Comparing recommended doses of angiotensin receptor blockers and ACE inhibitors (CORD Study)

Aim. The CORD Study compared effectiveness and tolerability of losartan and ramipril in patients with arterial hypertension (AH).

Material and methods. The study included two groups, A and B. In Group A (n=4016; mean age 62,6+11,6 years; 53,1% women), the patients with blood pressure (BP) <160/100 mm Hg and ACE inhibitor therapy lasting for >3 months were switched from ACE inhibitors to losartan. At baseline and 1, 3, 6, and 12 months later, BP, heart rate, and biochemical parameters were measured; general blood assay and electrocardiography (ECG) were also performed. In group B (n=3813; mean age 60,5+12,2 years; 50,5% women), the patients with BP >140/90 mm Hg and no previous ACE inhibitor or angiotensin receptor blocker (ARB) therapy were randomly administered either losartan (50 mg/d; n=1887) or ramipril (5 mg/d; n=1926).

Results. Group A demonstrated a decrease in BP — from 147,4+14,8/87,7+9,3 to 139,7+11,8/83,0+9,3 mm Hg (p<0,001) after one month of the treatment, and to 133,7+11,3/79,1+7,06 mm Hg (p<0,001) after one year. Adverse effect prevalence did not increase. After one year, Group B demonstrated a reduction in BP levels — in losartan subgroup, from 156,5+13,1/93,4+8,8 to 134,55+11,3/80,16+6,6 mm Hg (p<0,001), and in ramipril subgroup — from 155,9+13,1/93,0+8,9 to 134,1+11,2/81,5+6,8 mm Hg (p<0,001). No severe adverse effects were registered, but in ramipril subgroup, cough was 8 times more prevalent.

Conclusion. ACE inhibitor substitution with losartan was safe and effective. Losartan and ramipril demonstrated equal antihypertensive effectiveness and a tendency to improve metabolic parameters. Losartan therapy was better tolerated than ramipril.

1. Task Force Members 2007. Guidelines for the management of arterial hypertension. J Hypertens 2007; 25: 1105-87.

2. Dahlof B, Devereux RB, Kjeldsen SE, for the LIFE investiga¬tors. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoints reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995-1003.

3. Dahlof B for the ASCOT investigators. Prevention of coronary 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 multicenter randomised controlled trial. Lancet 2003; 361: 1149-58.

4. Poulter NR for the ASCOT investigators. Role of blood pressure and other variables in the differential cardiovascular event rate noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-АДКЛ). Lancet 2005; 366: 907-13.

5. Julius S, Kjeldsen SE, Weber M, 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: 2022-31.

6. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomised 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: 2981-97.

7. The SOLVD investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and heart failure. N Engl J Med 1991; 325: 293-302.

8. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dys¬function after myocardial infarction: results of the Survival and Ventricular Enlargement study. N Engl J Med 1992; 327: 669¬77.

9. Flather MD, Yusuf S, Kober L, et al. Long term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunc¬tion: a systematic overview of data from individual patients. Lancet 2000; 355: 1575-81.

10. Pfeffer MA, Domanski M, Rosenberg Y, et al. Prevention of events with angiotensin-converting enzyme inhibition (the PEACE study design). Prevention of Events with Angiotensin-Converting Enzyme Inhibition. Am J Cardiol 1998; 82: 25H-30.

11. Pitt B. ACE inhibitors for patients with vascular disease without left ventricular dysfunction — may they rest in peace? N Engl J Med 2004; 351: 2115-7.

12. Yusuf S, Sleight P, Pogue J, et al. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-con¬verting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 145-53.

13. Pitt B, Segal R, Martinez FA, et al. Randomized trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly study, ELITE). Lancet 1997; 349: 747¬52.

14. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with sympto¬matic heart failure: randomized trial: the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582-7.

15. Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. New Engl J Med 2001; 345: 1667-75.

16. Dickstein K, Kjekshus J and the OPTIMAAL Study Group. Effects of losartan and captopril on mortality and morbid¬ity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet 2002; 360: 752-60.

17. Pfeffer MA, McMurray JJV, Velazquez EJ for the VALIANT Investigators. Valsartan, captopril, or both in myocardial infarc¬tion complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893-906.

18. The ONTARGET investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547-59.

19. Spinar J, Vitovec J, Spinarova L, et al. A comparison of interven¬tion with losartan or captopril in acute myocardial infarction. Eur J Heart Failure 2000; 2(1): 91-100.

20. Spinar J, Vitovec J, Pluhacek L, et al. First dose hypotension after angiotensin converting enzyme inhibitor captopril and angiotensin II blocker losartan in patients with acute myocardial infarction. Int J Cardiol 2000; 75: 197-204.

21. The EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicenter trial (the EUROPA study). Lancet 2003; 362: 782-8.

22. Pepine CJ for the INVEST Investigators. INVEST: International Verapamil SR/ Trandolapril Study. JAMA 2003; 290: 2805-16.

23. Nissen SE, Tuzcu EM, Libby P, for the CAMELOT investigators. CAMELOT (Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pres¬sure). JAMA 2004; 292: 2217-26.

24. Bakris G, Molitch M, Hewkin A, et al. Differences in glucose tolerance between fixed-dose antihypertensive drug combina¬tions in people with metabolic syndrome. Diabetes Care 2006; 29: 2592-7.

25. Dahlof B, Anderson DR, Arora V, et al. Aliskiren, a direct renin inhibitor, provides antihypertensive efficacy and excellent toler¬ability independent of age or gender in patients with hyperten¬sion. J Clin Hypertens 2007; 9 Suppl A (5): A157, P-376.

26. Mancia G, Grassi G. Systolic and diastolic blood pressure con¬trol in hypertensive drug trials. J Hypertens 2002; 20: 1461-4.

27. Benetos A, Zurek M, Morcet J, et al. A decrease in diastolic blood pressure combined with an increase in systolic blood pres¬sure is associated with a higher cardiovascular mortality in men. JACC 2000; 35: 673-80.

28. Waeber B. Targeting systolic blood pressure: the key to control¬ling combined systolic/diastolic hypertension. AHJ 2006; 19: 985-6.

29. Blacher J, Staessen JA, Girerd X, et al. Pulse pressure not mean pressure determines cardiovascular risk in elderly hypertensive patients. Arch Intern Med 2000; 160: 1085-9.

30. Staessen JA, Gasowski J, Wang JG, et al. Risk of untreated and treated isolated systolic hypertension in the elderly: meta¬analysis of outcome trials. Lancet 2000; 355: 865-72.

31. Blood Pressure Lowering Treatment Trialists’ Collaboration. Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system. J Hypertens 2007; 25(5): 951-8.

32. Veronesi M, Cicero AFG, Prandin МГ, et al. A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice. Vasc Health Risk Manag 2007; 3 (5): 1-7.