Acute coronary syndromes prevention

The major goals for the treatment of ischemic heart disease are to prevent acute coronary syndromes and death, alleviate acute symptoms of myocardial ischemia, prevent recurrent symptoms of myocardial ischemia, and avoid or minimize adverse treatment effects. 

The usefulness of LMWHs has been evaluated extensively for many indications, including acute coronary syndromes, DVT, PE, and prevention of VTE in several high-risk populations. 

Badimon JJ, Zaman A, Helft G, Fayad Z, Fuster V (1999) Acute coronary syndromes pathophysiology and preventive priorities. Thromb Haemost 82 997-1004... 

Atorvastatin, simvastatin, rosuvastatin Inhibit HMG-CoA reductase Reduce cholesterol synthesis and up-regulate low-density lipoprotein (LDL) receptors on hepatocytes modest reduction in triglycerides Atherosclerotic vascular disease (primary and secondary prevention) t acute coronary syndromes Oral duration 12-24 h Toxicity Myopathy, hepatic dysfunction Interactions CYP-dependent metabolism (3A4, 2C9) interacts with CYP inhibitors... 

Wallentin L. Prevention of cardiovascular events after acute coronary syndrome. Semin Vase Med. 2005 5 293-300. 

Platelet glycoprotein Ilb/llla (GPIIb/llla) receptor inhibitors are widely used to prevent thrombotic vascular events, especially in patients with acute coronary syndromes (ACS) or in those undergoing intravascular interventional procedures. The purpose of this chapter is to evaluate the quality and magnitude of the clinical trial evidence in support of their use, In addition, key issues regarding their optimal application in clinical practice will be discussed. 

Patients with acute coronary syndromes such as acute myocardial infarction and unstable angina remain at risk for recurrent myocardial ischemia despite therapy with antiplatelet agents and heparin. Although first clinical trials indicate a possible use of oral direct TIs for the prevention of cardiovascular events in patients after acute myocardial infarction, the presently available data are still limited and it has not... 

I The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation, N Engl J Med 2001 345 494-502. 

Peters R, Mehta SR, Fox KA, et al. Clopidogrel in unstable angina to prevent recurrent events (CURE) trial investigators. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes observations from the clopidogrel in unstable angina to prevent recurrent events (CURE) study, Circulation 2003 108(14) 1682-1687. 

These results taken together show that abciximab is an effective agent in preventing acute coronary syndromes based on its inhibition of platelet GP Ilb/IIIa and probably also of 0 3 and Mac-1, which thereby induces interference with several thrombogenic and inflammatory pathways. 

There are several new factor Xa inhibitors currently under development. One is apixaban 40 (BMS-562247), which is in Phase III clinical trials and, if approved, will be marketed by joint venture of Bristol-Myers Squibb and Pfizer for prevention of venous thromboembolism. The other factor Xa inhibitor being developed is otamixaban 41, which is being investigated by Sanofi-Aventis in Phase II clinical trials (at the time of writing) as a treatment for acute coronary syndrome. 

The term acute coronary syndrome (ACS) encompasses most of the patients defined so far in this chapter who present with unstable ischemic heart disease. Most of these syndromes occur in response to an acute event in the coronary artery when circulation to a region of the heart is obstructed. If the obstruction is high grade and persists, then necrosis usually ensues. Since necrosis takes some time to develop, it is apparent that therapy, including opening the blocked coronary artery in a timely fashion, often can prevent some of the death of myocardial tissue. These syndromes are usually, but not always, associated with chest discomfort. 

Lemmer, B. Chronopharmacological aspects for the prevention of acute coronary syndromes. Eur. Heart J. 1998, 19 (Suppl. C), C50-C58. 

This review summarizes the available morphological evidence for coronary microembolization in patients who died from coronary artery disease, most notably from sudden death. Then the experimental pathophysiology of coronary microembolization in animal models of acute coronary syndromes is detailed. Finally, the review presents the available clinical evidence for coronary microembolization in patients, highlights its key features - arrhythmias, contractile dysfunction, microinfarcts and reduced coronary reserve -, compares these features to those of the experimental model and addresses its prevention by mechanical protection devices and glycoprotein Ilb/IIIa antagonism. 

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