A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment of migraine.

OBJECTIVE: This randomized, double-blind, parallel group multicenter study compared response rates and tolerability of zolmitriptan with sumatriptan in the acute treatment of migraine. METHODS: A sample consisting of 1445 outpatients with an established diagnosis of migraine was randomized to zolmitriptan, 2.5 mg or 5 mg, or sumatriptan, 25 mg or 50 mg. Patients took 1 tablet for moderate/severe migraine and a second identical tablet, if necessary, for recurrent headache of moderate/severe intensity 4 to 24 hours after the initial dose. Up to six attacks were treated during a 6-month period. The primary outcome measure was headache response 2 hours after the initial dose. Secondary end points included 1-hour and 4-hour headache response and pain relief over 24 hours. RESULTS: A headache response at 2 hours was noted in 67.1% of patients taking zolmitriptan, 2.5 mg, and 64.8% of those taking zolmitriptan, 5 mg, versus 59.6% of patients taking sumatriptan, 25 mg, and 63.8% of those taking sumatriptan, 50 mg. At 2 and 4 hours, the differences between zolmitriptan, 2.5 mg, and sumatriptan, 25 mg, were statistically significant (odds ratio=1.49 and 1.67, respectively; both P<.001). Statistically significant differences between zolmitriptan, 2.5 mg, and sumatriptan, 50 mg, were seen at 2 and 4 hours post dose (odds ratio=1.21 and 1.23, respectively; both P<.05). At 1 hour post dose, the headache response rate for zolmitriptan, 2. 5 mg, was numerically higher than response rates for sumatriptan, 25 mg and 50mg (odds ratio=1.16, odds ratio=1.06, though they failed to reach statistical significance; P=.061, P=.461 respectively). Differences between zolmitriptan, 5 mg, and sumatriptan, 25 mg, were statistically significant at 1, 2, and 4 hours (odds ratio=1.43, 1. 46, and 1.78, respectively; all P<.001) and at 1 and 4 hours versus sumatriptan, 50 mg (odds ratio=1.28, P=.002; odds ratio=1.29, P=.012, respectively). Although not statistically significant at 2 hours, more patients responded to zolmitriptan, 5 mg, than to sumatriptan, 50 mg (odds ratio=1.16, P=.064). Patients receiving zolmitriptan, 2. 5 mg or 5 mg, achieved more pain relief over 24 hours than patients receiving sumatriptan, 25 mg (odds ratio=1.47, and 1.54 respectively, both P<.001) or sumatriptan, 50 mg (odds ratio=1.17, P=.021; odds ratio=1.22, P=.005, respectively). All treatments were well tolerated. CONCLUSIONS: Zolmitriptan, 2.5 mg and 5 mg, was at least as effective as sumatriptan, 25 mg or 50 mg, for all parameters studied. Zolmitriptan, 2.5 mg, was significantly more effective than sumatriptan, 50 mg, in terms of headache response at 2 and 4 hours. Patients taking zolmitriptan were significantly more likely to have pain relief over 24 hours than those taking sumatriptan.

Effectiveness of three different doses of carvedilol for exertional angina. Carvedilol-Angina Study Group.

Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism. This 4-treatment, 5-period, double-blind, crossover study evaluated the efficacy and safety of 3 doses of carvedilol (12.5, 25, and 50 mg given twice daily) versus placebo in 122 patients with chronic stable angina. Carvedilol in doses of 25 mg twice daily and 50 mg twice daily was statistically superior to placebo with respect to time to angina (placebo: 316 seconds; 25 mg carvedilol: 337 seconds, p = 0.0039; 50 mg: 345 seconds, p <0.0001) and time to 1-mm ST-segment depression (placebo: 301 seconds; 25 mg: 313 seconds; 50 mg: 323 seconds; p <0.0001). The percentage of patients reporting any adverse experience was slightly less in those receiving placebo (placebo: 28.4%; 12.5 mg: 33.1%; 25 mg: 34.5%; 50 mg: 31.9%). Carvedilol is effective and safe in treating patients with chronic stable angina.

Usefulness of nicardipine as monotherapy for chronic, stable angina.

Using a double-blind, Latin square protocol designed to detect dose response, nicardipine hydrochloride, a new calcium antagonist, was studied as monotherapy for stable exertional angina. Eighty-one patients were enrolled in the trial and 62 patients were included in greater than or equal to 1 primary efficacy analyses. Patients received 1 to 2 weeks of placebo run-in, then 5 weeks of treatment with placebo and with 10, 20 and 30 mg of nicardipine given 3 times daily. Patients completed symptom diaries, were monitored with 24-hour electrocardiographic Holter monitors and underwent serial exercise treadmill tests. By 1 hour, 10, 20 and 30 mg of nicardipine administered 3 times daily produced statistically significant, dose-related improvements in all key exercise parameters, which persisted at the 4-hour evaluation. The systolic blood pressure at rest and during exercise decreased, but the pulse slightly increased. The peak rate-pressure product was unchanged. The side effects were not severe. Nicardipine hydrochloride is an effective, well-tolerated medication for the treatment of stable exertional angina, and is a good alternative to currently available calcium antagonists.

Coronary artery disease and ventricular function in angina.

Coronary arteriograms and left ventriculograms of 500 patients with coronary artery disease and angina pectoris were correlated with respect to coronary arterial pattern and left ventricular dyssynergy. We found that the severity of left ventricular dyssynergy was not altered by coronary arterial pattern. The concept of dividing the left ventricle into anterior and posterior zones was validated. Patients with anterior dyssynergy alone or combined anterior and posterior dyssynergy had comparably more severe coronary artery disease in the anterior region than did patients with normal left ventriculograms or posterior dyssynergy alone. Patients with posterior dyssynergy alone or combined anterior anterior and posterior dyssynergy had comparably more severe coronary artery disease in the posterior region than did patients with normal left ventriculograms or anterior dyssynergy alone. Lesions of greater than 90% reduction of coronary arterial luminal diameter best correlated with motion abnormalities of the left ventricular wall.

Semiautomated method for evaluation of left ventricular regional wall motion in coronary artery disease.

Regional left ventricular wall motion was independently assessed in 436 patients using both subjective visual inspection of ventriculograms and objective computer-determined percent change in the square root of the area between systolic and diastolic outlines. Agreement between subjective and objective techniques was greatest at the ventricular apex and least at the base and partly dependent on the number of abnormal segments present. Objective analysis of regional wall motion provides a permanent quantitative record of wall motion and shows good agreement with meticulous subjective inspection of ventriculograms. As such, it has potential as an adjunct to ventriculography.

The treatment of exercise-inducible chronic stable angina with diltiazem. Effect on treadmill exercise.

Although diltiazem has been shown to alleviate vasospastic angina pectoris, its effect on exercise-inducible chronic stable angina has not been objectively studied. Accordingly, the effect of diltiazem was studied in this condition with a placebo controlled double-blind randomized cross-over protocol at three dose levels (120, 180 and 240 mg/day) during graded treadmill exercise. Three end-points were evaluated: 1) time to onset of angina or fatigue if angina were eliminated; 2) time to 1 mm ST segment depression or fatigue if ST depression were eliminated; and 3) time to termination of exercise (2+ angina or fatigue). All end-points were prolonged at all dose levels. At the highest dose of 240 mg/day, time to onset angina or termination was prolonged from a placebo time of 8.0 +/ 0.9 to 9.8 +/- 0.9 minutes (p = < .001); time to ST depression or termination was prolonged from 7.8 +/- 0.9 to 9.1 +/- 0.8 minutes (p = .007); and time to termination was prolonged from 9.9 +/- 0.9 to 10.8 +/- 0.8 minutes (p = .02).

Distribution and severity of coronary artery disease in 500 patients with angina pectoris.

The distribution and severity of coronary disease in 500 patients with angina pectoris and at least one area of 50% or greater reduction of luminal diameter in a major coronary artery were compared with respect to patients' age and coronary arterial pattern. The coronary arterial patterns were separated into right (360 patients), mixed (89 patients), and left (51 patients) systems, depending upon the blood supply to the inferior surface of the left ventricle. The following relationships were noted: 1) In patients with angina pectoris, the distribution and severity of coronary artery disease is similar from the third to eighth decade. 2) Coronary arterial stenoses of 50-70% of greater reduction of luminal diameter involve most frequently the proximal portion of the major vessels. Coronary artery disease is multivessel in nature in 80% of cases. In single vessel disease the left anterior descending artery is involved most frequently. 3) The left main coronary artery is moderately to severely obstructed less frequently in individuals with left (2%) as compared to right (8%) and mixed (10%) systems. Otherwise, the distribution of coronary artery disease is similar in right, mixed, and left systems. 4) Coronary artery disease is a diffuse rather than a focal process. As demonstrated by coronary arteriography, patients with coronary artery disease have smaller vessels throughout the arterial tree as compared with individuals free of evident coronary atherosclerosis.

Combined valvular aortic stenosis, hypertrophic subaortic stenosis and coronary artery disease: successful surgical correction.

A 51 year old woman with angina pectoris due to combined valvular aortic stenosis, hypertrophic subaortic stenosis and coronary artery disease is described. The diagnosis was first suspected following echocardiography. Discussed is the importance of excluding associated coronary artery disease and hypertrophic subaortic stenosis in patients with valvular aortic stenosis. A pre- and post-PVC aortic pressure response is described pathognomonic of coexistent valvular and hypertrophic subaortic stenosis. The patient underwent successful surgical correction of all three lesions.

Use of the air wedge in hemiaxial views of the proximal left coronary artery.

The authors describe a simple, inexpensive method of obtaining hemiaxial views of the proximal left coronary artery, using an inflated air wedge to support the patient at the appropriate angle.