Unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) is a common but heterogeneous disorder with patients exhibiting widely varying risks. Early risk stratification is at the center of the management program and can be achieved using clinical criteria and biomarkers, or a combination. In addition to anti-ischemic therapy and aspirin, the thienopyridine clopidogrel is indicated except in patients who are potential candidates for urgent coronary artery bypass grafting (CABG). Platelet glycoprotein (GP) IIb/IIIa antagonists are indicated in high-risk patients likely to undergo percutaneous coronary intervention (PCI) but are not indicated in the management of lower-risk patients who do not undergo PCI. There is a growing body of evidence to support the substitution of the low-molecular-weight heparin (LMWH) enoxaparin for unfractionated heparin (UFH). Three recent trials have demonstrated the benefit of an early invasive strategy with catheterization followed by revascularization in patients at high and intermediate risk. Lower-risk patients should undergo early noninvasive stress testing. An intensive program of secondary prevention is mandatory and should be begun before hospital discharge.

Vascular inflammation is central to the pathogenesis of acute coronary syndromes (ACS) and the response to vascular injury after percutaneous coronary intervention (PCI). For both ACS and PCI, the magnitude of vascular inflammation is linked to adverse late clinical outcomes (e.g., death, recurrent myocardial infarction [MI] or ischemia, and restenosis). Many pharmacologic therapies with demonstrated efficacy for the treatment of ACS have anti-inflammatory properties, which are distinct from their perceived primary mechanism of action. The anti-inflammatory effects of aspirin, clopidogrel, low-molecular-weight heparin (LMWH), platelet glycoprotein (GP) IIb/IIIa receptor inhibitors, statins, and angiotensin converting enzyme (ACE) inhibitors are reviewed, and the hypothesis is generated that modulation of vascular inflammation at least in part contributes a common basis for the long-term clinical benefit ascribed to these medications. A therapeutic algorithm based on clinical risk stratification and coronary revascularization strategy is proposed for incorporating the current American College of Cardiology (ACC)/American Heart Association (AHA) guideline recommendations for treatment of patients who present with non-ST-elevation ACS.

Considerable new evidence has accumulated in randomized trials of myocardial reperfusion. The trials of catheter-based reperfusion compared with fibrinolytics have shown an advantage for angioplasty and stenting over pharmacologic therapy, even accounting for delays in transporting patients from facilities with intervention capabilities. On the basis of the recent trials, it is recommended that a regional center for infarct intervention be set up akin to regional trauma centers in the United States. Now that we have entered the third decade of myocardial reperfusion therapy, we can expect iterative improvement in all aspects, and ultimately a fused approach of pharmacology and mechanical therapies-to achieve the optimal outcomes and continue to lower the toll of fatality and morbidity of acute myocardial infarction (MI).

The endothelin (ET) system is comprised of 4 active ETs, with ET-1 being the predominant isoform in the cardiovascular system. Because of the potent vasoconstricting and mitogenic effects of ET-1 and its involvement in various cardiovascular diseases, blockade of the ET receptor has received considerable attention. ET receptor antagonism has been demonstrated to be beneficial in patients with pulmonary hypertension. The nonselective ET receptor antagonist bosentan improves exercise capacity and increases time to clinical worsening in patients with pulmonary arterial hypertension. The selective ET A receptor antagonist sitaxsentan also improves hemodynamics and exercise capacity in patients with pulmonary arterial hypertension. Results with ET receptor antagonists in congestive heart failure have been disappointing. Although some studies have suggested benefit, larger studies have been neutral. The use of ET receptor antagonists for other conditions has not been fully explored. Future studies with the use of ET receptor antagonists as part of a multidrug regimen are also needed.