Increased exercise tolerance and reduced electrocardiographic ischemia with diltiazem in patients with stable angina pectoris.

Wagniart, P; Ferguson, R. James; Chaitman, Bernard R.; Achard, F; Benacerraf, A; Delanguenhagen, B; Morin, B.; Pasternac, A; Bourassa, Martial G.

doi:10.1161/01.cir.66.1.23

Cited by 63 publications

(8 citation statements)

References 23 publications

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“…On propranolol alone the mean plasma propranolol concentration was 118 ng/ml (range 64 to 183) and in combination with diltiazem it was 109 ng/ml (range 23 to 180 THERAPY AND PREVENTION-CORONARY ARTERY DISEASE ment in exercise capacity with an increase in dose levels from 120 mg to 240 mg/day. Single-dose studies in which as much as 120 mg diltiazem was used15 16 have shown no associated significant adverse effects. Consequently, we wanted to examine the short-term safety and efficacy of high-dose diltiazem (90 mg four times daily) in patients with stable effort angina.…”

Section: Resultsmentioning

confidence: 99%

The effect of diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: a double-blind, randomized, and placebo-controlled study.

Hung¹,

Lamb²,

Connolly³

et al. 1983

Circulation

152

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The effects of oral diltiazem and propranolol, alone and in combination, were compared with those of placebo in 12 patients with stable effort angina. Patients performed symptom-limited, multistage, upright bicycle ergometric exercise while undergoing equilibrium-gated radionuclide angiographic examination after 2 week periods of 90 mg diltiazem four times daily, 60 mg propranolol four times daily, a combination of 90 mg diltiazem and 60 mg propranolol four times daily, and placebo. All drugs were given double blind and in randomized order. Diltiazem, propranolol, and the combination significantly increased exercise duration compared with placebo (562 + 149, 525 + 115, and 549 121, vs 430 + 132 sec); the drugs also increased time to onset of angina pectoris and ischemic ( 1 mm) ST segment depression (all p < .05). Compared with after placebo, heart rate and rate-pressure product at a fixed submaximal workload were decreased after diltiazem (both p < .05), but were unchanged at peak effort. Heart rate and rate-pressure product at both submaximal and peak effort were decreased by propranolol (all p < .001) and were decreased further by the combination of diltiazem and propranolol (all p < .05 vs propranolol). Diltiazem and the combination of diltiazem and propranolol decreased maximal exercise ST segment depression (both p < .01 vs placebo). The mean exercise left ventricular ejection fraction was higher in patients on diltiazem than in those on placebo, propranolol, or the combination of diltiazem and propranolol (all p < .05). Adverse side effects severe enough to require dosage reduction (severe sinus bradycardia or orthostatic hypotension) occurred in four patients on combination therapy. High-dose diltiazem alone appears to be as effective as or more effective than moderate-dose propranolol or the combination of diltiazem and propranolol in improving exercise tolerance, myocardial ischemia, and left ventricular function in patients with stable effort angina.Circulation 68, No. 3, 560-567, 1983. CALCIUM-CHANNEL BLOCKERS provide a promising alternative to /8-blockers for the management of patients with exertional angina and fixed coronary artery disease. These drugs can reduce myocardial oxygen demand by decreasing systemic vascular resistance, and in some cases cardiac contractility and heart rate, while producing an increase in coronary blood flow through dilation of large coronary vessels. 1

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Section: Resultsmentioning

confidence: 99%

The effect of diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: a double-blind, randomized, and placebo-controlled study.

Hung¹,

Lamb²,

Connolly³

et al. 1983

Circulation

152

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show abstract

“…Although calcium antagonists are now universally only in chemical structure but also in terms of recognized as major therapeutic agents in their negative inotropic effects or their effects on ischaemic heart disease (Hugenholtz et al, 1981; myocardial relaxation, coronary blood flow, and Gunther et al, 1981;Zacca et al, 1982;Rouleau oxygen consumption (Rousseau et al, 1980(Rousseau et al, , et al, 1983Wagniart et al, 1982;Braunwald, 1981;Walsh & O'Rourke, 1983;Gelpi et al, 1983), the pharmacologic profile of the ideal 1983; Rouleau et al, 1983; Emanuelsson & calcium antagonist to treat angina pectoris Holmberg, 1983;Krebs, 1984). remains ill defined.…”

Section: Introductionmentioning

confidence: 99%

Effects of nicardipine on coronary blood flow, left ventricular inotropic state and myocardial metabolism in patients with angina pectoris.

Rousseau¹,

Vincent²,

Cheron³

et al. 1985

Brit J Clinical Pharma

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1 The effects ofintravenous nicardipine (2.5 mg) on the left ventricular (LV) inotropic state, LV metabolism, and coronary haemodynamics were analysed in 22 patients with angina pectoris. 2 Measurements were made at fixed heart rate (atrial pacing), under basal state, and during a cold pressor test. 3 After nicardipine, coronary blood flow and oxygen content in the coronary sinus increased significantly. 4 The indices of inotropic state increased slightly, and the rate of isovolumic LV pressure fall improved. 5 Myocardial oxygen consumption was unchanged despite the significant reduction in pressure-rate product, but LV lactate uptake increased, particularly during the cold pressor test. 6 When nicardipine was administered after propranolol, the indices of inotropic state were unaffected. 7 The lack of direct effect of nicardipine on LV inotropic state was further confirmed by intracoronary injection of 0.1 and 0.2 mg in a separate group of 10 patients. 8 It is concluded that the nicardipine-induced coronary dilatation seems to improve perfusion and aerobic metabolism in areas with chronic ischaemia, resulting in reduced lactate production and augmented oxygen consumption. Keywords angina pectoris coronary vascular resistance inotropic state myocardial metabolism nicardipine vasodilatation

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“…Dose titration studies have shown that beneficial effects of diltiazem can be demonstrated by exercise treadmill testing in patients with coronary artery disease at doses of 240 mg/day, but not at lower doses. "7 Single doses of 90 to 120 mg have also been demonstrated to be effective.8 9 Little data exist concerning the effects of higher doses of diltiazem (360 mg/day) on resting hemodynamics and left ventricular performance during exercise. Therefore, the purpose of this study was to evaluate the safety, efficacy, and hemodynamic effects of 360 mg/day diltiazem in divided doses for the treatment of chronic stable exertional angina pectoris.…”

mentioning

confidence: 99%

Short- and long-term efficacy of high-dose oral diltiazem for angina due to coronary artery disease: a placebo-controlled, randomized, double-blind crossover study.

Petru¹,

Crawford²,

Sorensen³

et al. 1983

Circulation

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The effects of oral diltiazem (360 mg/day) on exercise tolerance, left ventricular performance, and plasma lactate and catecholamine levels were studied in 13 patients with atherosclerotic coronary artery disease in a placebo-controlled, randomized, double-blind protocol. Exercise duration to the onset of ischemic ST segment depression, time to angina pectoris, and time to peak exercise improved by 120, 174, and 144 sec, respectively (p < .0001). Left ventricular ejection fraction, as determined by radionuclide angiography, increased in patients at rest from 52 + 11% (mean + SD) during placebo therapy to 58 11% during diltiazem therapy (p < .001); at peak exercise ejection fraction increased from 44 11% during placebo treatment to 52 + 15% during diltiazem therapy (p < .01). The mean plasma norepinephrine level in patients at rest increased from 498 + 221 pg/ml during placebo treatment to 667 + 272 pg/ml during diltiazem therapy (p < .05).Resting standing blood pressure and supine and standing diastolic blood pressures decreased significantly with diltiazem. In all 10 patients followed over a long term, oral diltiazem caused persistent improvement in exercise performance at 12 to 20 weeks, without evidence of placebo effects. Thus, diltiazem is highly effective in divided doses of 360 mg/day for the therapy of chronic angina pectoris due to coronary artery disease.Circulation 68, No. 1, 139-147, 1983. DILTIAZEM HYDROCHLORIDE has been shown to be effective in the treatment of exertional angina pectoris in doses of 240 mg/day.

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Increased exercise tolerance and reduced electrocardiographic ischemia with diltiazem in patients with stable angina pectoris.

Cited by 63 publications

References 23 publications

The effect of diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: a double-blind, randomized, and placebo-controlled study.

The effect of diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: a double-blind, randomized, and placebo-controlled study.

Effects of nicardipine on coronary blood flow, left ventricular inotropic state and myocardial metabolism in patients with angina pectoris.

Short- and long-term efficacy of high-dose oral diltiazem for angina due to coronary artery disease: a placebo-controlled, randomized, double-blind crossover study.

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