Comparison Therapies in the Treatment of Hypertension. The ASCOT and ACCOMPLISH Trial

  • Nikolaos Magkas
  • Athanasia Kapota
  • Costas Tsioufis


Combination therapy in hypertension, defined as the use of more than one antihypertensive agents in a hypertensive individual, is an issue of increasing interest, as in the majority of patients monotherapy does not achieve blood pressure control. Combination therapy seems safe, effective and convenient and several regimens are available in single-pill form, thereby facilitating compliance. Selection of the proper regimen remains a matter of debate, since data are in many cases conflicting and recommendations of guidelines of different hypertension societies are not always uniform. Although in many hypertension trials a large proportion of participants received more than one antihypertensive drugs, most of the available evidence is indirect, because few studies intended by design to compare two or more different combinations. ASCOT and ACCOMPLISH are considered the landmark trials in the comparison of combination therapies and had a great impact on hypertension guidelines and everyday clinical practice.


Combination treatment Single-pill form Efficacy ASCOT trial ACCOMPLISH trial 



Ambulatory blood pressure monitoring


American College of Cardiology


Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension


Angiotensin-converting enzyme inhibitor


Atrial fibrillation


American Heart Association


Augmentation index


Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial


Angiotensin receptor blocker


Anglo-Scandinavian Cardiac Outcomes Trial


Anglo-Scandinavian Cardiac Outcomes Trial- Blood Pressure Lowering Arm


Anglo-Scandinavian Cardiac Outcomes Trial- Lipid Lowering Arm


American Society of Hypertension




British Hypertension Society


Body mass index


Brain natriuretic peptide


Blood pressure


Conduit Artery Function Evaluation


Calcium channel blockers


Coronary heart disease


Confidence interval


Chronic kidney disease




Cardiovascular disease


Estimated glomerular filtration rate


European Society of Cardiology


European Society of Hypertension


End-stage renal disease


High-density lipoprotein


Heart failure


Heart failure with reduced ejection fraction


Heart Outcomes Prevention Evaluation


Hazard ratio




International Society of Hypertension


Joint National Committee


Losartan Intervention for Endpoint reduction in hypertension


Left ventricle/left ventricular


Left ventricular hypertrophy


Myocardial infarction


Mineralocorticoid receptor antagonist


National Institute for Health and Clinical Excellence


ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial


Peripheral artery disease


Pulse wave velocity


Renin-angiotensin-aldosterone system


Randomized controlled trial


Standard deviation


Systolic Hypertension in the Elderly Program


ST-segment elevation myocardial infarction


Valsartan Antihypertensive Long-term Use Evaluation


  1. 1.
    Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, et al. 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). J Hypertens. 2013;31(7):1281–357. Scholar
  2. 2.
    Byrd JB, Zeng C, Tavel HM, Magid DJ, O’Connor PJ, Margolis KL, et al. Combination therapy as initial treatment for newly diagnosed hypertension. Am Heart J. 2011;162(2):340–6. Epub 2011 Jul 18.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Corrao G, Nicotra F, Parodi A, Zambon A, Heiman F, Merlino L, et al. Cardiovascular protection by initial and subsequent combination of antihypertensive drugs in daily life practice. Hypertension. 2011;58(4):566–72. Scholar
  4. 4.
    Gradman AH, Basile JN, Carter BL, Bakris GL. American Society of Hypertension Writing Group. Combination therapy in hypertension. J Clin Hypertens (Greenwich). 2011;13(3):146–54. Scholar
  5. 5.
    Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, 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.CrossRefGoogle Scholar
  6. 6.
    Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009;122(3):290–300.CrossRefGoogle Scholar
  7. 7.
    Corrao G, Parodi A, Zambon A, Heiman F, Filippi A, Cricelli C, et al. Reduced discontinuation of antihypertensive treatment by two-drug combination as first step. Evidence from daily life practice. J Hypertens. 2010;28(7):1584–90.CrossRefGoogle Scholar
  8. 8.
    Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–310.CrossRefGoogle Scholar
  9. 9.
    Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension. 2010;55(2):399–407. Epub 2009 Dec 21.CrossRefPubMedGoogle Scholar
  10. 10.
    Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547–53. Scholar
  11. 11.
    Kalra S, Kalra B, Agrawal N. Combination therapy in hypertension: an update. Diabetol Metab Syndr. 2010;2(1):44. Scholar
  12. 12.
    Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007;369(9557):201–7.CrossRefGoogle Scholar
  13. 13.
    Mancia G, Grassi G, Zanchetti A. New-onset diabetes and antihypertensive drugs. J Hypertens. 2006;24(1):3–10.CrossRefGoogle Scholar
  14. 14.
    Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, 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;366(9489):895–906.CrossRefGoogle Scholar
  15. 15.
    Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417–28. Scholar
  16. 16.
    Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators. J Hypertens. 2001;19(6):1139–47.CrossRefGoogle Scholar
  17. 17.
    Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149–58.CrossRefGoogle Scholar
  18. 18.
    Ostergren J, Poulter NR, Sever PS, Dahlöf B, Wedel H, Beevers G, et al. The Anglo-Scandinavian Cardiac Outcomes Trial: blood pressure-lowering limb: effects in patients with type II diabetes. J Hypertens. 2008;26(11):2103–11. Scholar
  19. 19.
    Pahor M, Psaty BM, Alderman MH, Applegate WB, Williamson JD, Cavazzini C, et al. Health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: a meta-analysis of randomised controlled trials. Lancet. 2000;356(9246):1949–54.CrossRefGoogle Scholar
  20. 20.
    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.CrossRefGoogle Scholar
  21. 21.
    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289(19):2560–72.CrossRefGoogle Scholar
  22. 22.
    Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995–1003.CrossRefGoogle Scholar
  23. 23.
    Lindholm LH, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005;366(9496):1545–53.CrossRefGoogle Scholar
  24. 24.
    Bradley HA, Wiysonge CS, Volmink JA, Mayosi BM, Opie LH. How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis. J Hypertens. 2006;24(11):2131–41.CrossRefGoogle Scholar
  25. 25.
    Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet. 2004;364(9446):1684–9.CrossRefGoogle Scholar
  26. 26.
    Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH. Beta-blockers for hypertension. Cochrane Database Syst Rev. 2017;1:CD002003. Scholar
  27. 27.
    Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA. 2003;290(21):2805–16.CrossRefGoogle Scholar
  28. 28.
    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. Scholar
  29. 29.
    Poulter NR, Wedel H, Dahlöf B, Sever PS, Beevers DG, Caulfield M, et al. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet. 2005;366(9489):907–13.CrossRefGoogle Scholar
  30. 30.
    Turnbull F, Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362(9395):1527–35.CrossRefGoogle Scholar
  31. 31.
    Ritter J, Warren J. ASCOT–old or new drugs for blood pressure? Br J Clin Pharmacol. 2006;61(3):363.CrossRefGoogle Scholar
  32. 32.
    Burrill PD. ASCOT: a tale of two treatment regimens: is ASCOT-BPLA being hyped-up? BMJ. 2005;331(7523):1022.CrossRefGoogle Scholar
  33. 33.
    Weber MA, Julius S, Kjeldsen SE, Brunner HR, Ekman S, Hansson L, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet. 2004;363(9426):2049–51.CrossRefGoogle Scholar
  34. 34.
    Hastie CE, Jeemon P, Coleman H, McCallum L, Patel R, Dawson J, et al. Long-term and ultra long-term blood pressure variability during follow-up and mortality in 14,522 patients with hypertension. Hypertension. 2013;62(4):698–705. Scholar
  35. 35.
    Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlöf B, et al. Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Lancet Neurol. 2010;9(5):469–80. Scholar
  36. 36.
    Gupta AK, Nasothimiou EG, Chang CL, Sever PS, Dahlöf B, Poulter NR, et al. Baseline predictors of resistant hypertension in the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT): a risk score to identify those at high-risk. J Hypertens. 2011;29(10):2004–13. Scholar
  37. 37.
    Gupta AK, Dahlof B, Dobson J, Sever PS, Wedel H, Poulter NR, Anglo-Scandinavian Cardiac Outcomes Trial Investigators. Determinants of new-onset diabetes among 19,257 hypertensive patients randomized in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm and the relative influence of antihypertensive medication. Diabetes Care. 2008;31(5):982–8. Scholar
  38. 38.
    Grimm C, Köberlein J, Wiosna W, Kresimon J, Kiencke P, Rychlik R. New-onset diabetes and antihypertensive treatment. GMS Health Technol Assess. 2010;6:Doc03. Scholar
  39. 39.
    Sharma AM, Pischon T, Hardt S, Kunz I, Luft FC. Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension. 2001;37(2):250–4.CrossRefGoogle Scholar
  40. 40.
    Fonseca VA. Effects of beta-blockers on glucose and lipid metabolism. Curr Med Res Opin. 2010;26(3):615–29. Scholar
  41. 41.
    Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database Syst Rev. 2014;(5):CD003824.
  42. 42.
    Ladage D, Schwinger RH, Brixius K. Cardio-selective beta-blocker: pharmacological evidence and their influence on exercise capacity. Cardiovasc Ther. 2013;31(2):76–83. Scholar
  43. 43.
    Zillich AJ, Garg J, Basu S, Bakris GL, Carter BL. Thiazide diuretics, potassium, and the development of diabetes: a quantitative review. Hypertension. 2006;48(2):219–24.CrossRefGoogle Scholar
  44. 44.
    Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315–81. Scholar
  45. 45.
    James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20. Scholar
  46. 46.
    Bakris GL, Sarafidis PA, Weir MR, Dahlöf B, Pitt B, Jamerson K, et al. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010;375(9721):1173–81. Scholar
  47. 47.
    Sever P, Dahlöf B, Poulter N, Wedel H, Beevers G, Caulfield M, et al. Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial. Eur Heart J. 2006;27(24):2982–8.CrossRefGoogle Scholar
  48. 48.
    Athyros VG, Mikhailidis DP, Papageorgiou AA, Bouloukos VI, Pehlivanidis AN, Symeonidis AN, et al. Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease. J Hum Hypertens. 2004;18(11):781–8.CrossRefGoogle Scholar
  49. 49.
    Veronesi M, Cicero AF, Prandin MG, Dormi A, Cosentino E, Strocchi E, et al. A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice. Vasc Health Risk Manag. 2007;3(6):999–1005.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Bangalore S, Fakheri R, Toklu B, Ogedegbe G, Weintraub H, Messerli FH. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients without heart failure? Insights from 254,301 patients from randomized trials. Mayo Clin Proc. 2016;91(1):51–60. Scholar
  51. 51.
    ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59. Scholar
  52. 52.
    Cowan BR, Young AA. Left ventricular hypertrophy and renin-angiotensin system blockade. Curr Hypertens Rep. 2009;11(3):167–72.CrossRefGoogle Scholar
  53. 53.
    Montecucco F, Pende A, Mach F. The renin-angiotensin system modulates inflammatory processes in atherosclerosis: evidence from basic research and clinical studies. Mediat Inflamm. 2009;2009:752406. Scholar
  54. 54.
    Jamerson KA, Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension Trial. The first hypertension trial comparing the effects of two fixed-dose combination therapy regimens on cardiovascular events: Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH). J Clin Hypertens (Greenwich). 2003;5(4 Suppl 3):29–35.CrossRefGoogle Scholar
  55. 55.
    Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145–53.CrossRefGoogle Scholar
  56. 56.
    Mason RP. Mechanisms of plaque stabilization for the dihydropyridine calcium channel blocker amlodipine: review of the evidence. Atherosclerosis. 2002;165(2):191–9.CrossRefGoogle Scholar
  57. 57.
    Mason RP. Atheroprotective effects of long-acting dihydropyridine-type calcium channel blockers: evidence from clinical trials and basic scientific research. Cerebrovasc Dis. 2003;16(Suppl 3):11–7.CrossRefGoogle Scholar
  58. 58.
    Cohen DL, Townsend RR. Will the results of the ACCOMPLISH trial affect the recommendations of JNC 8? J Clin Hypertens (Greenwich). 2009;11(2):100–1. Scholar
  59. 59.
    Ferrari R. Angiotensin converting enzyme inhibitor-calcium antagonist combination: an alliance for cardioprotection? J Hypertens Suppl. 1997;15(2):S109–17.CrossRefGoogle Scholar
  60. 60.
    Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113(9):1213–25.CrossRefGoogle Scholar
  61. 61.
    Dudenbostel T, Glasser SP. Effects of antihypertensive drugs on arterial stiffness. Cardiol Rev. 2012;20(5):259–63. Scholar
  62. 62.
    Protogerou AD, Stergiou GS, Vlachopoulos C, Blacher J, Achimastos A. The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part II: evidence for specific class-effects of antihypertensive drugs on pressure amplification. Curr Pharm Des. 2009;15(3):272–89.CrossRefGoogle Scholar
  63. 63.
    Boutouyrie P, Achouba A, Trunet P, Laurent S, EXPLOR Trialist Group. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR study. Hypertension. 2010;55(6):1314–22. Scholar
  64. 64.
    Jiang XJ, O’Rourke MF, Zhang YQ, He XY, Liu LS. Superior effect of an angiotensin-converting enzyme inhibitor over a diuretic for reducing aortic systolic pressure. J Hypertens. 2007;25(5):1095–9.CrossRefGoogle Scholar
  65. 65.
    Manisty CH, Hughes AD. Meta-analysis of the comparative effects of different classes of antihypertensive agents on brachial and central systolic blood pressure, and augmentation index. Br J Clin Pharmacol. 2013;75(1):79–92. Scholar
  66. 66.
    Vlachopoulos C, Aznaouridis K, O’Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J. 2010;31(15):1865–71. Scholar
  67. 67.
    Safar ME, Blacher J, Pannier B, Guerin AP, Marchais SJ, Guyonvarc’h PM, et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39(3):735–8.CrossRefGoogle Scholar
  68. 68.
    Tapp RJ, Sharp A, Stanton AV, O’Brien E, Chaturvedi N, Poulter NR, et al. Differential effects of antihypertensive treatment on left ventricular diastolic function: an ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) substudy. J Am Coll Cardiol. 2010;55(17):1875–81. Scholar
  69. 69.
    Barron AJ, Hughes AD, Sharp A, Baksi AJ, Surendran P, Jabbour RJ, et al. Long-term antihypertensive treatment fails to improve E/e’ despite regression of left ventricular mass: an Anglo-Scandinavian cardiac outcomes trial substudy. Hypertension. 2014;63(2):252–8. Scholar
  70. 70.
    Dolan E, Stanton AV, Thom S, Caulfield M, Atkins N, McInnes G, et al. Ambulatory blood pressure monitoring predicts cardiovascular events in treated hypertensive patients–an Anglo-Scandinavian cardiac outcomes trial substudy. J Hypertens. 2009;27(4):876–85. Scholar
  71. 71.
    Hansen TW, Li Y, Boggia J, Thijs L, Richart T, Staessen JA. Predictive role of the nighttime blood pressure. Hypertension. 2011;57(1):3–10. Scholar
  72. 72.
    Thom S, Stettler C, Stanton A, Witt N, Tapp R, Chaturvedi N, et al. Differential effects of antihypertensive treatment on the retinal microcirculation: an Anglo-Scandinavian Cardiac Outcomes Trial substudy. Hypertension. 2009;54(2):405–8. Scholar
  73. 73.
    Chapman N, Chang CL, Dahlöf B, Sever PS, Wedel H, Poulter NR, et al. Effect of doxazosin gastrointestinal therapeutic system as third-line antihypertensive therapy on blood pressure and lipids in the Anglo-Scandinavian Cardiac Outcomes Trial. Circulation. 2008;118(1):42–8. Scholar
  74. 74.
    The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). JAMA. 2000;283(15):1967–75.CrossRefGoogle Scholar
  75. 75.
    Chapman N, Dobson J, Wilson S, Dahlöf B, Sever PS, Wedel H, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49(4):839–45.CrossRefGoogle Scholar
  76. 76.
    Gupta AK, Poulter NR, Dobson J, Eldridge S, Cappuccio FP, Caulfield M, et al. Ethnic differences in blood pressure response to first and second-line antihypertensive therapies in patients randomized in the ASCOT Trial. Am J Hypertens. 2010;23(9):1023–30. Scholar
  77. 77.
    Wright JT Jr, Dunn JK, Cutler JA, Davis BR, Cushman WC, Ford CE, et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005;293(13):1595–608.CrossRefGoogle Scholar
  78. 78.
    Flack JM, Sica DA, Bakris G, Brown AL, Ferdinand KC, Grimm RH Jr, et al. Management of high blood pressure in Blacks: an update of the International Society on Hypertension in Blacks consensus statement. Hypertension. 2010;56(5):780–800. Scholar
  79. 79.
    Byrd JB, Bakris G, Jamerson K. The contribution of the ACCOMPLISH trial to the treatment of stage 2 hypertension. Curr Hypertens Rep. 2014;16(3):419. Scholar
  80. 80.
    McAlister FA, Herman RJ, Khan NA, Rabkin SW, Campbell N, Canadian Hypertension Education Program. Putting ACCOMPLISH into context: management of hypertension in 2010. CMAJ. 2010;182(15):1600–1. Scholar
  81. 81.
    Jamerson KA, Devereux R, Bakris GL, Dahlöf B, Pitt B, Velazquez EJ, et al. Efficacy and duration of benazepril plus amlodipine or hydrochlorothiazide on 24-hour ambulatory systolic blood pressure control. Hypertension. 2011;57(2):174–9. Scholar
  82. 82.
    SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265(24):3255–64.CrossRefGoogle Scholar
  83. 83.
    Ernst ME, Carter BL, Basile JN. All thiazide-like diuretics are not chlorthalidone: putting the ACCOMPLISH study into perspective. J Clin Hypertens (Greenwich). 2009;11(1):5–10. Scholar
  84. 84.
    Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, et al. Guidelines on the management of stable angina pectoris: executive summary: the Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J. 2006;27(11):1341–81.CrossRefGoogle Scholar
  85. 85.
    Zhou MS, Schulman IH, Jaimes EA, Raij L. Thiazide diuretics, endothelial function, and vascular oxidative stress. J Hypertens. 2008;26(3):494–500. Scholar
  86. 86.
    Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB. Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program. Hypertension. 2000;35(5):1025–30.CrossRefGoogle Scholar
  87. 87.
    Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens. 2009;27(11):2121–58. Scholar
  88. 88.
    Giles TD, Houston MC. Do diuretics diminish the predicted benefits on ischemic heart disease events of lowering blood pressure in hypertension? Messages from ALLHAT, ACCOMPLISH, and ACCORD. J Clin Hypertens (Greenwich). 2010;12(7):469–71. Scholar
  89. 89.
    Matsui Y, Eguchi K, O’Rourke MF, Ishikawa J, Miyashita H, Shimada K, et al. Differential effects between a calcium channel blocker and a diuretic when used in combination with angiotensin II receptor blocker on central aortic pressure in hypertensive patients. Hypertension. 2009;54(4):716–23. Scholar
  90. 90.
    Ghiadoni L, Bruno RM, Cartoni G, Stea F, Magagna A, Virdis A, et al. Combination therapy with lercanidipine and enalapril reduced central blood pressure augmentation in hypertensive patients with metabolic syndrome. Vasc Pharmacol. 2017;92:16–21. Scholar
  91. 91.
    De Ciuceis C, Salvetti M, Rossini C, Muiesan ML, Paini A, Duse S, et al. Effect of antihypertensive treatment on microvascular structure, central blood pressure and oxidative stress in patients with mild essential hypertension. J Hypertens. 2014;32(3):565–74. Scholar
  92. 92.
    Matsui Y, O’Rourke MF, Hoshide S, Ishikawa J, Shimada K, Kario K. Combined effect of angiotensin II receptor blocker and either a calcium channel blocker or diuretic on day-by-day variability of home blood pressure: the Japan Combined Treatment With Olmesartan and a Calcium-Channel Blocker Versus Olmesartan and Diuretics Randomized Efficacy Study. Hypertension. 2012;59(6):1132–8. Scholar
  93. 93.
    Webb AJ, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet. 2010;375(9718):906–15. Scholar
  94. 94.
    Zhang Y, Agnoletti D, Safar ME, Blacher J. Effect of antihypertensive agents on blood pressure variability: the Natrilix SR versus candesartan and amlodipine in the reduction of systolic blood pressure in hypertensive patients (X-CELLENT) study. Hypertension. 2011;58(2):155–60. Scholar
  95. 95.
    Weber MA, Jamerson K, Bakris GL, Weir MR, Zappe D, Zhang Y, et al. Effects of body size and hypertension treatments on cardiovascular event rates: subanalysis of the ACCOMPLISH randomised controlled trial. Lancet. 2013;381(9866):537–45. Scholar
  96. 96.
    Wassertheil-Smoller S, Fann C, Allman RM, Black HR, Camel GH, Davis B, et al. Relation of low body mass to death and stroke in the systolic hypertension in the elderly program. The SHEP Cooperative Research Group. Arch Intern Med. 2000;160(4):494–500.CrossRefGoogle Scholar
  97. 97.
    Task Force Members, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. 2013 ESC Guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949–3003. Scholar
  98. 98.
    Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022–31.CrossRefGoogle Scholar
  99. 99.
    Rimoldi SF, Messerli FH, Chavez P, Stefanini GG, Scherrer U. Efficacy and safety of calcium channel blocker/diuretics combination therapy in hypertensive patients: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17(3):193–9. Scholar
  100. 100.
    Jadhav U, Hiremath J, Namjoshi DJ, Gujral VK, Tripathi KK, Siraj M, et al. Blood pressure control with a single-pill combination of indapamide sustained-release and amlodipine in patients with hypertension: the EFFICIENT study. PLoS One. 2014;9(4):e92955. eCollection 2014.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Authors/Task Force Members, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541–619. Scholar
  102. 102.
    Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2017;39:119–77. Scholar
  103. 103.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) . Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129–200. Scholar
  104. 104.
    Sever PS, Poulter NR, Elliott WJ, Jonsson MC, Black HR. Blood pressure reduction is not the only determinant of outcome. Circulation. 2006;113(23):2754–72. discussion 2773-4CrossRefGoogle Scholar
  105. 105.
    Weder AB. The Avoiding Cardiovascular events through COMbination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial: a comparison of first-line combination therapies. Expert Opin Pharmacother. 2005;6(2):275–81.CrossRefGoogle Scholar
  106. 106.
    Leung AA, Daskalopoulou SS, Dasgupta K, McBrien K, Butalia S, Zarnke KB, et al. Hypertension Canada’s 2017 Guidelines for diagnosis, risk assessment, prevention, and treatment of hypertension in adults. Can J Cardiol. 2017;33(5):557–76. Scholar
  107. 107.
    Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16(1):14–26. Scholar
  108. 108.
    National Institute for Health and Care Excellence (NICE) Clinical Guidelines. Hypertension: clinical management of primary hypertension in adults. NICE Clinical Guideline 127. 2011.
  109. 109.
    Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2017. pii: HYP.0000000000000066; Scholar
  110. 110.
    van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad JJ, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158,998 patients. Eur Heart J. 2012;33(16):2088–97. Epub 2012 Apr 17.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Costanzo P, Perrone-Filardi P, Petretta M, Marciano C, Vassallo E, Gargiulo P, et al. Calcium channel blockers and cardiovascular outcomes: a meta-analysis of 175,634 patients. J Hypertens. 2009;27(6):1136–51. Scholar
  112. 112.
    Turnbull F, Neal B, Algert C, Chalmers J, Chapman N, Cutler J, et al. Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials. Arch Intern Med. 2005;165(12):1410–9.CrossRefGoogle Scholar
  113. 113.
    Xue H, Lu Z, Tang WL, Pang LW, Wang GM, Wong GW, et al. First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. Cochrane Database Syst Rev. 2015;1:CD008170. Scholar
  114. 114.
    National Institute for Health and Clinical Excellence. Hypertension: management of hypertension in adults in primary care. (Clinical guideline 34). 2006.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Nikolaos Magkas
    • 1
  • Athanasia Kapota
    • 2
  • Costas Tsioufis
    • 3
    • 4
  1. 1.First Cardiology Clinic, Medical School, National and Kapodistrian University of Athens, Hippokration HospitalAthensGreece
  2. 2.Hipporcration General Hospital of AthensAthensGreece
  3. 3.First Cardiology Clinic, University of Athens, Hippokration HospitalAthensGreece
  4. 4.Georgetown UniversityWashington, DCUSA

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