The calcium channel blockers verapamil and diltiazem can be considered together because their net pharmacologic effect is that of slowing the heart rate and, in some instances, reducing myocardial contractility (36), thereby reducing myocardial oxygen demand. These studies are closer to more conventional secondary prevention design, since patients in these studies were treated with the active agent after their index MI was stabilized. A recent pooled analysis by Yusuf and colleagues (43) indicated that verapamil and diltiazem had no effect on mortality following AMI, but that they exerted a significant effect on reducing the rate of reinfarction (6.0 vs 7.5%; odds ratio 0.79; 95% CI: 0.67-0.94; p < 0.01) (Table 4). The effect seems similar for both agents.
Although the overall results of trials with verapamil showed no mortality benefits, subgroup analysis showed that immediate-release verapamil initiated several d after AMI in patients who were not candidates for a b-blocking agent may be useful in reducing the incidence of the composite end point of reinfarction and death, provided LV function is well preserved with no clinical evidence of heart failure. In a placebo-controlled trial of almost 1800 patients, verapamil 360 mg/d started in the second wk after AMI and continued for a mean of 16 mo had no effect on mortality compared to the control group, but reduced major event rates (death or reinfarction) from 21.6% in the control group to 18.0% in the active treatment group (p = 0.03) (46). In patients without heart failure in the coronary care unit, however, verapamil significantly reduced both mortality (from 11.8% in the control group to 7.7% in the active treatment group; p = 0.02) and major events (from 19.7% in the control group to 14.6% in the active treatment group; p = 0.01), but there was no effect on either end point among patients who experienced CHF in the coronary care unit (46). Verapamil is detrimental to patients with heart failure or bradyarrhythmias during the first 24-48 h after AMI (15,47,48).
Data from the Multicenter Diltiazem Postinfarction Trial (MDPIT) and the Diltiazem Reinfarction Study (DRS) (49,50) suggest that patients with non-Q wave MI or those with Q wave infarction, preserved LV function, and no evidence of heart failure may also benefit from treatment with immediate-release diltiazem. In the DRS, 576 patients with non-Q wave MI were treated with either diltiazem (90 mg every 6 h) or placebo initiated 24-72 h after the onset of MI and continued for 14 d (50). There was no difference in mortality, but diltiazem reduced the rate of reinfarction from 9.3% in the control group to 5.2% (p < 0.03) and the rate of refractory postinfarction angina from 6.9% in the control group to 3.5% (p = 0.03). In the MDPIT, 2466 patients with a Q wave or non-Q wave MI were treated with either diltiazem (240 mg/d) or placebo 3-15 d after the MI onset and followed for a mean of 25 mo. There was no difference in mortality in the two treatment groups (49). A significant bidirectional interaction was observed, however, between diltiazem and the presence of pulmonary congestion during the index MI (Fig. 6). In the 1909 patients without pulmonary congestion, diltiazem was associated with a significant reduction in cardiac events at 1 yr from 11% in the control group to 8%, whereas in the 490 patients with pulmonary congestion, diltiazem increased the cardiac event rate from 18% in the control group to 26%. A similar pattern was observed with respect to the ejection fraction, which was dichotomized at 40% (49). The results of MDPIT may be confounded by the fact that 53 and 55% of placebo- and diltiazem-treated patients, respectively, received concomitant P-blocker therapy. Also, both the MDPIT and DRS projects were conducted in an era when the use of aspirin was not as prevalent as it is today, raising further uncertainty about the relevance of their findings for contemporary management of AMI (15). Of particular clinical importance is the detrimental mortality effect of diltiazem in patients with LV dysfunction.
It should be emphasized that there have not been studies comparing the efficacy of verapamil or diltiazem with that of a P-blocker. P-Blockers more consistently reduce both mortality and reinfarction and should be recommended for those patients who can tolerate such medication. Verapamil or diltiazem may be a reasonable alternative for those patients who cannot tolerate a P-blocker, but who can tolerate one of the calcium blockers, for example, patients with severe chronic obstructive pulmonary disease or asthma. It should be noted, however, that many patients who cannot tolerate a P-blocker, because of concern of excessive bradycardia or CHF, may experience similar complications from diltiazem or verapamil.
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