19th Congress of the European Society of Cardiology

Diltiazem the Drug of Choice for Patients with Non-Q Wave Myocardial Infarction


STOCKHOLM, SWEDEN -- Diltiazem should be considered the first line therapy for patients with non-Q wave myocardial infarction, according to Dr. Robert Roberts, professor of cell biology, and chief of cardiology at Baylor University College of Medicine in Houston,
Texas.

Dr. Roberts presented his findings at the 19th Congress of the European Society of Cardiology, held in Stockholm, Sweden, recently. He said the current revolution in cardiology has emphasized thrombolytic therapy for patients who present to the hospital emergency room with bundle branch block or ST segment elevation. However, more than half of patients with acute infarction do not show these findings on electrocadiograms, and therefore, do not benefit from thrombolytic therapy.

Dr. Roberts discussed a number of studies which either support the use of diltiazem, or question some aspects of using other drugs in patients with non-Q-wave infarction.

The ISIS II (International Study of Infarct Survival) and GISSI (Italian Study Group for Streptokinase in Myocardial Infarction) looked at more than 28,000 patients in total, and failed to show any benefit for thrombolytic therapy among the small number of patients who had ST segment depression or T-wave inversion.

GISSI-III looked at 18,895 patients and found that among the 18 percent who had non-Q wave infarction, there were no significant differences in outcomes between those taking nitrates and those taking the ACE inhibitor lisinopril.

However, the TIMI IIIb (Thrombolysis in Myocardial Infarction, Phase IIIb) trial was specifically designed to answer the question of how patients with ST segment depression or T-wave inversion would respond to a conventional therapy including diltiazem, heparin and beta blockers, plus tPA versus aggressive therapy which included cardiac catheterization and angioplasty. The results showed no difference between the placebo group and the group receiving tPA.

In a group with unstable angina who received tPA -- approximately two-thirds of the patients -- there was an increased incidence of infarction. Furthermore, the incidence of infarction and death increased in the tPA group, necessitating a premature end to the trial.

This clearly shows the thrombolytic therapy is not beneficial, and might even have a deleterious effect in patients presenting with ST segment depression, Dr. Roberts said.

"Overall, our recommendation was that thrombolytic therapy was not indicated routinely in patients with ST segment depression," he said.

And while it’s true that the risk of Q-wave infarction is greater among patients with ST elevation than among those with ST segment depression, far more patients present in hospital ERs with ST segment depression. Again this suggests a sizable population who should not be treated with thrombolytic therapy.

As for beta blockers, there are no data, prospective or otherwise, in which there were adequate numbers of patients with non-Q wave infarction treated with beta blockers. The only study with a large enough patient population to be meaningful was the so-called MIAMI (Metoprolol in Acute Myocardial Infarction) trial which looked at 5,000 patients, 1,100 of whom had non-Q wave infarction. In that study, metoprolol was associated with a 50 percent increase in mortality among those in the non-Q-wave group.

Dr. Roberts said the relatively small size of the non-Q-wave group could make the data less than conclusive, but nonetheless, his "inkling" based on those numbers was that metoprolol was not beneficial.

Similarly, a retrospective analysis of the BHAT (Beta Blocker and Heart Attack Trial) showed no benefit from beta blockers in treating ST segment depression, but the numbers were too small to draw any conclusion.

In 1986, researchers at Baylor did a study of 576 patients with non-Q wave infarctions to determine whether they could decrease the incidence of re-infarction, which is a common occurrence in this group. The results showed that diltiazem reduced the incidence of re-infarction from 13 percent to 6 percent (diltiazem vs placebo), and refractory angina, 6 percent versus 3.5 percent.

The MDPIT (Multi-Center Diltiazem Post-Infarction Trial) conducted in Canada and the United States dealt with both Q-wave and non Q-wave infarctions but found just one very important difference: of the patients who presented with heart failure and were treated with diltiazem, 20 percent died.

"This was the first clinical trial to show that diltiazem, or any calcium channel blocker, was deleterious in patients who already had cardiac failure," said Dr. Roberts. In the remaining 80 percent, there was a 27 percent benefit in the patients who were treated with diltiazem, with the majority of this benefit being observed in the non-Q wave group. In fact, 29 percent of them had non-Q wave infarction and at the end of the first year, there was a 40 percent reduction in death and infarction. This benefit was carried out to 4.5 years among more than 600 patients with non-Q wave infarction, showing a 34 percent reduction in death and infarction overall among the diltiazem group.

In effect, the only benefit shown was among the non-Q wave patients who were treated with diltiazem, Dr. Roberts said.

"The benefit you see in the 80 percent of patients without heart failure was primarily benefit in non-Q wave patients in preventing death and re-infarct in that group."

Even the DAVIT I and II trials, which looked at the calcium channel blocker verapamil, failed to show a significant reduction in mortality although the number of patients involved was small. However, when the results of the DAVIT trials and the MDPIT were subjected to meta-analysis, involving more than 5,677 patients followed for 550 days, cardiac mortality was significantly decreased among those patients with non-Q-wave infarctions who took diltiazem.

Finally, the recently released VANQUISH study found that among more than 900 patients with non-Q wave infarction, those who were managed conservatively with drugs had lower rates of death and re-infarction than those who were managed aggressively with angioplasty and cardiac catheterization. These figures were statistically significant at one month, but lost their significance at one year.

In the VANQUISH trial, only 35 percent of the patients received diltiazem, with the rest receiving either beta blockers or another calcium channel blockers, yet those treated with diltiazem experienced fewer cardiac events than those treated with any other drug, including the beta blockers or the other calcium channel blockers.