Clopidogrel in the treatment of ischaemic heart disease

Clopidogrel is an effective antiplatelet agent that has undergone rigorous assessment in the setting of ischaemic heart disease over the last decade. There is extensive evidence for the use of this drug in patients undergoing percutaneous coronary intervention, in those with stable ischaemic heart disease and also in those with acute coronary syndromes. This article examines the use of clopidogrel in patients with ischaemic heart disease.     

Clopidogrel in the treatment of ischaemic heart disease

Clopidogrel is an effective antiplatelet agent that has undergone rigorous assessment in the setting of ischaemic heart disease over the last decade. There is extensive evidence for the use of this drug in patients undergoing percutaneous coronary intervention, in those with stable ischaemic heart disease and also in those with acute coronary syndromes. This article examines the use of clopidogrel in patients with ischaemic heart disease.     

Systolic time intervals during long-term beta-blockade with alprenol in ischaemic heart disease

The effect of long-term treatment with alprenolol on left ventricular function was investigated in a controlled double-blind study of 15 patients with ischaemic heart disease (alprenolol 6, placebo 9), by measurement of systolic time intervals (STI). Significant prolongation of QS2I was observed in patients treated with alprenolol (p less than 0.05), while changes in PEPI, LVETI and PEP/LVET were all insignificant. The heart rate x systolic blood pressure product (RPP) was significantly reduced in the alprenolol group (p less than 0.05). The data suggest that long-term treatment with alprenolol did not impair left ventricular function as evaluated by STI, and that myocardial oxygen demand, assessed by RPP, was reduced during the treatment.     

Atenolol and ischaemic heart disease: an overview.

Data generated to date on the use of beta-blockers, especially atenolol, in ischaemic heart disease are reviewed and compared with the results available with the calcium antagonists. Atenolol appears to be effective as an anti-ischaemic agent in patients with obstructive coronary artery disease when reduction in myocardial oxygen supply (ischaemia not preceded by an increase in heart rate and due presumably to functional coronary stenosis) or increase in demand are the likely causes. Based on current concepts and available data, there is convincing evidence to support the use of atenolol across the spectrum of ischaemic heart disease. In contrast, results with the calcium antagonists have been disappointing and variable. Atenolol, to date, is the only beta-blocker which has been demonstrated to have a life-saving benefit in acute intervention (within 12 hours of onset) in myocardial infarction. This cardioprotective aspect of the drug is likely to be applicable to other areas of ischaemic heart disease, including silent ischaemia.     

Dyslipoproteinaemia in Nigerians with the nephrotic syndrome (an increased risk for ischaemic heart disease?)

Plasma lipids and lipoproteins were measured in 24 Nigerians with the nephrotic syndrome and 29 healthy subjects. None of the patients had been commenced on treatment. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol group (P less than 0.005). By contrast, the HDL-cholesterol to total cholesterol ratio as well as the HDL-cholesterol concentrations were found to be significantly lowered in the nephrotics than the controls (P less than 0.005). A strong correlation was observed between plasma total cholesterol and LDL cholesterol values but not between the other biochemical parameters (r = 0.98.P less than 0.01). These results, though not definitive, suggest that Nigerians with the nephrotic syndrome may represent a risk group for the development of ischaemic heart disease. Long term prospective studies in such patients are desirable to define the effect of these lipid and lipoprotein abnormalities.     

Calcium antagonists in the treatment of hypertension in patients with ischaemic heart disease

Are lives saved or heart attacks prevented by antihypertensive therapy, as a result of blood pressure reduction alone, or because of other properties of the antihypertensive medications which are independent of blood pressure lowering? Long-acting calcium antagonists seem to be as effective as thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors in preventing all-cause mortality and stroke in patients with hypertension, but are probably inferior to ACE inhibitors in preventing coronary artery disease. In patients with symptomatic coronary artery disease, calcium antagonists are generally as effective as β-blockers in relieving angina and improving exercise time-to-onset of angina or ischaemia. Unstable angina or myocardial infarction require treatment with a β-blocker, with an ACE inhibitor added when necessary for blood pressure control or if there is significant left ventricular (LV) dysfunction. If β-blockers are contraindicated and if there is no LV dysfunction, a non-dihydropyridine calcium antagonist can be substituted.     

Calcium antagonists in the treatment of hypertension in patients with ischaemic heart disease

Are lives saved or heart attacks prevented by antihypertensive therapy, as a result of blood pressure reduction alone, or because of other properties of the antihypertensive medications which are independent of blood pressure lowering? Long-acting calcium antagonists seem to be as effective as thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors in preventing all-cause mortality and stroke in patients with hypertension, but are probably inferior to ACE inhibitors in preventing coronary artery disease. In patients with symptomatic coronary artery disease, calcium antagonists are generally as effective as beta-blockers in relieving angina and improving exercise time-to-onset of angina or ischaemia. Unstable angina or myocardial infarction require treatment with a beta-blocker, with an ACE inhibitor added when necessary for blood pressure control or if there is significant left ventricular (LV) dysfunction. If beta-blockers are contraindicated and if there is no LV dysfunction, a non-dihydropyridine calcium antagonist can be substituted.     

New transdermal and transmucosal nitroglycerin delivery systems in patients with ischaemic heart disease

Summary The efficacy of a transdermal (Nitroderm-TTS) and a transmucosal (Trinitrolong) nitroglycerin (NG) formulation has been compared with sublingual NG in 9 patients with ischaemic heart disease and stable angina pectoris. The duration and the degree of anti-ischaemic effect were assessed in terms of similar, individually adjusted work loads performed prior to and repeatedly after drug application in comparison with placebo. The anti-ischaemic effect of nitroderm appeared in 0.5–3 h after administration, reached a maximum in about 3.8 h and persisted for 7.9 h. The maximal nitroderm effect was significantly lower than that of sublingual NG or Trinitrolong. The effect of Trinitrolong was less variable and lasted for 4.6 h. It was evident in all patients 0.5 h after drug administration. Plasma NG levels were monitored in 9 patients after sublingual NG and trinitrolong and in 4 following Nitroderm. The relative bioavailability of Nitroderm and Trinitrolong according to the pharmacokinetic data was 29% and 256%, respectively, of sublingual NG tablets. A therapeutic NG level in blood (0.5 ng/ml) after Trinitrolong appeared much earlier (2 min) than after Nitroderm (1 h). A significant reduction in the effect of sublingual NG was observed during Nitroderm application. Thus, the transdermal NG formulation did not exhibit an antianginal effect lasting for 24 h; transmucosal NG had a relatively short, but more pronounced and stable antianginal effect.