Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Prothrombotic Processes and Myocardial Infarction Risk

Abstract

Acute ischemic events occur most frequently at dawn and in the early hours of the morning. The development of these severe clinical events exhibits a temporal relationship with changes in various hemodynamic, prothrombotic, and hormonal processes. The authors highlight not only these relationships but also the potential protective effect of increased bradykinin levels and the inhibition of different angiotensin II (AT-II) receptors (AT2, AT4) against unfavorable prothrombotic influences, which-based on studies to date-decreases the risk of acute cardiovascular events. Comparisons are presented between the different effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on factors that influence thrombus formation and myocardial infarction risk.

Fig. 1

Circadian rhythm of coronary heart disease mortality and acute myocardial infarction that shows a significant peak primarily in the period between 6 a.m. and 8 a.m. [–8]. CHD coronary heart disease

Fig. 2

Circadian rhythm of elements of the fibrinolytic system (plasminogen activator inhibitor [PAI]-1, tissue plasminogen activator [t-PA]) that represents a critical period for acute cardiovascular events [–18]

Fig. 3

Potential conjunction of triggers (workload, stress, sadness/anger) and acute risk factors (hemodynamic effects, prothrombotic conditions, inflammatory reactions, and neurohormonal influences) that were ‘superposed’ to disorders already caused by the chronic risk factors and initiate the acute coronary events [13]. BP blood pressure, CNS central nervous system, HR heart rate, PAI-1 plasminogen activator inhibitor-1

Fig. 4

Presumed differences in mechanisms of action of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. The elevated levels of plasminogen activator inhibitor-1 and decreased tissue plasminogen activator activity affects coronary circulation, causing coronary heart disease. Evidence suggests that bradykinin (that increased by angiotensin-converting enzyme inhibitors only) stimulates tissue plasminogen activator synthesis and AT4 receptors (that is inhibited by angiotensin-converting enzyme inhibitors only also) results in increased expression of plasminogen activator inhibitor-1 secretion in endothelial cells. This mode of action of angiotensin-converting enzyme inhibitors explains their ability to reduce acute coronary events [–27]. ACE(I) angiotensin-converting enzyme (inhibitor), AT angiotensin, NO nitric oxide, PAI-1 plasminogen activator inhibitor-1, PGI ₂, prostaglandin I₂, t-PA tissue plasminogen activator

Fig. 5

Different effects of the angiotensin-converting enzyme inhibitor perindopril and the angiotensin receptor blocker losartan on factors influencing thrombus formation [–39]. NS not significant, PAI-1 plasminogen activator inhibitor-1, t-PA tissue plasminogen activator

Fig. 6

Different effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of myocardial infarction compared with placebo or active compounds in some clinical trials [–47]. AMI acute myocardial infarction, CCB calcium channel blocker, CI confidence interval, HR hazard ratio