHg in Group A and 27.1/14.5 mmHg in Group T. The BP control rates were similar for the two therapeutic regimens (87.5% vs 86.1%). Less than 4% of patients in each group discontinued their drugs during follow-up. Peripheral edema was one of the most common AEs, and occurred in only 24 patients in Group A and 19 in Group T.

Conclusions

Long-term combination therapy with amlodipine plus telmisartan or amlodipine plus amiloride/hydrochlorothiazide was not only well tolerated but also efficacious in reducing BP levels with acceptable control rates in the majority of hypertensive patients.

Clinical Trials Registration

ClinicalTrials.gov number NCT01011660.

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References

  1. Wang L. 2002 National Nutrition and Health Survey: Report I [in Chinese], general report. People’s Medical Publishing House: Beijing, 2005.

    Google Scholar 

  2. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA 2003; 289 (19): 2560–72.

    Article  PubMed  CAS  Google Scholar 

  3. Lopatriello S, Berto P. Long-term social costs of hypertension. Expert Rev Pharmacoeconomics Outcomes Res 2003; 3 (1): 33–40.

    Article  Google Scholar 

  4. Zhang XH, Lu ZL, Liu L. Coronary heart disease in China. Heart 2008; 94 (9): 1126–31.

    Article  PubMed  Google Scholar 

  5. Liu M, Wu B, Wang WZ, et al. Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol 2007; 6 (5): 456–64.

    Article  PubMed  Google Scholar 

  6. Liu L. Cardiovascular diseases in China. Biochem Cell Biol 2007; 85 (2): 157–63.

    Article  PubMed  Google Scholar 

  7. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338: b1665.

    Article  PubMed  CAS  Google Scholar 

  8. Wolf-Maier K, Cooper RS, Kramer H, et al. Hypertension treatment and control in five European countries, Canada, and the United States. Hypertension 2004; 43 (1): 10–7.

    Article  PubMed  CAS  Google Scholar 

  9. Wu Y, Huxley R, Li L, et al., China NNHS Steering Committee; China NNHS Working Group. Prevalence, awareness, treatment, and control of hypertension in China: data from the China National Nutrition and Health Survey 2002. Circulation 2008; 118 (25): 2679–86.

    Article  PubMed  Google Scholar 

  10. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288 (23): 2981–97.

    Article  Google Scholar 

  11. Dahlöf B, Sever PS, Poulter NR, et al., ASCOT Investigators. 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 (9489): 895–906.

    Article  PubMed  Google Scholar 

  12. Jamerson K, Weber MA, Bakris GL, et al., ACCOMPLISH Trial Investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008; 359 (23): 2417–28.

    Article  PubMed  CAS  Google Scholar 

  13. 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; 25 (6): 1105–87.

    Article  PubMed  CAS  Google Scholar 

  14. Gong L, Zhang W, Zhu Y, et al. Shanghai Trial of Nifedipine in the Elderly (STONE). J Hypertens 1996; 14 (10): 1237–45.

    Article  PubMed  CAS  Google Scholar 

  15. Wang JG, Staessen JA, Gong L, et al. Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group. Arch Int Med 2000; 160 (2): 211–20.

    Article  CAS  Google Scholar 

  16. Liu L, Zhang Y, Liu G, et al., FEVER Study Group. The Felodipine Event Reduction (FEVER) study: a randomized long-term placebo controlled trial in Chinese hypertensive patients. J Hypertens 2005; 23 (12): 2157–72.

    Article  PubMed  CAS  Google Scholar 

  17. Hashimoto J, Hirayama H, Hanasawa T, et al. Efficacy of combination antihypertensive therapy with low-dose indapamide: assessment by blood pressure self-monitoring at home. Clin Exp Hypertens 2005; 27 (4): 331–41.

    PubMed  CAS  Google Scholar 

  18. Littlejohn 3rd TW, Majul CR, Olvera R, et al., Study Investigators. Results of treatment with telmisartan-amlodipine in hypertensive patients. J Clin Hypertens (Greenwich) 2009; 11 (4): 207–13.

    Article  CAS  Google Scholar 

  19. Littlejohn 3rd TW, Majul CR, Olvera R, et al., Study investigators. Telmisartan plus amlodipine in patients with moderate or severe hypertension: results from a subgroup analysis of a randomized, placebo-controlled, parallelgroup, 4×4 factorial study. Postgrad Med 2009; 121 (2): 5–14.

    Article  PubMed  Google Scholar 

  20. White WB, Littlejohn TW, Majul CR, et al. Effects of telmisartan and amlodipine in combination on ambulatory blood pressure in stages 1–2 hypertension. Blood Press Monit 2010; 15 (4): 205–12.

    Article  PubMed  Google Scholar 

  21. Wang W, Ma L, Zhang Y, et al. The combination of amlodipine and angiotensin receptor blocker or diuretics in high-risk hypertensive patients: rationale, design and baseline characteristics. J Hum Hypertens 2011; 25 (4): 271–7.

    Article  PubMed  CAS  Google Scholar 

  22. Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. Blood Press 2009; 18 (6): 308–47.

    Article  PubMed  CAS  Google Scholar 

  23. Calhoun DA, Crikelair NA, Yen J, et al. Amlodipine/valsartan/hydrochlorothiazide triple combination therapy in moderate/severe hypertension: secondary analyses evaluating efficacy and safety. Adv Ther 2009; 26 (11): 1012–23.

    Article  PubMed  Google Scholar 

  24. Black HR, Elliott WJ, Grandits G, et al., CONVINCE Research Group. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA 2003; 289 (16): 2073–82.

    Article  PubMed  CAS  Google Scholar 

  25. Li H, Meng Q, Sun X, et al. Prevalence, awareness, treatment, and control of hypertension in rural China: results from Shandong Province. J Hypertens 2010; 28 (3): 432–8.

    Article  PubMed  CAS  Google Scholar 

  26. Ong KL, Cheung BM, Man YB, et al. Prevalence, awareness, treatment, and control of hypertension among United States adults 1999–2004. Hypertension 2007; 49 (1): 69–75.

    Article  PubMed  CAS  Google Scholar 

  27. Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA 2010; 304 (1): 61–8.

    Article  PubMed  CAS  Google Scholar 

  28. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010; 362 (17): 1575–85.

    Article  PubMed  Google Scholar 

  29. Smith TR, Glazer RD, Koren MJ, et al. Combination therapy with amlodipine/valsartan in essential hypertension: a 52-week, randomised, open-label, extension study. Int J Clin Pract 2010; 64 (10): 1367–74.

    Article  PubMed  CAS  Google Scholar 

  30. Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension. Clin Ther 2007; 29 (4): 563–80.

    Article  PubMed  CAS  Google Scholar 

  31. Philipp T, Glazer RD, Zhao Y, et al. Long-term tolerability and efficacy of the combination of amlodipine/valsartan in hypertensive patients: a 54-week, open-label extension study. Curr Med Res Opin 2009; 25 (1): 187–93.

    Article  PubMed  CAS  Google Scholar 

  32. Fogari R, Malamani GD, Zoppi A, et al. Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. J Hum Hypertens 2003; 17 (3): 207–12.

    Article  PubMed  CAS  Google Scholar 

  33. Fogari R, Zoppi A, Derosa G, et al. Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. J Hum Hypertens 2007; 21 (3): 220–4.

    PubMed  CAS  Google Scholar 

  34. Ogihara T, Saruta T, Rakugi H, et al., COLM study investigators. Rationale, study design and implementation of the COLM study: the combination of OLMesartan and calcium channel blocker or diuretic in high-risk elderly hypertensive patients. Hypertens Res 2009; 32 (2): 163–7.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the Ministry of Sciences and Technology of the People’s Republic of China (Grant No. 2006BAI01A03). We would like to express our gratitude to the doctors participating in the CHIEF study and thank Dawnrays Pharmaceutical (Holdings) Limited Company for providing the study drugs for free. —Liyuan Ma and Yong Zhao are co-first authors, and contributed equally to this work. —Conflicts of interest: The authors have no conflicts of interest directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Evidence-Based Medicine, Cardiovascular Institute and Fuwai Hospital, 167 Beilishi Road, Beijing, 100037, China

    Liyuan Ma,  Wen Wang, Yuqing Zhang, Qing Deng, Mingbo Liu & Lisheng Liu

  2. Department of Geriatric Cardiology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China

    Yong Zhao & Jianchun Wang

  3. Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong Province, China

    Hui Sun

  4. Clinical Trial and Research Center, Beijing Hypertension League Institute, Chinese Hypertension League, Beijing, China

    Lisheng Liu

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  1. Liyuan Ma
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  2. Wen Wang
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  3. Yong Zhao
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  4. Yuqing Zhang
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  5. Qing Deng
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  8. Jianchun Wang
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  9. Lisheng Liu
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Correspondence to Wen Wang.

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Ma, L., Wang, W., Zhao, Y. et al. Combination of Amlodipine plus Angiotensin Receptor Blocker or Diuretics in High-Risk Hypertensive Patients. Am J Cardiovasc Drugs 12, 137–142 (2012). https://doi.org/10.2165/11598110-000000000-00000

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