Abstract
Evidence now exists suggesting a pathologic role for angiotensin II in patients with cardiovascular disease and those with risk factors. Clinical trials such as the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE), the Heart Outcomes Prevention Evaluation Study (HOPE), the African American Study of Kidney Disease and Hypertension (AASK), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study have clearly demonstrated that blood pressure reduction is important in hypertension and diabetes. If this can be accomplished with agents that block the renin‐angiotensin system, then additional clinical benefit will be achieved. Clinical data on angiotensin‐converting enzyme inhibitors (ACEIs) are well established, while emerging data on the use of angiotensin II receptor blockers (ARBs) continue to grow. There is evidence supporting the concept of angiotensin II escape in the presence of ACEIs. The question that remains to be answered is whether a combination of both agents (ACEIs and ARBs) can improve clinical outcomes. Ongoing clinical trials will answer this question.
Keywords: angiotensin II, hypertension, diabetes
Full Text
The Full Text of this article is available as a PDF (18.6 KB).
References
- 1. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157: 2413–2446 [DOI] [PubMed] [Google Scholar]
- 2. Dzau V, Braunwald E: Resolved and unresolved issues in the prevention and treatment of coronary artery disease: A workshop consensus statement. Am Heart J 1991; 121: 1244–1263 [DOI] [PubMed] [Google Scholar]
- 3. Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC, Klein M, Lamas GA, Packer M, Rouleau J, Rouleau JL, Rutherford J, Wertheimer JH, Hawkins CM: Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327: 669–677 [DOI] [PubMed] [Google Scholar]
- 4. Neal B, MacMahon S, Chapman N: Effects of ACE inhibitors, calcium antagonists, and other blood‐pressure‐lowering drugs: Results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Collaboration. Lancet 2000; 356: 1955–1964 [DOI] [PubMed] [Google Scholar]
- 5. Dahlof B, Devereux RB, Kjelsden SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe‐Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H:. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet 2002; 359: 995–1003 [DOI] [PubMed] [Google Scholar]
- 6. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G: Effects of an angiotensin‐converting‐enzyme inhibitor, ramipril, on cardiovascular events in high‐risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145–153 [DOI] [PubMed] [Google Scholar]
- 7. Svensson P, de Faire U, Sleight P, Yusuf S, Östergren J: Comparative effects of ramipril on ambulatory and office blood pressures. A HOPE substudy. Hypertension 2001; 38: e28–e32 [DOI] [PubMed] [Google Scholar]
- 8. Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmaki K, Dahlof B, de Faire U, Morlin C, Karlberg BE, Wester PO, Bjorck JE: Effect of angiotensin‐converting‐enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: The Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999; 353: 611–616 [DOI] [PubMed] [Google Scholar]
- 9. Carlsson PO, Berne C, Jansson L: Angiotensin II and the endocrine pancreas: Effects on islet blood flow and insulin secretion in rats. Diabetologia 1998; 41: 127–133 [DOI] [PubMed] [Google Scholar]
- 10. Brenner BM, Cooper ME, de Zeeuw D, Keene WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–869 [DOI] [PubMed] [Google Scholar]
- 11. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I: Renoprotective effect of the angiotensin‐receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–860 [DOI] [PubMed] [Google Scholar]
- 12. Exner DV, Dries DL, Domanski MJ, Cohn JN: Lesser response to angiotensin‐converting‐enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med 2001; 344: 1351–1357 [DOI] [PubMed] [Google Scholar]
- 13. Agodoa LY, Appel L, Bakris GL, Beck G, Bourgoignie J, Briggs JP, Charleston J, Cheek D, Cleveland W, Douglas JG, Douglas M, Dowie D, Faulkner M, Gabriel A, Gassman J, Greene T, Hall Y, Hebert L, Hiremath L, Jamerson K, Johnson CJ, Lopple J, Kusek J, Lash J, Lea J, Lewis JB, Lipkowitz M, Massry S, Middleton J, Miller ER III, Norris K, O'Connor D, Ojo A, Phillips RA, Pogue V, Rahman M, Randall OS, Rostand S, Schulman G, Smith W, Thornley‐Brown D, Tischer CC, Toto RD, Wright JT Jr, Xu S: Effect of ramipril vs. amlodipine on renal outcomes in hypertensive nephrosclerosis: A randomized controlled trial. J Am Med Assoc 2001; 285: 2719–2728 [DOI] [PubMed] [Google Scholar]
- 14. Heart Outcomes Prevention Evaluation Study Investigators : Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE study and MICRO‐HOPE substudy. Lancet 2000; 355: 253–259 [PubMed] [Google Scholar]
- 15. UK Prospective Diabetes Study Group : Tight blood pressure control and risk of macrovascular and microvascular complication in type 2 diabetes: UKPDS 38. Br Med J 1998; 317: 703–713 [PMC free article] [PubMed] [Google Scholar]
- 16. Tang WH, Vagelos RH, Yee YG, Benedict CR, Willson K, Liss CL, Fowler MB: Neurohormonal and clinical responses to high‐versus low‐dose enalapril therapy in chronic heart failure. J Am Coll Cardiol 2002; 39: 70–78 [DOI] [PubMed] [Google Scholar]
- 17. Cohn JN, Tognoni G: A randomized trial of the angiotensin‐receptor block‐ervalsartan in chronic heart failure. N Engl J Med 2001; 345: 1667–1675 [DOI] [PubMed] [Google Scholar]