Oral glycoprotein IIb/IIIa antagonism in patients with coronary artery disease.

Dose-finding studies and trials of interaction of oral glycoprotein IIb/IIIa antagonists with other antiplatelet agents have been limited. We hypothesized that these detailed assessments could be first performed in patients with stable coronary artery disease (CAD) and then extrapolated to the target population. To this end, we performed 2 sequential studies. The first study examined the dose-related effects on indexes of platelet and vascular function induced by the oral inhibitor RPR 109891, when given alone and in combination with aspirin, in patients (n = 100) with stable CAD. The second study (the Antagonism of the FIbrinogen Receptor after Myocardial Events trial) assessed the pharmacodynamics and safety of derived regimens in patients (n = 320) with unstable coronary syndromes. In patients with stable CAD, platelet aggregation was dose dependently inhibited by RPR 109891, and the dose-response relation was shifted to the right by the concomitant administration of aspirin (p = 0.0001). The degree of platelet inhibition induced by 3 doses of RPR 109891 (plus aspirin) was lower in patients with unstable than stable CAD. No drug-related major bleeding occurred in either study. RPR 109891 treatment was associated with acute and delayed thrombocytopenia. In conclusion, chronic treatment with an oral glycoprotein IIb/IIIa antagonist (1) induces antiplatelet effects that are potentiated by concomitant administration of aspirin, (2) may require dose adjustment in syndromes of platelet activation, (3) is associated with a low rate of clinically significant bleeding when doses inducing incomplete inhibition of platelet aggregation are used, and (4) requires frequent monitoring of platelet count unless reliable predictors of delayed thrombocytopenia become available.

Mitral valve repair is superior to valve replacement for the early preservation of cardiac function: relation of ventricular geometry to function.

The immediate effect or mitral valve repair (MVP) or replacement (MVR) on cardiac function was compared in patients with mitral regurgitation in relation to the changes in left ventricular (LV) function and geometry by using intraoperative transesophageal echocardiography in 29 patients with MVP and 21 patients with MVR, before and immediately after cardiopulmonary bypass. The LV volumes, ejection fraction, and long-axis and short-axis lengths and eccentricity index (ratio of long axis to short axis) at end-systole and end-diastole were measured. After both MVP and MVR, there were significant decreases in LV end-diastolic volume (p < 0.0001). However, the ejection fraction did not change after MVP, whereas it decreased after MVR (p < 0.0001). After MVP, there was an increase in eccentricity index at end-systole (p < 0.0001). After MVR, there was no decrease in end-systolic volume, and the eccentricity index was lower than that after MVP (p < 0.0001). The change in LV ejection fraction correlated with the changes in eccentricity index at end-systole (r = 0.55; p < 0.0001) and end-diastole (r = 0.42; p < 0.0003). Immediate intraoperative LV function is preserved after MVP but is depressed after MVR for mitral regurgitation. The changes in ejection fraction correlate with changes in ventricular geometry.

Improved survival with coronary bypass surgery in patients with three-vessel coronary disease and abnormal left ventricular function. Matched case-control study in patients with potentially operable disease.

Recent studies have suggested that patients with three-vessel coronary disease and abnormal left ventricular function have better survival rates with bypass surgery than with medical therapy alone. Case-control studies may give accurate survival estimates, but to be valid, selection biases must be taken into account. A matched case-control method was used to compare survival patterns in patients treated medically or surgically during the 1980s. Fifty medical patients with potentially operable coronary disease and 46 surgical patients were matched for significant three-vessel disease and abnormal ventricular function. These two groups had no significant differences with regard to 24 variables, including age (64 +/- 8 versus 63 +/- 10 years), chest pain class, congestive heart failure signs, ejection fraction (36 +/- 8 versus 37 +/- 9 percent), segmental wall score, or a coronary score evaluating lesion site and severity. There were slight differences between the two groups with regard to congestive heart failure symptoms (p = 0.04). Patients undergoing bypass surgery had improved four-year survival rates compared with the medical group (89 versus 55 percent; p = 0.01). Thus, this study used an effective case-control method to suggest that, in the 1980s, coronary surgery improves prognosis substantially in surgically approachable patients with severe coronary disease and ventricular dysfunction.

Medical and surgical survival in coronary artery disease in the 1980s.

The survival of 1,657 patients with angiographically proved coronary artery disease (CAD) was studied for 4 years (mean 2.0 +/- 1.2) during the 1980s to examine the prognostic importance of multiple clinical variables. One hundred of the 1,049 medically treated patients (9.5%) and 31 of the 608 surgically treated patients (5.1%) died. Multivariate analyses revealed that the strongest prognostic variables for survival in the medical group were indexes of left ventricular function (p less than 0.0001), severity of coronary stenoses (p less than 0.0001) and age (p = 0.005). However, only age (p less than 0.0001) was a significant prognostic variable in the surgically treated group. This study emphasizes the lack of prognostic significance of left ventricular function indexes and severity of coronary stenoses in surgically treated patients with CAD. These results continue the trend toward improved surgical survival shown in recent years.