Effects of Aliskiren on the Fibrinolytic System in Patients with Coronary Artery Disease Receiving Angiotensin-converting Enzyme Inhibitor or Angiotensin II Type 1 Receptor Blocker

Overview

Journal Heart Vessels

Specialty Cardiology & Vascular Diseases

Date 2011 Nov 3

PMID 22045153

Citations 4

Authors

Ken Ishibashi

Satoshi Kurisu

Yasuko Kato

Naoya Mitsuba

Yoshihiro Dohi

Kenji Nishioka

Yasuki Kihara

Affiliations

Soon will be listed here.

Abstract

Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. We evaluated the effects of aliskiren on the fibrinolytic system in patients with coronary artery disease who were receiving angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). We studied 17 patients with coronary artery disease whose systolic blood pressure was more than 130 mmHg despite treatment with ACEIs or ARBs. Aliskiren (150 mg) was added to ACEIs or ARBs, and was continued for 6 weeks. Aliskiren significantly decreased systolic blood pressure (140 ± 6-128 ± 8 mmHg, P < 0.001) and plasma renin activity (1.8 ± 2.3-0.6 ± 0.9 ng/ml/h, P < 0.01) after 6 weeks. However, it did not affect plasminogen activator inhibitor-1 (28.8 ± 14.5-30.6 ± 13.6 ng/ml, P = 0.84), fibrinogen (305 ± 72 vs 301 ± 71 mg/dl, P = 0.33), or D-dimer (0.49 ± 0.24-0.51 ± 0.28 μg/ml, P = 0.70) levels. Our data suggested that patients receiving ACEIs or ARBs would not be expected to have any changes in biomarkers of the fibrinolytic system with additional pharmacologic inhibition of the renin-angiotensin-aldosterone system.

Citing Articles

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References

Strauss M, Hall A . Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox. Circulation. 2006; 114(8):838-54. DOI: 10.1161/CIRCULATIONAHA.105.594986. View

Uresin Y, Taylor A, Kilo C, Tschope D, Santonastaso M, Ibram G . Efficacy and safety of the direct renin inhibitor aliskiren and ramipril alone or in combination in patients with diabetes and hypertension. J Renin Angiotensin Aldosterone Syst. 2008; 8(4):190-8. DOI: 10.3317/jraas.2007.028. View

OBrien E, Barton J, Nussberger J, Mulcahy D, Jensen C, Dicker P . Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker. Hypertension. 2006; 49(2):276-84. DOI: 10.1161/01.HYP.0000253780.36691.4f. View

Pfeffer M, Braunwald E, Moye L, Basta L, Brown Jr E, Cuddy T . 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(10):669-77. DOI: 10.1056/NEJM199209033271001. View

Brown N, Agirbasli M, Vaughan D . Comparative effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on plasma fibrinolytic balance in humans. Hypertension. 1999; 34(2):285-90. DOI: 10.1161/01.hyp.34.2.285. View

McKelvie R, Yusuf S, Pericak D, Avezum A, Burns R, Probstfield J . Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation. 1999; 100(10):1056-64. DOI: 10.1161/01.cir.100.10.1056. View

Brown N, Agirbasli M, Williams G, Litchfield W, Vaughan D . Effect of activation and inhibition of the renin-angiotensin system on plasma PAI-1. Hypertension. 1998; 32(6):965-71. DOI: 10.1161/01.hyp.32.6.965. View

Hirschl M, Bur A, Woisetschlaeger C, Derhaschnig U, Laggner A . Effects of candesartan and lisinopril on the fibrinolytic system in hypertensive patients. J Clin Hypertens (Greenwich). 2007; 9(6):430-5. PMC: 8110061. DOI: 10.1111/j.1524-6175.2007.06506.x. View

Madoiwa S, Nunomiya S, Ono T, Shintani Y, Ohmori T, Mimuro J . Plasminogen activator inhibitor 1 promotes a poor prognosis in sepsis-induced disseminated intravascular coagulation. Int J Hematol. 2006; 84(5):398-405. DOI: 10.1532/IJH97.05190. View

10.

Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M . Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 2005; 111(8):1012-8. DOI: 10.1161/01.CIR.0000156466.02908.ED. View

11.

Hirohata A, Yamamoto K, Miyoshi T, Hatanaka K, Hirohata S, Yamawaki H . Impact of olmesartan on progression of coronary atherosclerosis a serial volumetric intravascular ultrasound analysis from the OLIVUS (impact of OLmesarten on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) trial. J Am Coll Cardiol. 2010; 55(10):976-82. DOI: 10.1016/j.jacc.2009.09.062. View

12.

Ono T, Sogabe M, Ogura M, Furusaki F . Automated latex photometric immunoassay for total plasminogen activator inhibitor-1 in plasma. Clin Chem. 2003; 49(6 Pt 1):987-9. DOI: 10.1373/49.6.987. View

13.

Fujita M, Sasayama S, Terasaki F, Mitani S, Morimoto T, Yamazaki T . Treatment effects of renin-angiotensin system inhibitor and calcium channel blocker in patients with coronary artery narrowing (from the Japanese Coronary Artery Disease Study). Heart Vessels. 2010; 25(6):453-9. DOI: 10.1007/s00380-010-0012-5. View

14.

Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I . Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008; 372(9644):1174-83. DOI: 10.1016/S0140-6736(08)61242-8. View

15.

Chen H, Tan H, Yang Y, Qiu L, Liu X . Effects of ramipril on serum monocyte chemoattractant protein 1, interleukin-18, and interleukin-10 in elderly patients with acute coronary syndrome. Heart Vessels. 2010; 25(2):77-81. DOI: 10.1007/s00380-009-1162-1. View

16.

Brown M, McInnes G, Papst C, Zhang J, MacDonald T . Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial. Lancet. 2011; 377(9762):312-20. DOI: 10.1016/S0140-6736(10)62003-X. View

17.

Fox K . Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003; 362(9386):782-8. DOI: 10.1016/s0140-6736(03)14286-9. View

18.

Mooser V, Nussberger J, Juillerat L, Burnier M, Waeber B, Bidiville J . Reactive hyperreninemia is a major determinant of plasma angiotensin II during ACE inhibition. J Cardiovasc Pharmacol. 1990; 15(2):276-82. DOI: 10.1097/00005344-199002000-00015. View

19.

Sato A, Saruta T . Aldosterone breakthrough during angiotensin-converting enzyme inhibitor therapy. Am J Hypertens. 2003; 16(9 Pt 1):781-8. DOI: 10.1016/s0895-7061(03)00913-0. View

20.

Brown N, Kumar S, Painter C, Vaughan D . ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time. Hypertension. 2002; 40(6):859-65. DOI: 10.1161/01.hyp.0000040264.15961.48. View