Randomized, double-blind comparison of propranolol alone and a propranolol-verapamil combination in patients with severe angina of effort

Winniford, Michael D.; Huxley, Robert; Hillis, L.David

doi:10.1016/s0735-1097(83)80078-3

Cited by 41 publications

(9 citation statements)

References 36 publications

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“…Monitoring blood pressure during commencement of treatment in patients with coronary artery disease would be advisable. The incidence of adverse effects during active treatment was common, but reported effects were minor and were similar in frequency and severity to those reported during placebo treatment and to previous studies with calcium entry blockers (Dawson et al, 1981), P-adrenoceptor blockers (Winniford et al, 1983;McNeil et al, 1979) and a-adrenoceptor blockers (Collins & Sheridan, 1985).…”

Section: Introduction Methodssupporting

confidence: 72%

Effects of felodipine on haemodynamics and exercise capacity in patients with angina pectoris.

Sheridan¹,

Thomas²,

Routledge³

et al. 1987

Brit J Clinical Pharma

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1 We studied the effects of adding felodipine to W3-adrenoceptor blockade on haemodynamics and exercise capacity in 14 patients with stable angina pectoris using a placebo controlled double-blind crossover protocol. 2 Felodipine reduced supine and standing systolic pressure by 13% (P < 0.01) and 14% (P < 0.01) respectively and increased supine heart rate 7.4% (P < 0.05). 3 Felodipine at a plasma concentration of 15.5 ± 3.0 nmol 1-1 increased exercise duration by 16% (P < 0.01) but failed to attenuate the degree of ST segment depression during exercise. 4 The mean daily number of episodes of angina (0.53 ± 0.16 on placebo vs 0.37 ± 0.11 on felodipine) and mean daily GTN consumption (0.51 ± 0.07 on placebo vs 0.36 ± 0.12 on felodipine) were not significantly reduced (0.1 < P > 0.05). 5 These findings suggest that felodipine may provide useful additional benefits in patients with hypertension or angina pectoris, who are already receiving ,3-adrenoceptor blockers.

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Section: Introduction Methodssupporting

confidence: 72%

Effects of felodipine on haemodynamics and exercise capacity in patients with angina pectoris.

Sheridan¹,

Thomas²,

Routledge³

et al. 1987

Brit J Clinical Pharma

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“…Treatment of angina pectoris with 8-adrenoceptor antagonists and verapamil in combination is effective and increasingly common (Lessem, 1983;Winniford et al, 1983). Furthermore, it has recently been suggested that verapamil and other calcium antagonists may be useful in the treatment of older patients with hypertension (Buhler et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of verapamil in combination with atenolol, metoprolol and propranolol.

Warrington¹,

Holt²,

Johnston³

et al. 1984

Brit J Clinical Pharma

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Treatment of angina pectoris with beta‐adrenoceptor antagonists and verapamil in combination is effective and increasingly common. The study reported here was designed to show whether the pharmacokinetics of verapamil are influenced by concurrent treatment with three different beta‐adrenoceptor blockers, and whether there is any pharmacodynamic interaction between these drugs. Twelve healthy volunteers (eight men, four women) aged 21‐25 years and weighing 48‐82 kg consented to participate in the study. They received verapamil 50 mg three times daily for four 1‐week periods, each separated by a 1 week ‘washout’ period. During three of the four treatment periods, the subjects took either atenolol 100 mg once daily, metoprolol 100 mg twice daily or propranolol 80 mg twice daily; in the remaining period they took verapamil alone. The concentration/time curve and plasma elimination half‐life of verapamil and norverapamil, its major metabolite, were not influenced by 1 weeks co‐administration atenolol, metoprolol or propranolol. As expected, co‐administration of each of the beta‐adrenoceptor blockers significantly reduced exercise heart rate when compared with verapamil alone.

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“…* Combination therapy of a beta blocker with verapamil is associated with a relatively high risk of serious adverse effects even i n those who tolerate either drug alone. 9 In some patients the hypotensive effects of nifedipine, exacerbated by beta blockade, may become severe enough to aggravate angina.'" Diltiazem appears to be associated with fewer overall side effects when used alone or in combination with beta blockers.II It may therefore be preferred to verapamil or nifedepine in those requiring combination therapy.…”

Section: Discussionmentioning

confidence: 99%

Electrophysiologic effects of oral diltiazem before and after beta blockade

Kumar

Bajaj

Kaul

et al. 1991

Clinical Cardiology

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Summary:We conducted electrophysiologic (EP) studies and cstirnated the sinus nodc function and atrioventricular ( A V ) conduction in 10 patients with suspected coronary arterial disease (age range 35-55 years) before and during diltiazem therapy (60 mg thrice daily for 5-7 days). The effect of beta blockade (0.1 mg/kg of intravenous propranolol) was evaluated in both EP studies. The mean spontaneous sinus cycle length (SCL) and the AV nodal Wenckebach cycle lengths (AVWB) were significantly higher (p < 0.05) after propranolol alone (9 I3 f 13 1 and 504 197 ms, respectively) compared with baseline values (SCL: 827f 149 ms, AVWB: 439f 173 ms). Diltiazem alone failed to influence the SCL and AVWB significantly. Nonc of the other parameters (sinoatrial conduction time, corrected sinus node recovery time, AH and HV intervals, AV nodal and atrial effective refractory periods) were significantly influenced by propranolol, diltiazem, or the combination. No patient developed AV block, sinus arrest/sinoatrial exit block, or symptomatic sinus brddycardia following beta blockade after diltiazem administration. Oral diltiiizeni therapy alone and after beta blockade does not appear to adversely influence the sinus node function and AV conduction in patients below the age of 55 years. The combination of diltiazem and beta blocker thus appears safe in selected patients with coronary arterial disease.

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Randomized, double-blind comparison of propranolol alone and a propranolol-verapamil combination in patients with severe angina of effort

Cited by 41 publications

References 36 publications

Effects of felodipine on haemodynamics and exercise capacity in patients with angina pectoris.

Effects of felodipine on haemodynamics and exercise capacity in patients with angina pectoris.

Pharmacokinetics and pharmacodynamics of verapamil in combination with atenolol, metoprolol and propranolol.

Electrophysiologic effects of oral diltiazem before and after beta blockade

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