Design of a placebo-controlled clinical trial of long-acting diltiazem and aspirin versus aspirin alone in patients receiving thrombolysis with a first acute myocardial infarction. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis (diltiazem) (INTERCEPT) Research Group.

Several pharmacologic forms of adjunctive therapy, designed to enhance the efficacy of thrombolysis following acute myocardial infarction (AMI), are being explored. However, few studies have assessed the use of standard secondary prevention therapies (beta-blockers, angiotensin-converting enzyme inhibitors, magnesium, calcium antagonists, etc.) for antecedent thrombolysis. Although calcium antagonists have not been shown to alter post-AMI mortality, diltiazem has been shown to reduce recurrent nonfatal infarction and myocardial ischemia following non-Q-wave AMI. Because both non-Q-wave AMI and AMI treated with thrombolytic therapy result in early reperfusion and clinical manifestations of "incomplete infarction" (i.e., aborted transmural infarction), we hypothesize that prophylactic administration of diltiazem to AMI patients who receive thrombolysis before other therapies might decrease ischemic complications. We have initiated a multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison of long-acting diltiazem 300 mg/day and aspirin 160 mg/day versus aspirin 160 mg/day alone in up to 920 patients with an uncomplicated first AMI (no heart failure or left ventricular dysfunction) within 36 to 96 hours of receiving thrombolysis. Active enrollment is under way at 46 centers in the United Kingdom, Belgium, The Netherlands, and Denmark. This trial (known as the Incomplete INfarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis [diltiazem], or INTERCEPT) represents the first long-term, large-scale, prospective study of a calcium antagonist administered post-thrombolysis as adjunctive therapy to AMI patients in which the primary trial objective is to assess the effect of blinded therapy on the 6-month cumulative occurrence of a combined clinical end point (cardiac death, recurrent nonfatal AMI, and medically refractory ischemia).

A multicentre study to compare the therapeutic efficacy of sustained-release diltiazem and enalapril in the treatment of patients with mild to moderate hypertension.

A 14-week study was conducted in order to compare the efficacy and tolerability of a twice-daily sustained-release diltiazem preparation (120 or 180 mg) and once-daily enalapril (10 or 20 mg). Patients not achieving an adequate response after 6 weeks on monotherapy were given a combination therapy of twice-daily diltiazem 120 mg and once-daily enalapril 10 mg. Of the 147 patients admitted to the study, 70 received diltiazem and 77 received enalapril; 17 patients subsequently received combination therapy. Blood pressure reductions in patients completing 12 weeks of therapy were (sitting values): diltiazem 120 mg, 10.2/15.2 mmHg; diltiazem 180 mg, 19.1/14.7 mmHg; enalapril 10 mg, 25.7/17.5 mmHg; enalapril 20 mg, 19.6/14.0 mmHg; and combination therapy, 24.6/15.1 mmHg. No significant differences in the incidence level of individual symptoms were seen between the two groups: 34 (49%) in the diltiazem, 37 (48%) in the enalapril group; and, between weeks 6 and 12, 9 (53%) patients taking combination therapy. Two patients withdrew from the enalapril group and 8 from the diltiazem group. No unexpected side-effects were seen during the study and no deaths occurred in any treatment group. Twice-daily sustained-release diltiazem 120 or 180 mg was shown to be an effective antihypertensive agent and equal in efficacy and patient acceptability to once-daily enalapril 10 or 20 mg. Combination therapy effectively lowered blood pressure in patients in whom monotherapy was ineffective.

A comparative study of long acting diltiazem (Tildiem LA) with sustained release nifedipine (nifedipine SR) and bendrofluazide in the treatment of mild to moderate hypertension.

The therapeutic efficacy of long acting diltiazem 300 mg od (Tildiem LA) was compared with sustained release nifedipine 20 mg bd and bendrofluazide 5 mg od in a multicentre study with 230 patients diagnosed with mild to moderate essential hypertension, with 77, 77 and 76 randomized to the diltiazem, nifedipine SR and bendrofluazide groups respectively. Patients were entered into this randomised, single (investigator) blind, parallel-group multicentre study if the systolic and diastolic blood pressures were > or = 145 mm Hg and/or 95 mm Hg respectively at the admission visit. Twenty-one general practitioners and two hospital physicians monitored patients at baseline and at four and eight weeks of continuous dosing. After eight weeks of therapy, clinically acceptable control of blood pressure was seen in all groups: reductions were 19.2/13.5 mm Hg, 20.4/14 mm Hg and 18.5/10.8 mm Hg for the Tildiem, nifedipine and bendrofluazide groups respectively. Significant differences were shown between bendrofluazide and the other two groups on diastolic pressures (p = 0.01). The non-significant trend was for systolic pressures to mirror these effects. Significantly higher withdrawals caused by adverse events were seen with nifedipine. These were as follows: 14 patients receiving nifedipine (18%), 5 patients receiving diltiazem (6%) and 4 patients receiving bendrofluazide (5%). The difference in this withdrawal rate between treatments was statistically significant (p = 0.01). Post hoc tests revealed that both diltiazem and bendrofluazide had statistically significant lower withdrawals for adverse events than the nifedipine group (p = 0.047). Nifedipine was associated with a marginal increase in standing apex pulse rate and only diltiazem LA significantly maintained serum potassium levels. These results indicate that diltiazem 300 mg is an effective antihypertensive agent and is equivalent in efficacy to nifedipine SR 20 mg and both are superior to bendrofluazide. Nifedipine SR was however the worst tolerated and had the highest withdrawal rate (p = 0.013).