Short-term comparative outcomes associated with the use of GP IIb/IIIa antagonists in patients undergoing coronary intervention.

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists reduce the occurrence of death, myocardial infarction (MI) and urgent revascularization among patients undergoing percutaneous coronary intervention (PCI). Despite a similar mechanism of platelet inhibition, the three currently approved agents vary widely in cost. PURPOSE: The purpose of this prospectively designed, retrospective analysis was to determine clinical outcomes for patients receiving abciximab, tirofiban or eptifibatide as adjunctive therapy during PCI at a single center. We hypothesized that there would be no difference in outcomes during hospitalization following PCI in patients receiving tirofiban or eptifibatide compared with those patients who received abciximab. Outcomes examined included in-hospital mortality, hemorrhagic procedural complications, need for recatheterization, peak creatine kinase following intervention and length of hospital stay (LOS). RESULTS: Two hundred and sixty seven consecutive patients in whom GP IIb/IIIa antagonist therapy was initiated in the catheterization laboratory for PCI were analyzed. Abciximab-treated patients were more likely to be undergoing primary (p<0.001) and rescue (p=0.022) PCI and to have received fibrinolytic therapy (p=0.013) when compared to patients receiving tirofiban or eptifibatide. There were no significant differences between abciximab- and non abciximab-treated patients in either the primary PCI or non primary PCI groups in any of the studied endpoints. In patients undergoing primary PCI, abciximab-treated patients when compared with non abciximab-treated patients exhibited a trend toward an increase in hospital LOS (7.8+/-7.0 d vs 6.2+/-3.9, p=0.19) and in the frequency of hemorrhagic complications (22.1% vs 5.3%, p=0.11). In patients not receiving fibrinolytic therapy, abciximab-treated patients experienced a trend toward increased hemorrhagic complications following PCI when compared to non abciximab-treated patients (10.2% vs 6.0%, p=0.28). Complications distant from the vascular access site comprised 62.5% of hemorrhagic complications in the abciximab-treated group, but only 20% of the complications in the non-abciximab treated population (p<0.001). These data suggest no differences in acute outcomes between groups of patients receiving abciximab or other approved GP IIb/IIIa antagonists highlighting a potential significant cost saving. These data will require interpretation following the publication of comparative trials.

Effects of renal neutral endopeptidase inhibition on sodium excretion, renal hemodynamics and neurohormonal activation in patients with congestive heart failure.

We investigated the effects of inhibiting endogenous atrial natriuretic factor (ANF) metabolism on renal hemodynamics, sodium excretion and neurohormones in 12 patients with New York Heart Association functional class II congestive heart failure (CHF) due to left ventricular systolic dysfunction. In a randomized, placebo-controlled, double-blinded fashion, 8 patients received a single oral dose of candoxatril, an inhibitor of renal neutral endopeptidase, and 4 patients received placebo. Candoxatril treatment increased plasma ANF by 70 +/- 71 pg/ml (p < 0.015 vs. placebo) and plasma cGMP by 7.9 +/- 2.7 pmol/ml (p < 0.001 vs. placebo), with maximal effects at 3.5 h. Urinary cGMP more than doubled (p = 0.025 vs. placebo). Candoxatril increased urinary sodium by 2.7 +/- 2.0 mEq/h (p < 0.05 vs. placebo) and significantly elevated filtration fraction with no significant effect on glomerular filtration rate, renal plasma flow or lithium clearance. A significant reduction in aldosterone concentration with a similar trend in plasma renin activity was noted in candoxatril-treated patients. Thus in patients with moderate heart failure, renal neutral endopeptidase inhibition increases urinary sodium excretion. The lack of an effect on renal hemodynamics suggests that this natriuresis results from ANF-mediated inhibition of tubular sodium reabsorption. These findings justify additional investigation into potential clinical benefit of endopeptidase inhibition in patients with CHF.

Heart failure in women.

Observational and other studies suggest gender-related differences in the incidence and prognosis of heart failure. Women appear to live longer after the diagnosis of heart failure when compared with men. After myocardial infarction, women seem more likely than men to exhibit clinical heart failure. Diabetes appears to promote heart failure to a greater extent in women than in men. Review of data from clinical and epidemiologic studies suggests that men and women may differ in their myocardial adaptation to a variety of cardiac insults. Future investigation is necessary to better define gender-related differences and possible sex-specific therapies for those diseases resulting in heart failure.

Congestive heart failure in women: focus on heart failure due to coronary artery disease and diabetes.

Congestive heart failure (CHF) is an important clinical syndrome. Evidence from several observational studies suggests sex-related differences in the incidence and prognosis of CHF, particularly in the setting of coronary artery disease. Women appear to be more prone than men to develop heart failure late after myocardial infarction as well as in the peri-infarction period. Additionally, diabetes mellitus appears to promote heart failure to a greater extent in women than in men.

How effective is digitalis in the treatment of congestive heart failure?

The evidence suggests that digitalis glycosides do indeed improve ventricular performance through a sustained but moderate positive inotropic effect. This effect is more marked in failing than in nonfailing myocardium. The clinical studies suggest a moderate salutary effect in patients with chronic CHF who are in sinus rhythm. The drug can be given safely to patients with CAD and in combination with other medications when the physician is aware of those factors leading to increased sensitivity to digitalis.

Use of sequential cardiac enzyme analysis in stratification of risk for myocardial infarction in patients with unstable angina.

Patients presenting to the emergency room with unstable angina are a challenge to physicians whose responsibility it is to ration access to coronary care unit beds, a resource that is often in short supply. In this study, initial cardiac enzyme analysis was not helpful in identifying patients having an acute myocardial infarction. However, using two enzyme determinations, performed at least six hours apart, we were able to identify a large percentage of our patients with unstable angina who were at low risk for myocardial infarction. Patients with two consecutive normal creatinine kinase levels had only a 2% chance of having an acute myocardial infarction. We believe these data can assist physicians where monitored beds are in short supply to make judicious use of this limited resource; the subsequent reduction in critical care unit admissions and duration of stay could result in substantial monetary savings.