Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction

Cardiovascular Research Unit, University of Edinburgh, United Kingdom.

OBJECTIVES. This study investigated the effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. BACKGROUND. Angiotensin-converting enzyme inhibitors reduce the incidence of acute coronary syndromes in patients with mild left ventricular dysfunction after myocardial infarction. Abnormal endogenous fibrinolysis, reflected in increased levels of endogenous tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor type 1 activity, is associated with an increased risk of myocardial infarction in patients with ischemic heart disease. METHODS. In a randomized, double-blind crossover study beginning 8 weeks after uncomplicated myocardial infarction, patients received 4 weeks of placebo and 4 weeks of captopril (75 mg daily) therapy. At the end of each treatment period, we measured t-PA antigen and plasminogen activator inhibitor type 1 antigen and activity. RESULTS. Median values in the 15 patients after placebo and in 12 normal men matched for age and body mass index were, respectively, t-PA antigen 16.0 versus 9.5 ng/ml (p = 0.001), plasminogen activator inhibitor type 1 antigen 17.3 versus 8.6 ng/ml (p = 0.29) and plasminogen activator inhibitor type 1 activity 13.2 versus 6.3 AU/ml (p = 0.04). After 4 weeks of treatment with captopril in the 15 patients, the estimated (95% confidence interval) median reduction in t-PA antigen was 7.3 ng/ml (-4.6 to -10.3 ng/ml, p = 0.001), in plasminogen activator inhibitor type 1 antigen 3.1 ng/ml (+1.5 to -8.4 ng/ml, p = 0.17) and in plasminogen activator inhibitor type 1 activity -2.2 AU/ml (-1.0 to -4.3 AU/ml, p = 0.02). CONCLUSIONS. Treatment with captopril after uncomplicated myocardial infarction is associated with a significant decrease in elevated levels of t-PA antigen and plasminogen activator inhibitor type 1 activity. This may help to explain the reduction in risk of coronary thrombosis associated with the use of angiotensin-converting enzyme inhibitors.

This article has been cited by other articles:

				A. Festa, K. Williams, R. P. Tracy, L. E. Wagenknecht, and S. M. Haffner Progression of Plasminogen Activator Inhibitor-1 and Fibrinogen Levels in Relation to Incident Type 2 Diabetes Circulation, April 11, 2006; 113(14): 1753 - 1759. [Abstract] [Full Text] [PDF]

				N. J. Brown, J. A.S. Muldowney III, and D. E. Vaughan Endogenous NO Regulates Plasminogen Activator Inhibitor-1 During Angiotensin-Converting Enzyme Inhibition Hypertension, March 1, 2006; 47(3): 441 - 448. [Abstract] [Full Text] [PDF]

				E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]

				N. L.M. Cruden, F. N. Witherow, D. J. Webb, K. A.A. Fox, and D. E. Newby Bradykinin Contributes to the Systemic Hemodynamic Effects of Chronic Angiotensin-Converting Enzyme Inhibition in Patients With Heart Failure Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1043 - 1048. [Abstract] [Full Text] [PDF]

				J. P. Tsikouris, J. A. Suarez, G. E. Meyerrose, M. Ziska, D. Fike, and J. Smith Questioning a Class Effect: Does ACE Inhibitor Tissue Penetration Influence the Degree of Fibrinolytic Balance Alteration following an Acute Myocardial Infarction? J. Clin. Pharmacol., February 1, 2004; 44(2): 150 - 157. [Abstract] [Full Text] [PDF]

				M. Pretorius, L. J. Murphey, J. A. McFarlane, D. E. Vaughan, and N. J. Brown Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass Circulation, December 23, 2003; 108(25): 3079 - 3083. [Abstract] [Full Text] [PDF]

				M. Pretorius, D. Rosenbaum, D. E. Vaughan, and N. J. Brown Angiotensin-Converting Enzyme Inhibition Increases Human Vascular Tissue-Type Plasminogen Activator Release Through Endogenous Bradykinin Circulation, February 4, 2003; 107(4): 579 - 585. [Abstract] [Full Text] [PDF]

				F. N. Witherow, P. Dawson, C. A. Ludlam, K. A. A. Fox, and D. E. Newby Marked bradykinin-induced tissue plasminogen activator release in patients with heart failure maintained on long-term angiotensin-converting enzyme inhibitor therapy J. Am. Coll. Cardiol., September 4, 2002; 40(5): 961 - 966. [Abstract] [Full Text] [PDF]

				J. G F Cleland, J. John, J. Dhawan, and A. Clark What is the optimal medical management of ischaemic heart failure? Br. Med. Bull., October 1, 2001; 59(1): 135 - 158. [Abstract] [Full Text] [PDF]

				S. Kennon, K. Barakat, G. A. Hitman, C. P. Price, P. G. Mills, K. Ranjadayalan, J. Cooper, H. Clark, and A. D. Timmis Angiotensin-converting enzyme inhibition is associated with reduced troponin release in non-ST-elevation acute coronary syndromes J. Am. Coll. Cardiol., September 1, 2001; 38(3): 724 - 728. [Abstract] [Full Text] [PDF]

				N. J. Brown, L. J. Murphey, N. Srikuma, N. Koschachuhanan, G. H. Williams, and D. E. Vaughan Interactive Effect of PAI-1 4G/5G Genotype and Salt Intake on PAI-1 Antigen Arterioscler Thromb Vasc Biol, June 1, 2001; 21(6): 1071 - 1077. [Abstract] [Full Text] [PDF]

				K. Minai, T. Matsumoto, H. Horie, N. Ohira, H. Takashima, H. Yokohama, and M. Kinoshita Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1565 - 1570. [Abstract] [Full Text] [PDF]

				C. Labinjoh, D. E. Newby, P. Dawson, N. R. Johnston, C. A. Ludlam, N. A. Boon, and D. J. Webb Fibrinolytic actions of intra-arterial angiotensin II and bradykinin in vivo in man Cardiovasc Res, September 1, 2000; 47(4): 707 - 714. [Abstract] [Full Text] [PDF]

				L. Tarnow, C. D. A. Stehouwer, J. J. Emeis, O. Poirier, F. Cambien, B. V. Hansen, and H.-H. Parving Plasminogen activator inhibitor-1 and apolipoprotein E gene polymorphisms and diabetic angiopathy Nephrol. Dial. Transplant., May 1, 2000; 15(5): 625 - 630. [Abstract] [Full Text] [PDF]

				N. J. Brown, M. Agirbasli, and D. E. Vaughan Comparative Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Antagonism on Plasma Fibrinolytic Balance in Humans Hypertension, August 1, 1999; 34(2): 285 - 290. [Abstract] [Full Text] [PDF]

				N. E. R. Goodfield, D. E. Newby, C. A. Ludlam, and A. D. Flapan Effects of Acute Angiotensin II Type 1 Receptor Antagonism and Angiotensin Converting Enzyme Inhibition on Plasma Fibrinolytic Parameters in Patients With Heart Failure Circulation, June 15, 1999; 99(23): 2983 - 2985. [Abstract] [Full Text] [PDF]

				E. M Lonn and S. Yusuf Evidence based cardiology: Emerging approaches in preventing cardiovascular disease BMJ, May 15, 1999; 318(7194): 1337 - 1341. [Full Text]

				J. W. Sayer, C. Gutteridge, D. Syndercombe-Court, P. Wilkinson, and A. D. Timmis Circadian activity of the endogenous fibrinolytic system in stable coronary artery disease: effects of beta-adrenoreceptor blockers and angiotensin-converting enzyme inhibitors J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1962 - 1968. [Abstract] [Full Text] [PDF]

				N. J. Brown, M. A. Agirbasli, G. H. Williams, W. R. Litchfield, and D. E. Vaughan Effect of Activation and Inhibition of the Renin-Angiotensin System on Plasma PAI-1 Hypertension, December 1, 1998; 32(6): 965 - 971. [Abstract] [Full Text] [PDF]

				H. Tomiyama, Y. Kimura, H. Mitsuhashi, T. Kinouchi, H. Yoshida, T. Kushiro, and N. Doba Relationship Between Endothelial Function and Fibrinolysis in Early Hypertension Hypertension, January 1, 1998; 31(1): 321 - 327. [Abstract] [Full Text] [PDF]

				D.-K. Kim, J.-W. Kim, S. Kim, H.-C. Gwon, J.-C. Ryu, J.-E. Huh, J.-A Choo, Y. Choi, C.-H. Rhee, and W.-R. Lee Polymorphism of Angiotensin Converting Enzyme Gene Is Associated With Circulating Levels of Plasminogen Activator Inhibitor-1 Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3242 - 3247. [Abstract] [Full Text]

				D. E. Vaughan, J.-L. Rouleau, P. M. Ridker, J. M. O. Arnold, F. J. Menapace, and M. A. Pfeffer Effects of Ramipril on Plasma Fibrinolytic Balance in Patients With Acute Anterior Myocardial Infarction Circulation, July 15, 1997; 96(2): 442 - 447. [Abstract] [Full Text]

				I. Seljeflot, A. Moan, S. Kjeldsen, E. Sandvik, and H. Arnesen Effect of Angiotensin II Receptor Blockade on Fibrinolysis During Acute Hyperinsulinemia in Patients With Essential Hypertension Hypertension, June 1, 1996; 27(6): 1299 - 1304. [Abstract] [Full Text]

				H. J. Dargie Prof. and J. Byrne Pathophysiological Aspects of the Renin-Angiotensin-Aldosterone System in Acute Myocardial Infarction European Journal of Cardiovascular Prevention & Rehabilitation, October 1, 1995; 2(5): 389 - 395. [Abstract] [PDF]

				G. Rossi, A. Rossi, A. Sacchetto, E. Pavan, and A. C. Pessina Hypertensive Cerebrovascular Disease and the Renin-Angiotensin System Stroke, September 1, 1995; 26(9): 1700 - 1706. [Abstract] [Full Text]

				E. Falk, P. K. Shah, and V. Fuster Coronary Plaque Disruption Circulation, August 1, 1995; 92(3): 657 - 671. [Full Text]

				A. J. Drake-Holland Modification of Coronary Artery Disease Using Antithrombotic Therapy European Journal of Cardiovascular Prevention & Rehabilitation, June 1, 1995; 2(3): 229 - 233. [Abstract] [PDF]