[Effectiveness of various combination therapies in patients with coronary heart disease].
There is only a limited number of studies available comparing the effectiveness of various combinations of anti-ischemic and antianginal substances in the same patients with coronary artery disease and stable angina pectoris and even these are restricted to either only a few drugs or a single point in time for testing. Accordingly, this study was undertaken to determine to what extent the combination of two or three drugs with different anti-ischemic mechanisms of action such as the long-acting form of the beta-blocker metoprolol and isosorbide dinitrate (ISDN) in sustained-release form as well as the calcium channel blockers nisoldipine and diltiazem in sustained-release form, which previously have not been tested in combination, are capable of enhancing effectiveness and prolonging duration of action. In a double-blind, randomized, crossover study in eleven patients with documented coronary artery disease and stable angina pectoris the effects of monotherapy with 200 mg metoprolol in long-acting form were compared with those of combined treatment with 120 mg ISDN sustained-release or 10 mg nisoldipine or 120 mg diltiazem sustained-release as well as ISDN and nisoldipine and finally, ISDN and diltiazem by means of an intraindividual analysis. For assessment of anti-ischemic and antianginal effects, symptom-limited exercise testing was carried out before as well as three, eight, twelve and 24 hours after medication. The parameters analyzed were ST-segment depression at the highest comparable workload, ischemia-free and symptom-free exercise capacity (one minute prior to ST-segment depression of 1 mm or onset of angina pectoris) as well as the systolic blood pressure--heart rate product at the highest comparable workload and at the highest ischemia-free workload, that is one minute prior to an ischemic reaction of 1 mm. Based on the ST-segment depression, all combinations of two drugs (metoprolol and ISDN at three hours; metoprolol and diltiazem at eight hours) led to a significant or at least relative increase of effectiveness. On comparison of the various double combinations, those with nisoldipine showed an early dissipation of action which, twelve hours after administration, was significantly less marked than those with diltiazem. Of the two tested triple combinations, metoprolol, ISDN and diltiazem was either significantly more effective than the various double combinations (metoprolol and ISDN or metoprolol and nisoldipine, both at eight and twelve hours; metoprolol and diltiazem, twelve hours) or relatively more effective and showed clear prolongation of the effects in excess of twelve hours.(ABSTRACT TRUNCATED AT 400 WORDS)
Lehmann
G
G
Deutsches Herzzentrum München.
Reiniger
G
G
Wolf
H
H
Beyerle
A
A
Rudolph
W
W
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004110:Diltiazem / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage; D008790:Metoprolol / Q000008:administration & dosage; D015737:Nisoldipine / Q000008:administration & dosage; D009566:Nitrates / Q000008:administration & dosage*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D009566:Nitrates; D015737:Nisoldipine; D004110:Diltiazem; D008790:Metoprolol; D007548:Isosorbide Dinitrate