Beneficial effects of diltiazem during myocardial reperfusion: a randomized trial in acute myocardial infarction.
BACKGROUND
Although in experimental models of coronary occlusion diltiazem administration has been shown to reduce the degree of stunning and of reperfusion injury, the majority of clinical trials has failed to demonstrate significant benefits. The aim of this study was to evaluate the effect of diltiazem, administered before coronary reperfusion, on infarct size, residual myocardial viability and recovery of left ventricular function.


METHODS
We studied 90 patients admitted within 3 hours of the onset of symptoms of acute myocardial infarction. They were immediately randomized to either intravenous diltiazem (10 mg bolus + 10 mg/hour for 3 days) (group 1, n = 43) or placebo (group 2, n = 47) and subsequently treated with recombinant tissue-type plasminogen activator. All underwent serial echocardiograms upon admission, 4 days post-admission during low-dose dobutamine stress echo, at discharge and after 6 months. We calculated the dysfunction score (1 = hypokinesia, 2 = akinesia, 3 = dyskinesia) on admission and its percent reduction after dobutamine (viability) and at follow-up (recovery). The 12-lead electrocardiograms were continuously monitored for 3 days and coronary angioplasty was performed whenever the residual stenosis was > 60%.


RESULTS
Upon admission, there were no differences in age, sex, infarct location and size, degree of ST-segment elevation, time from onset of symptoms and dysfunction score. Creatine kinase peaked early in 70% of patients in both groups; the incidences of recurrent ischemia, infarct-related vessel patency and the need for coronary angioplasty were also similar. The creatine kinase peak was significantly higher in group 2 (2931 +/- 2456 vs 1726 +/- 1004 IU/l, p < 0.05). Conversely, in group 1 the residual viability was significantly higher (51 +/- 23 vs 36 +/- 30% improvement in dysfunction score, p < 0.05) and the early recovery of regional function was significantly greater (35 +/- 34 vs 18 +/- 22% at discharge, p < 0.05). On the other hand, the delayed recovery was not significantly different (15 +/- 29 vs 21 +/- 32% from the time of discharge to 6 months of follow-up).


CONCLUSIONS
Intravenous diltiazem, started before coronary reperfusion, has beneficial effects on the infarct size, residual viability and recovery of regional function. If confirmed by larger trials, these preliminary results suggest the use of diltiazem as adjunctive therapy in patients with acute myocardial infarction and undergoing reperfusion.
Pizzetti
G
G
Department of Cardiology and Cardiovascular Sciences, IRCCS Hospital San Raffaele, Milan, Italy. cardiogp@interfree.it
Mailhac
A
A
Li Volsi
L
L
Di Marco
F
F
Lu
C
C
Margonato
A
A
Chierchia
S L
SL
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D017023:Coronary Angiography; D004110:Diltiazem / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D025401:Echocardiography, Stress; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D010960:Plasminogen Activators / Q000627:therapeutic use; D012307:Risk Factors; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects
D002121:Calcium Channel Blockers; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D004110:Diltiazem