Studies on stable angina pectoris : risk indicators, prognosis and effects of verapamil or metoprolol treatment

Abstract

Hemostatic and fibrinolytic variables, inflammatory parameters, catecholamines and lipid parameters were studied at baseline, in a long-term prospective study of 809 patients with stable angina pectoris, and compared to results obtained in healthy control subjects (n=50). The prognostic implications of the various parameters at baseline were evaluated, as well as possible influences of drug treatment on these variables and their prognostic implications were studied. In addition, ultrasonographic assessments of intima-media thickness and the presence of plaques in the carotid and or femoral arteries were made at baseline, and related to cardiovascular prognosis. Clinical outcome and effects of antiangial drug treatment with metoprolol or verapamil on the prognosis of the patients were evaluated after a median follow-up time of 3.4 years.

The patients had a more atherogenic lipid profile, and had signs of disturbed fibrinolysis, both at rest and in response to exercise, compared to healthy control subjects. Furthermore, they had signs of enhanced inflammatory activity. B-thromboglobulin excretion (a marker of platelet function) in urine did not differ. Female patients had signs of increased platelet activity, a less atherogenic lipid profile, and lower inflammatory activity than male patients. Thus platelet activation may be more important in female than in male angina patients. Several of the above-mentioned variables were found to be predictors of cardiovascular events. Plasma tPA-ag at rest, and in males both tPA-ag and PAI-I activity were independent predictors of cardiovascular (CV) death or non-fatal myocardial infarction (Ml). An impaired fibrinolytic response to exercise is a new factor related to CV prognosis. This suggests that impaired fibrinolytic capacity is of importance in angina pectoris. Apolipoprotein A-I was independently related to the risk of CV death or non-fatal Ml. Both apo A-I and apo B were independent predictors of revascularization. Assessments of apolipoproteins provided better prognostic information than other lipid parameters and are to be preferred for risk evaluation. Fibrinogen and white blood cell counts were independent predictors of the risk of CV death or non-fatal Ml and of the risk of revascularization. Orosomucoid predicted the risk of revascularization. This indicates that inflammatory activity may be involved in disease progression. Metoprolol and verapamil had differential effects on lipid parameters, with a shift towards a more atherogenic lipid profile among metoprolol treated patients. However, there was no significant impact of the treatment given, or of these effects on the risk of CV events. Platelet aggregability in vivo, as assessed by filtragometry ex vivo, was attenuated by 1 month's treatment with verapamil but not by metoprolol. No important influences of drug treatment on the other parameters above were found.

Ultrasonographic assessments of IMT in the carotid and femoral artery provided some prognostic information for the risk of CV events. Carotid IMT was a weak predictor of events but femoral IMT predicted the risk of revascularization. Evaluations of plaques provided better prognostic information than assessments of IMT, suggesting a closer relationship for plaques than for IMT to coronary anatomy. Plaques in the carotid artery were related to CV death or non-fatal Ml, whereas femoral plaques were related to revascularization. No significant difference in cardiovascular prognosis during long-term treatment with metoprolol or verapamil was observed, in terms of fatal and non-fatal events. The cardiovascular event rate was much lower in females than in males. The overall prognosis was relatively good and the drugs were equally safe and well tolerated. The choice of drug treatment between metoprolol and verapamil in patients with stable angina pectoris, could thus be based more on clinical characteristics of the individual patient.