The four major classes of antihypertensive drugs—diuretics, β-blockers, calcium channel blockers, and renin-angiotensin system inhibitors (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers)—have significant qualitative and quantitative differences in the adverse effects they cause. Structural and chemical differences have been identified within these classes, especially among the calcium channel blockers and, to a lesser extent, among the thiazide/thiazide-like diuretics. However, it has been more difficult to demonstrate that these differences translate into differential effects with respect to either the surrogate endpoint of blood pressure reduction or, more importantly, hypertension-related cardiovascular complications. Based on a hierarchy-of-evidence approach, differences are apparent between hydrochlorothiazide and chlorthalidone based on evidence of moderate quality. Low-quality evidence suggests atenolol is less effective than other β-blockers. However, no significant intraclass differences have been established among the other classes of antihypertensive drugs.


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Literature Cited

  1. Lawes CMM, Vander Hoorn S, Rodgers A. 1.  2008. Global burden of blood-pressure-related disease, 2001. Lancet 371:1513–18 [Google Scholar]
  2. Lawes CMM, Vander Hoorn S, Law MR, Elliott P, MacMahon S, Rodgers A. 2.  2006. Blood pressure and the global burden of disease 2000. Part II: estimates of attributable burden. J. Hypertens. 24:423–30 [Google Scholar]
  3. Wang JG, Staessen JA, Franklin SS, Fagard R, Gueyffier F. 3.  2005. Systolic and diastolic blood pressure lowering as determinants of cardiovascular outcome. Hypertension 45:907–13 [Google Scholar]
  4. Turnbull F, Neal B, Ninomiya T, Algert C, Arima H. 4.  et al. 2008. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 336:1121 [Google Scholar]
  5. Law MR, Morris JK, Wald NJ. 5.  2009. 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 338:b1665 [Google Scholar]
  6. Fretheim A, Odgaard-Jensen J, Brørs O, Madsen S, Njølstad I. 6.  et al. 2012. Comparative effectiveness of antihypertensive medication for primary prevention of cardiovascular disease: systematic review and multiple treatments meta-analysis. BMC Med. 10:33 [Google Scholar]
  7. McAlister FA, Laupacis A, Wells GA, Sackett DL. 7.  1999. Users' guides to the medical literature: XIX. Applying clinical trial results: B. Guidelines for determining whether a drug is exerting (more than) a class effect. JAMA 282:1371–77 [Google Scholar]
  8. McAlister FA, Sackett DL. 8.  2001. Active-control equivalence trials and antihypertensive agents. Am. J. Med. 111:553–58 [Google Scholar]
  9. Greene WL, Concato J, Feinstein AR. 9.  2000. Claims of equivalence in medical research: Are they supported by the evidence?. Ann. Intern. Med. 132:715–22 [Google Scholar]
  10. Bucher HC, Guyatt GH, Griffith LE, Walter SD. 10.  1997. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J. Clin. Epidemiol. 50:683–91 [Google Scholar]
  11. Jansen JP, Fleurence R, Devine B, Itzler R, Barrett A. 11.  et al. 2011. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on Indirect Treatment Comparisons Good Research Practices: part 1. Value Health 14:417–28 [Google Scholar]
  12. Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH. 12.  et al. 1990. Blood pressure, stroke, and coronary heart disease: part 2, short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 335:827–38 [Google Scholar]
  13. McAlister FA. 13.  2002. Commentary: Relative treatment effects are consistent across the spectrum of underlying risks… usually. Int. J. Epidemiol. 31:76–77 [Google Scholar]
  14. Song F, Altman DG, Glenny AM, Deeks JJ. 14.  2003. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 326:472 [Google Scholar]
  15. Floyd JS, Psaty BM. 15.  2012. Observational comparative effectiveness studies of drug therapies: high-quality answers or important clinical questions?. Arch. Intern. Med. 172:1412–14 [Google Scholar]
  16. Shrank WH, Patrick AR, Brookhart MA. 16.  2011. Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J. Gen. Intern. Med. 26:546–50 [Google Scholar]
  17. Beyer KH, Baer JE. 17.  1961. Physiological basis for the action of newer diuretic agents. Pharmacol. Rev. 13:517–62 [Google Scholar]
  18. Tamargo J, Segura J, Ruilope LM. 18.  2014. Diuretics in the treatment of hypertension. Part 1: thiazide and thiazide-like diuretics. Expert Opin. Pharmacother. 15:527–47 [Google Scholar]
  19. Mroczek WJ. 19.  1983. Indapamide: clinical pharmacology, therapeutic efficacy in hypertension, and adverse effects. Pharmacotherapy 3:61–67 [Google Scholar]
  20. Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JJG, Phillips BB. 20.  et al. 2006. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension 47:352–58 [Google Scholar]
  21. Ernst ME, Carter BL, Zheng S, Grimm RH Jr. 21.  2010. Meta-analysis of dose-response characteristics of hydrochlorothiazide and chlorthalidone: effects on systolic blood pressure and potassium. Am. J. Hypertens. 23:440–46 [Google Scholar]
  22. Peterzan MA, Hardy R, Chaturvedi N, Hughes AD. 22.  2012. Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate. Hypertension 59:1104–9 [Google Scholar]
  23. Roush GC, Holford TR, Guddati AK. 23.  2012. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension 59:1110–17 [Google Scholar]
  24. Dhalla IA, Gomes T, Yao Z, Nagge J, Persaud N. 24.  et al. 2013. Chlorthalidone versus hydrochlorothiazide for the treatment of hypertension in older adults: a population-based cohort study. Ann. Intern. Med. 158:447–55 [Google Scholar]
  25. Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB. 25.  2011. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension 57:689–94 [Google Scholar]
  26. Maione A, Navaneethan SD, Graziano G, Mitchell R, Johnson D. 26.  et al. 2011. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro- and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials. Nephrol. Dial. Transplant. 26:2827–47 [Google Scholar]
  27. Al-Mallah MH, Tleyjeh IM, Abdel-Latif AA, Weaver WD. 27.  2006. Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function: a systematic review and meta-analysis of randomized controlled trials. J. Am. Coll. Cardiol. 47:1576–83 [Google Scholar]
  28. Flather MD, Yusuf S, Køber L, Pfeffer M, Hall A. 28.  et al. 2000. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. Lancet 355:1575–81 [Google Scholar]
  29. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. 29.  2000. Effects of an angiotensin-converting–enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N. Engl. J. Med. 342:145–53 [Google Scholar]
  30. Verdecchia P, Angeli F, Cavallini C, Gattobigio R, Gentile G. 30.  et al. 2009. Blood pressure reduction and renin-angiotensin system inhibition for prevention of congestive heart failure: a meta-analysis. Eur. Heart J. 30:679–88 [Google Scholar]
  31. Unger T. 31.  2002. The role of the renin-angiotensin system in the development of cardiovascular disease. Am. J. Cardiol. 89:3A–9A [Google Scholar]
  32. Zaman MA, Oparil S, Calhoun DA. 32.  2002. Drugs targeting the renin-angiotensin-aldosterone system. Nat. Rev. Drug Discov. 1:621–36 [Google Scholar]
  33. Dzau VJ, Bernstein K, Celermajer D, Cohen J, Dahlöf B. 33.  et al. 2002. Pathophysiologic and therapeutic importance of tissue ACE: a consensus report. Cardiovasc. Drugs Ther. 16:149–60 [Google Scholar]
  34. Michel MC, Foster C, Brunner HR, Liu L. 34.  2013. A systematic comparison of the properties of clinically used angiotensin II type 1 receptor antagonists. Pharmacol. Rev. 65:809–48 [Google Scholar]
  35. Fyhrquist F. 35.  1986. Clinical pharmacology of the ACE inhibitors. Drugs 32:Suppl. 533–39 [Google Scholar]
  36. Brown NJ, Vaughan DE. 36.  1998. Angiotensin-converting enzyme inhibitors. Circulation 97:1411–20 [Google Scholar]
  37. Heel RC, Brogden RN, Speight TM, Avery GS. 37.  1980. Captopril: a preliminary review of its pharmacological properties and therapeutic efficacy. Drugs 20:409–52 [Google Scholar]
  38. White CM. 38.  1998. Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors. Pharmacotherapy 18:588–99 [Google Scholar]
  39. Ahuja K, Charap MH. 39.  2010. Management of perioperative hypertensive urgencies with parenteral medications. J. Hosp. Med. 5:E11–16 [Google Scholar]
  40. Flack JM, Nasser SA. 40.  2011. Benefits of once-daily therapies in the treatment of hypertension. Vasc. Health Risk Manag. 7:777–87 [Google Scholar]
  41. Furberg CD, Psaty BM. 41.  2003. Should evidence-based proof of drug efficacy be extrapolated to a “class of agents”?. Circulation 108:2608–10 [Google Scholar]
  42. Shah AD, Arora RR. 42.  2005. Tissue angiotensin-converting enzyme inhibitors: Are they more effective than serum angiotensin-converting enzyme inhibitors?. Clin. Cardiol. 28:551–55 [Google Scholar]
  43. Hilleman DE, Lucas BD Jr. 43.  2004. Angiotensin-converting enzyme inhibitors and stroke risk: benefit beyond blood pressure reduction?. Pharmacotherapy 24:1064–76 [Google Scholar]
  44. Sica DA. 44.  2001. The Heart Outcomes Prevention Evaluation study: angiotensin-converting enzyme inhibitors: Are their benefits a class effect or do individual agents differ?. Curr. Opin. Nephrol. Hypertens. 10:597–601 [Google Scholar]
  45. Svensson P, de Faire U, Sleight P, Yusuf S, Östergren J. 45.  2001. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE substudy. Hypertension 38:E28–32 [Google Scholar]
  46. Staessen JA, Wang JG, Thijs L. 46.  2001. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet 358:1305–15 [Google Scholar]
  47. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I. 47.  et al. 2008. Telmisartan, ramipril, or both in patients at high risk for vascular events. N. Engl. J. Med. 358:1547–59 [Google Scholar]
  48. McAlister FA. 48.  2012. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are beneficial in normotensive atherosclerotic patients: a collaborative meta-analysis of randomized trials. Eur. Heart J. 33:505–14 [Google Scholar]
  49. Turnbull F, Neal B, Pfeffer M, Kostis J, Algert C. 49.  et al. 2007. Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system. J. Hypertens. 25:951–58 [Google Scholar]
  50. Siegl PK. 50.  1993. Discovery of losartan, the first specific non-peptide angiotensin II receptor antagonist. J. Hypertens. Suppl. 11:S19–22 [Google Scholar]
  51. Kassler-Taub K, Littlejohn T, Elliott W, Ruddy T, Adler E. 51.  1998. Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan, in mild-to-moderate hypertension. Am. J. Hypertens. 11:445–53 [Google Scholar]
  52. Takagi H, Niwa M, Mizuno Y, Goto SN, Umemoto T. 52.  2013. A meta-analysis of randomized trials of telmisartan versus losartan for reduction of ambulatory blood pressure. Hypertens. Res. 36:959–66 [Google Scholar]
  53. Hamada T, Ichida K, Hosoyamada M, Mizuta E, Yanagihara K. 53.  et al. 2008. Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients. Am. J. Hypertens. 21:1157–62 [Google Scholar]
  54. Choi HK, Soriano LC, Zhang Y, Rodríguez LAG. 54.  2012. Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ 344:d8190 [Google Scholar]
  55. Soltani Z, Rasheed K, Kapusta DR, Reisin E. 55.  2013. Potential role of uric acid in metabolic syndrome, hypertension, kidney injury, and cardiovascular diseases: Is it time for reappraisal?. Curr. Hypertens. Rep. 15:175–81 [Google Scholar]
  56. Derosa G, Cicero AFG, D'angelo A, Ragonesi PD, Ciccarelli L. 56.  et al. 2006. Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-α. Hypertens. Res. 29:849–56 [Google Scholar]
  57. Murakami K, Wada J, Ogawa D, Horiguchi CS, Miyoshi T. 57.  et al. 2013. The effects of telmisartan treatment on the abdominal fat depot in patients with metabolic syndrome and essential hypertension: Abdominal fat Depot Intervention Program of Okayama (ADIPO). Diabetes Vasc. Dis. Res. 10:93–96 [Google Scholar]
  58. Suksomboon N, Poolsup N, Prasit T. 58.  2012. Systematic review of the effect of telmisartan on insulin sensitivity in hypertensive patients with insulin resistance or diabetes. J. Clin. Pharmacol. Ther. 37:319–27 [Google Scholar]
  59. Antoniou T, Camacho X, Yao Z, Gomes T, Juurlink DN, Mamdani MM. 59.  2013. Comparative effectiveness of angiotensin-receptor blockers for preventing macrovascular disease in patients with diabetes: a population-based cohort study. CMAJ 185:1035–41 [Google Scholar]
  60. Haller H, Ito S, Izzo JL Jr, Januszewicz A, Katayama S. 60.  et al. 2011. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N. Engl. J. Med. 364:907–17 [Google Scholar]
  61. Imai E, Chan JC, Ito S, Yamasaki T, Kobayashi F. 61.  et al. 2011. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia 54:2978–86 [Google Scholar]
  62. Padwal R, Lin M, Etminan M, Eurich DT. 62.  2014. Comparative effectiveness of olmesartan and other angiotensin receptor blockers in diabetes mellitus: retrospective cohort study. Hypertension 63:977–83 [Google Scholar]
  63. 63. US Food Drug Adm 2013. Olmesartan Medoxomil: drug safety communication—label changes to include intestinal problems (sprue-like enteropathy) Silver Spring, MD: US Food Drug Adm http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm359528.htm [Google Scholar]
  64. 64. US Food Drug Adm 2011. FDA drug safety communication: safety review update of Benicar (olmesartan) and cardiovascular events Silver Spring, MD: US Food Drug Adm. http://www.fda.gov/Drugs/DrugSafety/ucm251268.htm [Google Scholar]
  65. 65. MERIT-HF Study Group 1999. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353:2001–7 [Google Scholar]
  66. Freemantle N, Cleland J, Young P, Mason J, Harrison J. 66.  1999. β Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 318:1730 [Google Scholar]
  67. Borer JS, Comerford MB, Sowton E. 67.  1976. Assessment of metoprolol, a cardioselective beta-blocking agent, during chronic therapy in patients with angina pectoris. J. Int. Med. Res. 4:15–22 [Google Scholar]
  68. Khan N, McAlister FA. 68.  2006. Re-examining the efficacy of β-blockers for the treatment of hypertension: a meta-analysis. CMAJ 174:1737–42 [Google Scholar]
  69. Messerli FH, Grossman E, Goldbourt U. 69.  1998. Are β-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review. JAMA 279:1903–7 [Google Scholar]
  70. Kuyper LM, Khan NA. 70.  2014. Atenolol vs nonatenolol β-blockers for the treatment of hypertension: a meta-analysis. Can. J. Cardiol. 30:S47–53 [Google Scholar]
  71. Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A. 71.  et al. 2006. 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 113:1213–25 [Google Scholar]
  72. Schiffrin EL, Deng LY, Larochelle P. 72.  1994. Effects of a β-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension. Hypertension 23:83–91 [Google Scholar]
  73. Kirstein SL, Insel PA. 73.  2004. Autonomic nervous system pharmacogenomics: a progress report. Pharmacol. Rev. 56:31–52 [Google Scholar]
  74. Lund-Johansen P. 74.  1979. Hemodynamic consequences of long-term beta-blocker therapy: a 5-year follow-up study of atenolol. J. Cardiovasc. Pharmacol. 1:487–95 [Google Scholar]
  75. Teisman ACH, van Veldhuisen DJ, Boomsma F, de Kam PJ, Tjeerdsma G. 75.  et al. 2000. Chronic beta-blocker treatment in patients with advanced heart failure: effects on neurohormones. Int. J. Cardiol. 73:7–12 [Google Scholar]
  76. Minneman KP, Pittman RN, Molinoff PB. 76.  1981. β-Adrenergic receptor subtypes: properties, distribution, and regulation. Annu. Rev. Neurosci. 4:419–61 [Google Scholar]
  77. Berglund G, Andersson O. 77.  1981. Beta-blockers or diuretics in hypertension? A six year follow-up of blood pressure and metabolic side effects. Lancet 1:744–47 [Google Scholar]
  78. Bangalore S, Parkar S, Grossman E, Messerli FH. 78.  2007. A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus. Am. J. Cardiol. 100:1254–62 [Google Scholar]
  79. Poirier L, Lacourcière Y. 79.  2012. The evolving role of β-adrenergic receptor blockers in managing hypertension. Can. J. Cardiol. 28:334–40 [Google Scholar]
  80. Ekbom T, Dahlöf B, Hansson L, Lindholm LH, Scherstén B, Wester PO. 80.  1992. Antihypertensive efficacy and side effects of three beta-blockers and a diuretic in elderly hypertensives: a report from the STOP-Hypertension study. J. Hypertens. 10:1525–30 [Google Scholar]
  81. Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli FH. 81.  et al. 2004. Metabolic effects of carvedilol versus metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA 292:2227–36 [Google Scholar]
  82. Agabiti-Rosei E, Porteri E, Rizzoni D. 82.  2009. Arterial stiffness, hypertension, and rational use of nebivolol. Vasc. Health Risk Manag. 5:353–60 [Google Scholar]
  83. Mahmud A, Feely J. 83.  2008. β-Blockers reduce aortic stiffness in hypertension but nebivolol, not atenolol, reduces wave reflection. Am. J. Hypertens. 21:663–67 [Google Scholar]
  84. 84. Jt. Natl. Comm. Detect. Eval. Treat. High Blood Press 1993. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch. Intern. Med. 153154–83 [Google Scholar]
  85. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R. 85.  et al. 2007. 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). Eur. Heart J. 28:1462–536 [Google Scholar]
  86. Hackam DG, Quinn RR, Ravani P, Rabi DM, Dasgupta K. 86.  et al. 2013. The 2013 Canadian hypertension education program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can. J. Cardiol. 29:528–42 [Google Scholar]
  87. 87. Med. Res. Counc. Work. Party 1985. MRC trial of treatment of mild hypertension: principal results. BMJ 291:97–104 [Google Scholar]
  88. Dahlöf B, Lindholm LH, Hansson L, Scherstén B, Ekbom T, Wester PO. 88.  1991. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 338:1281–85 [Google Scholar]
  89. Wikstrand J, Warnold I, Tuomilehto J, Olsson G, Barber HJ. 89.  et al. 1991. Metoprolol versus thiazide diuretics in hypertension: morbidity results from the MAPHY study. Hypertension 17:579–88 [Google Scholar]
  90. Wilhelmsen L, Berglund G, Elmfeldt D, Fitzsimons T, Holzgreve H. 90.  et al. 1987. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. J. Hypertens. 5:561–72 [Google Scholar]
  91. 91. Med. Res. Counc. Work. Party 1992. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ 304:405–12 [Google Scholar]
  92. Bangalore S, Sawhney S, Messerli FH. 92.  2008. Relation of beta-blocker–induced heart rate lowering and cardioprotection in hypertension. J. Am. Coll. Cardiol. 52:1482–89 [Google Scholar]
  93. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G. 93.  et al. 2002. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359:995–1003 [Google Scholar]
  94. Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG. 94.  et al. 2005. 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 366:895–906 [Google Scholar]
  95. Lindholm LH, Carlberg B, Samuelsson O. 95.  2005. Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 366:1545–53 [Google Scholar]
  96. 96. Natl. Clin. Guidel. Cent 2011. Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34. London: Natl. Clin. Guidel. Cent.
  97. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C. 97.  et al. 2014. 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 311:507–20 [Google Scholar]
  98. 98. UK Prospective Diabetes Study Group 1998. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 317:713 [Google Scholar]
  99. Ferrari R. 99.  1997. Major differences among the three classes of calcium antagonists. Eur. Heart J. 18:Suppl. AA56–70 [Google Scholar]
  100. Fleckenstein A. 100.  1983. History of calcium antagonists. Circ. Res. 52:I3–16 [Google Scholar]
  101. Braunwald E. 101.  1982. Mechanism of action of calcium-channel-blocking agents. N. Engl. J. Med. 307:1618–27 [Google Scholar]
  102. Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J. 102.  2005. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol. Rev. 57:411–25 [Google Scholar]
  103. Nelson CR, Knapp DA. 103.  2000. Trends in antihypertensive drug therapy of ambulatory patients by US office-based physicians. Hypertension 36:600–3 [Google Scholar]
  104. Alderman MH, Cohen H, Roque R, Madhavan S. 104.  1997. Effect of long-acting and short-acting calcium antagonists on cardiovascular outcomes in hypertensive patients. Lancet 349:594–98 [Google Scholar]
  105. Pahor M, Guralnik JM, Ferrucci L, Corti MC, Salive ME. 105.  et al. 1996. Calcium-channel blockade and incidence of cancer in aged populations. Lancet 348:493–97 [Google Scholar]
  106. Rosenberg L, Rao RS, Palmer JR, Strom BL, Stolley PD. 106.  et al. 1998. Calcium channel blockers and the risk of cancer. JAMA 279:1000–4 [Google Scholar]
  107. Bonny A, Lacombe F, Yitemben M, Discazeaux B, Donetti J. 107.  et al. 2008. The 2007 ESH/ESC guidelines for the management of arterial hypertension. J. Hypertens. 26:825–26 [Google Scholar]
  108. Campbell NR, Kaczorowski J, Lewanczuk RZ, Feldman R, Poirier L. 108.  et al. 2010. 2010 Canadian Hypertension Education Program (CHEP) recommendations: the scientific summary—an update of the 2010 theme and the science behind new CHEP recommendations. Can. J. Cardiol. 26:236–40 [Google Scholar]
  109. Wang JG, Kario K, Lau T, Wei YQ, Park CG. 109.  et al. 2011. Use of dihydropyridine calcium channel blockers in the management of hypertension in Eastern Asians: a scientific statement from the Asian Pacific Heart Association. Hypertens. Res. 34:423–30 [Google Scholar]
  110. Bailey DG, Arnold JMO, Bend JR, Tran LT, Spence JD. 110.  1995. Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. Br. J. Clin. Pharmacol. 40:135–40 [Google Scholar]
  111. Sica DA. 111.  2006. Interaction of grapefruit juice and calcium channel blockers. Am. J. Hypertens. 19:768–73 [Google Scholar]
  112. Williams DM, Cubeddu LX. 112.  1988. Amlodipine pharmacokinetics in healthy volunteers. J. Clin. Pharmacol. 28:990–94 [Google Scholar]
  113. Sica DA. 113.  2001. Current concepts of pharmacotherapy in hypertension: combination calcium channel blocker therapy in the treatment of hypertension. J. Clin. Hypertens. 3:322–27 [Google Scholar]
  114. Weir MR. 114.  2003. Incidence of pedal edema formation with dihydropyridine calcium channel blockers: issues and practical significance. J. Clin. Hypertens. 5:330–35 [Google Scholar]
  115. Sica DA. 115.  2003. Calcium channel blocker-related periperal edema: Can it be resolved?. J. Clin. Hypertens. 5:291–95 [Google Scholar]
  116. Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG. 116.  et al. 1997. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 350:757–64 [Google Scholar]
  117. Wang JG, Staessen JA, Gong L, Liu L. 117.  2000. Chinese trial on isolated systolic hypertension in the elderly. Arch. Intern. Med. 160:211–20 [Google Scholar]
  118. 118. ALLHAT Off. Coord. ALLHAT Collab. Res. Group 2002. 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 288:2981–97 [Google Scholar]
  119. Hansson L, Hedner T, Lund-Johansen P, Kjeldsen SE, Lindholm LH. 119.  et al. 2000. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet 356:359–65 [Google Scholar]
  120. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P. 120.  et al. 2003. 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 290:2805–16 [Google Scholar]
  121. Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T. 121.  et al. 2003. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA 289:2073–82 [Google Scholar]
  122. Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. 122.  2009. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am. J. Med. 122:290–300 [Google Scholar]
  123. López-Sendón J, Swedberg K, McMurray J, Tamargo J, Maggioni AP. 123.  et al. 2004. Expert consensus document on β-adrenergic receptor blockers. Eur. Heart J. 25:1341–62 [Google Scholar]
  124. Dresser GK, Spence JD, Bailey DG. 124.  2000. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin. Pharmacokinet. 38:41–57 [Google Scholar]
  125. Kelly JG, O'Malley K. 125.  1992. Clinical pharmacokinetics of calcium antagonists: an update. Clin. Pharmacokinet. 22:416–33 [Google Scholar]
  126. Bailey DG, Dresser GK. 126.  2004. Interactions between grapefruit juice and cardiovascular drugs. Am. J. Cardiovasc. Drugs 4:281–97 [Google Scholar]

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