Skip to main content
SpringerLink
Log in

Verapamil

A Review of its Pharmacological Properties and Therapeutic Use in Coronary Artery Disease

  • Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Synopsis

Verapamil has well proven efficacy in the treatment of patients with hypertension, and early studies indicated its efficacy in the treatment of coronary artery disease. The. efficacy of verapamil relative to placebo in patients with stable angina pectoris is confirmed, and the drug is at least as effective as nifedipine, propranolol or metoprolol and of similar efficacy to bepridil and nicardipine when administered as a conventional or sustained release formulation.

Verapamil is the first calcium antagonist to be shown in a double-blind study to significantly reduce mortality and reinfarction rate after acute myocardial infarction inpatients without heart failure. In these patients, the reduction in mortality achieved with verapamil was similar to that reported with β-adrenoceptor antagonists, suggesting that verapamil may be a suitable alternative to β-blockers as secondary prevention in patients intolerant of these drugs.

Recurrence of stenosis in patients who successfully undergo percutaneous transluminal coronary angioplasty (PTCA) limits the usefulness of the procedure. Verapamil has recently been shown to significantly reduce the rate of restenosis in patients with stable angina at risk of recurrence, although these initial results require confirmation.

Verapamil, therefore, is effective in the treatment of patients with stable angina pectoris, appears to be an alternative to β-blockers in selected patients as late start secondary prevention after acute myocardial infarction and has a potential role in preventing recurrent stenosis after PTCA, if initial results are confirmed.

Pharmacodynamic properties

Single intravenous doses of verapamil lower blood pressure, increase heart rate, decrease systemic vascular resistance and increase cardiac output in patients with coronary artery disease. However, during 4 weeks’ treatment with verapamil 360mg daily blood pressure is decreased by only about 10% in patients without hypertension, and cardiac output, resting and exercise heart rate are unaffected. Assessment of the effects of oral verapamil on left ventricular function using doppler echocardiographic techniques revealed changes indicative of improved early filling and enhanced relaxation, although studies employing both invasive and noninvasive techniques reported a variable effect of intravenous verapamil on diastolic function. Generally however, the negative inotropic effect of verapamil is counterbalanced by its vasodilatory effect and consequent reduction in afterload. When administered intravenously, verapamil decreased coronary vascular resistance without altering myocardial oxygen consumption, or vice versa, in patients with coronary disease. The effect of verapamil on double product has also varied, with results ranging from significant to non-significant reductions.

Experimental studies have shown that calcium overload of the arterial wall is important to the pathogenesis of atherosclerotic lesions. Additionally, by inhibiting the transport of calcium into myocardial cells, calcium antagonists may protect against myocardial necrosis. Verapamil has been shown to decrease infarct size in animal models and to decrease the release of the cardiac-specific isoenzyme of creatine kinase (CK-MB) and infarct size when administered to patients prior to aortic cross clamping or within a few hours of acute myocardial infarction. Verapamil also improved the ischaemic tolerance of the poststenotic myocardium in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Regional blood flow was improved by verapamil in the postischaemic ‘stunned’ myocardium model.

In patients with coronary artery disease, verapamil decreased plasma norepinephrine (noradrenaline) levels without altering levels of epinephrine. Blood flow reduction caused by exogenous epinephrine at the site of stenosis in dogs was inhibited by verapamil, as was the generation of platelet derived thromboxane B2. In vitro, platelet aggregation induced by adenosine diphosphate was inhibited by concentrations of verapamil equivalent to therapeutic plasma concentrations. Blood from patients treated with sustained release verapamil 240mg daily for 7 days significantly inhibited thrombus formation on porcine aortic media. Verapamil, like other calcium antagonists, has demonstrated antiatherosclerotic activity in studies conducted in animals.

Pharmacokinetic Properties

Verapamil undergoes extensive first-pass hepatic metabolism resulting in systemic availability of 10 to 20%. Peak plasma concentrations (Cmax) and bioavailability of verapamil and its active metabolite norverapamil are substantially higher after repeated administration than after a single dose and vary among patients. Cmax values are decreased by food, an effect which is more marked when verapamil is administered immediately after, rather than with, a meal. The effect of food was more marked with conventional than sustained release formulations. The bioavailability of a once-daily sustained release formulation is similar to that of a conventional formulation administered 3 times daily.

Verapamil is widely distributed throughout the body with an apparent volume of distribution of 257 to 406L following oral administration to healthy volunteers. Protein binding of verapamil and norverapamil is about 92 and 97 %, respectively, in patients treated long term with verapamil 240 to 480mg daily. Verapamil is extensively metabolised in the liver and over a period of 5 days 70% is excreted in the urine and 15% in the faeces, with only 3% recovered unchanged in the urine of volunteers. In patients with angina pectoris, the mean elimination half-life (t1/2β) is 3.6 hours after a single dose and 7.9 hours during long term administration of a conventional formulation. In comparison, the t1/2β of a sustained release formulation was between 5.3 and 9.6 hours after administration of a single dose to healthy volunteers.

Total body clearance and volume of distribution are decreased and t1/2β increased in the elderly compared with in young volunteers. Systemic clearances are reduced 2- to 5-fold and t1/2β values increased about 5-fold in patients with cirrhosis. Pharmacokinetic properties of verapamil are not usually altered in patients with impaired renal function.

Therapeutic Efficacy

In the treatment of patients with stable angina pectoris, verapamil, administered as a conventional or sustained release formulation, produced a greater increase in exercise duration and time to ST-segment depression and a greater decrease in the extent of ST-segment depression, attack frequency and nitroglycerin (glyceryl trinitrate) consumption than placebo. Under double-blind crossover conditions, verapamil 360mg daily was at least as effective as nicardipine 90mg daily in improving objective and subjective criteria and in reducing the mean number of ischaemic episodes during ambulatory monitoring. Administered as a conventional or sustained release formulation, verapamil 360mg daily was generally more effective than nifedipine 60mg daily. Sustained release verapamil 480mg daily reduced the number of ischaemic episodes in 24 hours similarly to a combination of nifedipine 40mg and propranolol 260mg daily. Relatively low doses of verapamil and bepridil were of similar efficacy whereas bepridil 300 to 450mg daily tended to be more effective than verapamil 240 to 360mg daily in improving exercise duration.

Patients with persistent angina in spite of treatment with the maximum tolerated dose of propranolol had improved exercise tolerance when verapamil was added. The combination of verapamil and a β-blocker was invariably more effective than either drug alone in increasing exercise tolerance. Verapamil 240mg and bisoprolol 10mg daily and verapamil 360mg and bisoprolol 20mg daily were similarly effective in reducing attack frequency in patients with ‘mixed angina’.

Sustained release verapamil 120mg and the same dosage of isosorbide dinitrate were of similar efficacy but the efficacy of verapamil was sustained over the 2-week study period whereas that of the nitrate declined. The antianginal efficacy of equal daily dosages of sustained release and conventional formulations of verapamil was similar. The efficacy of verapamil reported after 2 to 8 weeks’ treatment was maintained over 12 months in noncomparative trials.

Verapamil 360 to 480mg daily was more effective than propranolol 120 to 300mg in improving symptoms and reducing symptomatic and asymptomatic ischaemic events in patients with unstable angina. Similar efficacy was provided by verapamil and metoprolol, and verapamil and nifedipine, whether administered as conventional or sustained release formulations.

The efficacy of verapamil as secondary prevention after acute myocardial infarction has been assessed in 2 relatively large trials [Danish Verapamil Infarction Trials I and II (DAVIT I and II)]. In the first of these trials, verapamil administered intravenously immediately after admission to the coronary care unit and orally thereafter for 6 months failed to reduce mortality compared with placebo. However, retrospective analyses indicated that verapamil reduced mortality between days 22 and 180 and prompted a second trial in which oral verapamil was started in the second week after admission. Intention-to-treat analysis of results from DAVIT II revealed that treatment with verapamil significantly reduced the incidence of first major events (death or reinfarction), first reinfarctions and first cardiac event. Total mortality at 18 months was not significantly reduced by verapamil, but was significantly reduced in patients without heart failure immediately before randomisation. Late intervention with verapamil treatment did not worsen symptoms in patients with heart failure. To date, verapamil is the only calcium antagonist which has been shown to significantly decrease mortality and reinfarction rate in patients with confirmed myocardial infarction.

Results of a study designed to determine if long term treatment with verapamil or metoprolol improves prognosis in patients with stable angina pectoris indicated that incapacitating angina pectoris, myocardial infarction or a cerebrovascular incident occurred with similar frequency in patients treated with either drug.

In patients at risk of restenosis after PTCA, administration of verapamil 240mg twice daily for 6 months significantly reduced the rate of restenosis compared with placebo among compliant patients. Verapamil was effective in patients with stable angina but not in those with unstable angina or non-Q wave infarction. All patients received aspirin and dipyridamole in addition to the study regimen.

Tolerability

As reported in an earlier review in Drugs, constipation, the most common adverse event, occurred in 5% of patients and necessitated treatment withdrawal in 1.4%. Headache was reported in 1.1 % and dizziness, rash, ankle oedema, dyspepsia and lethargy were reported in fewer than 1 % of patients. Adverse event data in patients with angina pectoris treated with verapamil are available only from clinical trials, but in a recent long term comparison with metoprolol in patients with stable angina both drugs were similarly tolerated. Conduction disturbances occurred in a widely varying proportion of patients with coronary artery disease treated with verapamil, although these were usually asymptomatic.

Dosage and Administration

The usual oral dosage of verapamil in patients with stable or unstable angina is 240mg daily administered as a conventional formulation in divided doses or a sustained release formulation once daily. Dosage should be titrated to the optimum for each patient. If verapamil is administered concomitantly with a β-blocker, patients should be monitored for bradycardia and conduction disturbances, particularly after dosage increments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Silke B, Verma SP, Nelson GI, et al. The effects on left ventricular performance of verapamil and metoprolol singly and together in exercise-induced angina pectoris. Am Heart J 1985 Jun; 109: 1286–93

    PubMed  CAS  Google Scholar 

  2. Klein HO, Ninio R, Oren V, et al. The acute hemodynamic effects of intravenous verapamil in coronary artery disease. Assessment by equilibrium-gated radionuclide ventriculography. Circulation 1983 Jan; 67: 101–10

    PubMed  CAS  Google Scholar 

  3. Johnston DL, Gebhardt VA, Donald A, et al. Comparative effects of propranolol and verapamil alone and in combination on left ventricular function and volumes in patients with chronic exertional angina: a double-blind, placebo-controlled, randomized, crossover study with radionuclide ventriculography. Circulation 1983 Dec; 68: 1280–9

    PubMed  CAS  Google Scholar 

  4. Chew CYC, Brown G, Singh BN, et al. Effects of verapamil on coronary hemodynamic function and vasomobility relative to its mechanism of antianginal action. Am J Cardiol 1983; 51: 699–705

    PubMed  CAS  Google Scholar 

  5. Ferlinz J, Easthope J, Arnow WS. Effects of verapamil on myocardial performance in coronary disease. Circulation 1979; 59: 313–9

    PubMed  CAS  Google Scholar 

  6. Vlietstra RE, Farias MAC, Frye RL, et al. Effect of verapamil on left ventricular function: a randomised placebo-controlled study. Am J Cardiol 1983; 51: 1213–7

    PubMed  CAS  Google Scholar 

  7. Silke B, Verma SP, Nelson GI, et al. The effects on left ventricular performance of nifedipine and verapamil in exercise-induced angina pectoris. Br J Clin Pharmacol 1984 Jun; 17: 735–43

    PubMed  CAS  Google Scholar 

  8. Myreng Y, Myhre E. Effects of verapamil on left ventricular relaxation and filling dynamics in coronary artery disease: a study by pulsed Doppler echocardiography [see comments]. Am Heart J 1989 Apr; 117: 870–5

    PubMed  CAS  Google Scholar 

  9. Nishimura RA, Schwartz RS, Holmes JDR. Failure of calcium channel blockers to improve ventricular relaxation in humans. J Am Coll Cardiol 1993 Jan; 21: 182–8

    PubMed  CAS  Google Scholar 

  10. Betocchi S, Piscione F, Perrone-Filardi P, et al. Effects of intravenous verapamil on left ventricular relaxation and filling in angina pectoris. Am J Cardiol 1990 Oct 1; 66: 818–25

    PubMed  CAS  Google Scholar 

  11. Ahmed JH, Elliott HL, Meredith PA. Low-dose verapamil in middle-aged and elderly patients with angina pectoris: no evidence of increased susceptibility to the cardiac effects. Cardiovasc Drugs Ther 1992 Apr; 6: 153–8

    PubMed  CAS  Google Scholar 

  12. Gill JB, Cairns JA, McEwan MP. Improved left ventricular performance during exercise with verapamil or nifedipine in patients with chronic stable angina. Am Heart J 1987 Mar; 113: 700–7

    PubMed  CAS  Google Scholar 

  13. Sadick NN, Tan ATH, Fletcher PJ, et al. A double-blind randomised trial of propranolol and verapamil in the treatment of effort angina. Circulation 1982; 66(3): 574–9

    PubMed  CAS  Google Scholar 

  14. Théroux P, Taeymans Y, Waters DD. Calcium antagonists: clinical use in the treatment of angina. Drugs 1983; 25: 178–95

    PubMed  Google Scholar 

  15. Ferlinz J, Turbow ME. Antianginal and myocardial metabolic properties of verapamil in coronary artery disease. Am J Cardiol 1982; 46: 1019–26

    Google Scholar 

  16. Rouleau J-L, Chatterjee K, Ports TA, et al. Mechanism of relief of pacing-induced angina with oral verapamil. Circulation 1983; 67: 94–100

    PubMed  CAS  Google Scholar 

  17. Soward AL, Vanhaleweyk GL, Serruys PW. The haemodynamic effects of nifedipine, verapamil and diltiazem in patients with coronary artery disease. A review. Drugs 1986 Jul; 32: 66–101

    PubMed  CAS  Google Scholar 

  18. Brodsky SJ, Cutler SS, Weiner DA, et al. Treatment of stable angina of effort with verapamil: a double-blind, placebo-controlled randomised crossover study. Circulation 1982; 66(3): 569–74

    PubMed  CAS  Google Scholar 

  19. Frishman WH, Klein NA, Strom JA, et al. Superiority of verapamil to propranolol in stable angina pectoris: a double-blind, randomised crossover trial. Circulation 1982; 65 (1 Pt 2): 51–9

    Google Scholar 

  20. De Divitiis O, Liguori V, Di Somma S, et al. Bisoprolol in the treatment of angina pectoris: a double blind comparison with verapamil. Eur Heart J 1987 Dec; 8 Suppl M: 43–54

    PubMed  Google Scholar 

  21. Rodrigues EA, Kohli RS, Hains AD, et al. Comparison of nicardipine and verapamil in the management of chronic stable angina. Int J Cardiol 1988 Mar; 18: 357–69

    PubMed  CAS  Google Scholar 

  22. Bala Subramanian VB, Bowles MJ, Khurmi NS, et al. Evaluation of verapamil and high dose nifedipine in patients with chronic stable angina with objective methods. Acta Med Scand Suppl 1984; 681: 61–73

    Google Scholar 

  23. Sigurd B, Hansen JF. Verapamil or propranolol in the treatment of stable angina pectoris of effort. Acta Med Scand Suppl 1984; 681: 75–81

    PubMed  CAS  Google Scholar 

  24. Lesbre JP, Lalau JD, Jaubourg ML, et al. Verapamil versus propranolol in stable effort angina. Randomized, crossed, double-blind study [in French]. Ann Cardiol Angeiol Paris 1988 Apr; 37: 205–10

    PubMed  CAS  Google Scholar 

  25. Levantesi D, Marraccini P, Michelassi C. Elective response to propranolol or verapamil in ischemia on effort. Can J Cardiol 1989 Sep; 5: 299–304

    PubMed  CAS  Google Scholar 

  26. Singh BN, Chey CYC, Josephson MA, et al. Pharmacologic and hemodynamic mechanisms underlying the antianginal actions of verapamil. Am J Cardiol 1982; 50: 886–93

    PubMed  CAS  Google Scholar 

  27. Fleckenstein-Grün G, Frey M, Thimm F, et al. Differentiation between calcium- and cholesterol-dominated types of arteriosclerotic lesions: antiarteriosclerotic aspects of calcium antagonists. J Cardiovasc Pharmacol 1991; 18 Suppl 6: S1–9

    PubMed  Google Scholar 

  28. Nayler WG. The molecular basis for the use of calcium antagonists in ischaemic heart disease. Drugs 1992; 43 Suppl. 1: 21–7

    PubMed  Google Scholar 

  29. Nayler WG, Ferrari R, Williams A. Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischeamic and reperfused myocardium. Am J Cardiol 1980 Aug; 46: 242–8

    PubMed  CAS  Google Scholar 

  30. Weinstein GS, Rao PS, Tyras DH. Reduction of myocardial injury with verapamil before aortic cross-clamping. Ann Thorac Surg 1990 Mar; 49: 419–23

    PubMed  CAS  Google Scholar 

  31. Werner GS, Schmid M, Klein HH, et al. The cardioprotective effect of verapamil during percutaneous transluminal coronary angioplasty [in German]. Z Kardiol 1988 Nov; 77: 728–35

    PubMed  CAS  Google Scholar 

  32. El-Khoury F, Maarek M, Jean M, et al. Electrocardiographic evaluation of the anti-ischemic effects of verapamil during angioplasty [in French]. Ann Cardiol Angeiol 1994 Jun; 43: 351–6

    CAS  Google Scholar 

  33. Bussmann WD, Seher W, Gruengras M. Reduction of creatine kinase and creatine kinase-MB indexes of infarct size by intravenous verapamil. Am J Cardiol 1984 Dec 1; 54: 1224–30

    PubMed  CAS  Google Scholar 

  34. Kloner RA, Braunwald E. Effects of calcium antagonists on infarction myocardium. Am J Cardiol 1987 Jan 30; 59: 84B–94B

    PubMed  CAS  Google Scholar 

  35. Heide RSV, Schwartz LM, Reimer KA. The novel calcium antagonist Ro 40-5967 limits myocardial infarct size in the dog. Cardiovasc Res 1994 Oct; 28: 1526–32

    Google Scholar 

  36. Sullivan AT, Baker DJ, Drew GM. Effect of calcium channel blocking agents on infarct size after ischaemia-reperfusion in anaesthetised pigs: relationship between cardioprotection and cardiodepression. J Cardiovasc Pharmacol 1991 May; 17: 707–17

    PubMed  CAS  Google Scholar 

  37. Mrak RE, Carry MM, Murphy ML, et al. Reperfusion injury in ischemic myocardium: effects of nifedipine and verapamil. Am J Cardiovasc Pathol 1990; 3: 61–8

    PubMed  CAS  Google Scholar 

  38. Richard V, Tron C, Blanc T, et al. Infarct size-limiting properties of Ro 40-5967, a novel nondihydropyridine calcium channel, in anesthetized rats: comparison with verapamil. J Cardiovasc Pharmacol 1995 Apr; 25: 552–7

    PubMed  CAS  Google Scholar 

  39. Wolfe CL, Donnelly TJ, Sievers R, et al. Myocardial protection with verapamil during ischaemia and reperfusion: dissociation between myocardial salvage and the degree of ATP depletion during ischaemia. Cardiovasc Res 1991 Feb; 25: 101–9

    PubMed  CAS  Google Scholar 

  40. Adachi T, Miura T, Noto T, et al. Does verapamil limit myocardial infarct size in a heart deficient in xanthine oxidase? Clin Exp Pharmacol Physiol 1990 Nov; 17: 769–79

    PubMed  CAS  Google Scholar 

  41. Przyklenk K, Kloner RA. Effect of verapamil on postischemic ‘stunned’ myocardium: importance of the timing of treatment. J Am Coll Cardiol 1988 Mar; 11: 614–23

    PubMed  CAS  Google Scholar 

  42. Reifart N, Marston W, Zierler MK, et al. Effects of bepridil on regional myocardial ischemia and comparison with verapamil. Am J Cardiol 1986 Sep 1; 58: 541–6

    PubMed  CAS  Google Scholar 

  43. Tillmanns H, Neumann FJ, Parekh N, et al. Pharmacologic effects on coronary microvessels during myocardial ischaemia. Eur Heart J 1990 Apr; 11 Suppl. B: 10–5

    PubMed  CAS  Google Scholar 

  44. Fuster V, Badimon L, Badimon JJ, et al. The pathogenesis of coronary artery disease and the acute coronary syndromes (first of two parts). N Engl J Med 1992; 326 (Jan 23): 242–50

    PubMed  CAS  Google Scholar 

  45. Fuster V, Badimon L, Badimon JJ, et al. The pathogenesis of coronary artery disease and the acute coronary syndromes (second of two parts). N Engl J Med 1992; 326 (Jan 30): 310–8

    PubMed  CAS  Google Scholar 

  46. Bonebrake FC, Bertha B, Folts JD. Verapamil combined with aspirin for inhibiting epinephrine-stimulated platelet thrombus formation in stenosed canine coronary arteries. Coron Artery Dis 1991 Jun; 2: 487–92

    Google Scholar 

  47. McTavish D, Sorkin EM. Verapamil: an updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension. Drugs 1989; 38(1): 19–76

    PubMed  CAS  Google Scholar 

  48. Schömig A, Rehmert G, Kurz T, et al. Calcium antagonism and norepinephrine release in myocardial ischemia. J Cardiovasc Pharmacol 1992; 20 Suppl. 7: 16–20

    Google Scholar 

  49. Wallén NH, Held C, Rehnqvist N, et al. Platelet aggregability in vivo is attenuated by verapamil but not by metoprolol in patients with stable angina pectoris. Am J Cardiol 1995 Jan 1; 75: 1–6

    PubMed  Google Scholar 

  50. Rouleau JL, Chatterjee K, Parmley WW, et al. Myocardial catecholamine balance during angina: effects of calcium entry blockers, verapamil and nifedipine. Am Heart J 1985 Feb; 109: 201–9

    PubMed  CAS  Google Scholar 

  51. Swies J, Omogbai EKI, Smith GM. Occlusion and reperfusion-induced arrhythmias in rats: involvement of platelets and effects of calcium antagonists. J Cardiovasc Pharmacol 1990 May; 15: 816–25

    PubMed  CAS  Google Scholar 

  52. Brocchieri A, Saporiti A, Pacchiarini L, et al. Activation of platelets by ADP, collagen or thrombin: effect of the calcium channel blocker verapamil [abstract no. 2089]. Thromb Haemost 1995; 73(6): 1447

    Google Scholar 

  53. Walkowiak B, Koziolkiewicz W, Michalec L, et al. Changes in platelet response to ADP caused by verapamil [abstract no. 2097]. Thromb Haemost 1995; 73(6): 1449

    Google Scholar 

  54. L-Lacoste L, Lam JYT, Hung J, et al. Oral verapamil inhibits platelet thrombus formation in humans. Circulation 1994 Feb; 89: 630–4

    PubMed  CAS  Google Scholar 

  55. Górski J, Nowak J, Slonecka A, et al. Inhibition by verapamil of platelet membrane aggregation may protect patients with IHD and hypertension from atherosclerosis [abstract]. Atherosclerosis 1994 Sep 15; 109: 275

    Google Scholar 

  56. Gadzhiev A, Kubatiev A, Naumov V, et al. Effects of nifedipine, diltiazem and verapamil on platelet aggregation: comparative study in healthy donors and patients with congestive heart failure [abstract]. J Heart Fail 1993 May; 1 Suppl.: abstr.519

  57. Orekhov AN, Baldenkov GN, Tertov VV, et al. Cardiovascular drugs and atherosclerosis: effects of calcium antagonists, β-blockers, and nitrates on atherosclerotic characteristics of human aortic cells. J Cardiovasc Pharmacol 1988; 12 Suppl. 6: 66–8

    Google Scholar 

  58. Blumlein SL, Sievers R, Kidd P, et al. Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit. Am J Cardiol 1984 Oct 1; 54: 884–9

    PubMed  CAS  Google Scholar 

  59. Parmley WW. Vascular protection from atherosclerosis: potential of calcium antagonists. Am J Cardiol 1990 Dec 18; 66: 16–22

    CAS  Google Scholar 

  60. Strunge P, Engby B, Schmidt E, et al. Variation of serum lipoproteins in postmyocardial infarction patients treated with verapamil or placebo. Acta Med Scand Suppl 1984; 681: 53–7

    PubMed  CAS  Google Scholar 

  61. Walldius G. Effect of verapamil on serum lipoproteins in patients with angina pectoris. Acta Med Scand Suppl. 1984; 681: 43–8

    PubMed  CAS  Google Scholar 

  62. Barnes C, Hamilton PG, Lebel M. Effects of monotherapy with sustained-release verapamil on blood pressure, lipid levels, renal function, diabetic control, and patient well-being in patients with mild to moderate hypertension. Curr Ther Res 1993 Aug; 54: 127–41

    Google Scholar 

  63. Catalano M, Cislaghi C, Carzaniga G, et al. Effects of treatment with verapamil SR and captopril on the lipid profile of hypertensive patients. Drugs 1992; 44 Suppl. 1: 88–93

    PubMed  Google Scholar 

  64. Lewis GRJ. Long-term results with verapamil in essential hypertension and its influence on serum lipids. Am J Cardiol 1986 Feb 26; 57: 35D–8D

    PubMed  CAS  Google Scholar 

  65. Fleckenstein-Grün G, Thimm F, Frey M. Progression and regression by verapamil of vitamin D3-induced calcific medial degeneration in coronary arteries of rats. J Cardiovasc Pharmacol 1995 Aug; 26: 207–13

    PubMed  Google Scholar 

  66. Conrad K, Barbee RW, Maymind M, et al. Verapamil decreases early signs of atherosclerosis more than captopril in the diabetic hypertensive rat [abstract]. Am J Hypertens 1993 May; 6: 41A

    Google Scholar 

  67. Zhu B-Q, Sievers RE, Isenberg WM, et al. Regression of atherosclerosis in cholesterol-fed rabbits: effects of fish oil and verapamil. J Am Coll Cardiol 1990 Jan; 15: 231–7

    PubMed  CAS  Google Scholar 

  68. Orekhov AN, Pivovarova EM, Sobenin IA, et al. Use of cell culture for optimisation of direct antiatherogenic therapy with verapamil. Drugs 1992; 44 Suppl. 1: 105–10

    PubMed  Google Scholar 

  69. Orekhov AN. In vitro models of anti-atherosclerotic effects of cardiovascular drugs. Am J Cardiol 1990 Dec 18; 66: 231–81

    Google Scholar 

  70. Orekhov AN, Tertov VV, Khashimov KA, et al. Antiatherosclerotic effects of verapamil in primary culture of human aortic intimai cells. J Hypertens 1986; 4 Suppl. 6: S153–5

    CAS  Google Scholar 

  71. Orekhov AN, Tertov VV, Lyakishev AA, et al. Use of cultured atherosclerotic cells for investigation of antiatherosclerotic effects of anipamil and other calcium antagonists. J Hum Hypertens 1991 Oct; 5: 425–30

    PubMed  CAS  Google Scholar 

  72. Midtbo KA. Effects of long-term verapamil therapy on serum lipids and other metabolic parameters. Am J Cardiol 1990 Dec 18; 66: 13–5

    Google Scholar 

  73. Libretti A, Catalano M. Lipid profile during antihypertensive treatment. The SLIP Study Group. Drugs 1993; 46 Suppl. 2: 16–23

    PubMed  Google Scholar 

  74. Held C, Hlemdahl P, Rehnqvist N, et al. Short-term treatment effects of metoprolol or verapamil on haemostatic markers, catecholamines and lipids in patients with stable angina pectoris. Eur Heart J 1995; 16 Abstract Supplement: 468

    Google Scholar 

  75. Husum D, Johnsen A, Jensen G. Requirements for drug monitoring of verapamil: experience from an unselected group of patients with cardiovascular disease. Pharmacol Toxicol 1990 Mar; 66: 163–9

    PubMed  CAS  Google Scholar 

  76. Tartaglione TA, Pieper JA, Lopez LL, et al. Pharmacokinetics of verapamil and norverapamil during long-term oral therapy. Res Commun Chem Pathol Pharmacol 1983 Apr; 40: 15–27

    PubMed  CAS  Google Scholar 

  77. Fuenmayor NT, Faggin BM, Cubeddu LX. Comparative efficacy, safety and pharmacokinetics of verapamil SR vs verapamil IR in hypertensive patients. Drugs 1992; 44 Suppl. 1: 1–11

    PubMed  Google Scholar 

  78. Jespersen CM, Frederiksen M, Hansen JF, et al. Circadian variation in the pharmacokinetics of verapamil. Eur J Clin Pharmacol 1989; 37: 613–5

    PubMed  CAS  Google Scholar 

  79. Rumiantsev DO, Piotrovskii VK, Metelitsa VI, et al. Serum binding of nifedipine and verapamil in patients with ischaemic heart disease on monotherapy. Br J Clin Pharmacol 1989 Sep; 28: 357–61

    PubMed  CAS  Google Scholar 

  80. John DN, Fort S, Lewis MJ. Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers. Br J Clin Pharmacol 1992 Jun; 33: 623–7

    PubMed  CAS  Google Scholar 

  81. Schwartz JB. Aging alters verapamil elimination and dynamics: single dose and steady-state responses. J Pharmacol Exp Ther 1990 Oct; 255: 364–73

    PubMed  CAS  Google Scholar 

  82. Somogyi A, Albrecht M, Kliems G, et al. Pharmacokinetics, bioavailablity and ECG response of vereapamil in patients with liver cirrhosis. Br J Clin Pharmacol 1981; 12: 51–60

    PubMed  CAS  Google Scholar 

  83. Powell AC, Elliott SL, Horowitz JD. Verapamil in unstable angina pectoris: failure to demonstrate a relationship between efficacy and plasma levels. Ther Drug Monit 1988; 10: 34–8

    PubMed  CAS  Google Scholar 

  84. Picca M, Azzollini F, Cereda A, et al. Comparison of the antianginal efficacy of four calcium antagonists and propranolol in stable angina pectoris. Eur J Clin Pharmacol 1989 Oct; 37: 325–31

    PubMed  CAS  Google Scholar 

  85. Leon MB, Rosing DR, Lipson RO, et al. Clinical efficacy of verapamil alone and combined with propranolol in treating patients with chronic stable angina pectoris. Am J Cardiol 1981 July; 48: 131–8

    PubMed  CAS  Google Scholar 

  86. Cutler NR, Anders RJ, Jhee SS, et al. Placebo-controlled evaluation of three doses of a controlled-onset, extended-release formulation of verapamil in the treatment of stable angina pectoris. Am J Cardiol 1995 Jun 1; 75: 1102–6

    PubMed  CAS  Google Scholar 

  87. Kohli RS, Rodrigues EA, Hughes LO, et al. Sustained release verapamil, a once daily preparation: objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina. J Am Coll Cardiol 1987 Mar; 9: 615–21

    PubMed  CAS  Google Scholar 

  88. Vandenburg M, Dews I, Gibbs J, et al. Sustained release verapamil in chronic stable angina pectoris: a multicentre randomised double-blind crossover design trial vs placebo [abstract]. Br J Clin Pharmacol 1990 Aug; 30: 340–1

    Google Scholar 

  89. Miller AJ, Grais IM, Kaminsky LA. The long-term treatment of stable angina pectoris with verapamil. J Clin Pharmacol 1990 Oct; 30: 916–21

    PubMed  CAS  Google Scholar 

  90. Acanfora D, De CL, Di PA, et al. Age-related changes of antianginal effects of verapamil in patients with stable effort angina. A medium term randomized double-blind placebo controlled trial. G Ital Cardiol 1993 May; 23: 451–8

    PubMed  CAS  Google Scholar 

  91. Foale RA, Vandenburg MJ. Sustained-release verapamil and nifedipine in exercise-induced angina pectoris. Eur Heart J 1992 Feb; 13: 256–60

    PubMed  CAS  Google Scholar 

  92. Winniford MD, Fulton KL, Corbett JR, et al. Propranolol-verapamil versus propranolol-nifedipine in severe angina pectoris of effort: a randomized, double-blind, crossover study. Am J Cardiol 1985 Feb 1; 55: 281–5

    PubMed  CAS  Google Scholar 

  93. Lablanche JM, Gommeaux A, Fourrier JL, et al. Cross-over double-blind study of verapamil versus diltiazem in effort myocardial ischemia [in French]. Ann Cardiol Angeiol Paris 1989 May; 38: 281–4

    PubMed  CAS  Google Scholar 

  94. Nielsen HK, Krusell LR, Husted SE, et al. Bepridil versus verapamil in stable angina pectoris — a controlled clinical trial. Int J Cardiol 1989 Jun; 23: 357–64

    PubMed  CAS  Google Scholar 

  95. Matteoli S, Trappolini M, Galli V, et al. Bepridil in stable angina of effort: a double-blind comparison with verapamil [in Italian]. Cardiologia 1988 Apr; 33: 413–8

    PubMed  CAS  Google Scholar 

  96. Eichstaedt H, Danne O, Raab E, et al. Comparative measurements of gallopamil and verapamil in the treatment of ischaemic heart disease. Acta Ther 1990 Jan; 16: 29–41

    Google Scholar 

  97. Molinero E, Salcedo A, Sagastagoitia JD, et al. Treatment of transient myocardial ischemia in patients with stable angina: a comparative study of verapamil slow-release and nifedipine plus propranolol. J Cardiovasc Pharmacol 1992 Apr; 19: 650–3

    PubMed  CAS  Google Scholar 

  98. Winniford MD, Huxley RL, Hillis LD. Randomized, double-blind comparison of propranolol alone and a propranolol-verapamil combination in patients with severe angina of effort. J Am Coll Cardiol 1983 Feb; 1 (2 Pt 1): 492–8

    PubMed  CAS  Google Scholar 

  99. Silber S, Vogler A, Theisen K. Equal anti-ischemic properties of isosorbide dinitrate plus verapamil and isosorbide dinitrate plus propranolol. A randomized, double-blind and crossover study. Z Kardiol 1986; 75 Suppl 3: 100–5

    PubMed  Google Scholar 

  100. Lessem J. Combined therapy with Ca-antagonists and beta-adrenergic receptor blocking agents in chronic stable angina. Acta Med Scand Suppl 1984; 681: 83–90

    PubMed  CAS  Google Scholar 

  101. Findlay IN, MacLeod K, Gillen G, et al. A double blind placebo controlled comparison of verapamil, atenolol, and their combination in patients with chronic stable angina pectoris. Br Heart J 1987 Apr; 57: 336–43

    PubMed  CAS  Google Scholar 

  102. Bowles MJ, Bala-Subramanian V, Davies AB, et al. Double-blind randomized crossover trial of verapamil and propranolol in chronic stable angina. Am Heart J 1983 Dec; 106: 1297–306

    PubMed  CAS  Google Scholar 

  103. Johnson SM, Mauritson DR, Corbett JR, et al. Double-blind randomised, placebo-controlled comparison of propranolol and verapamil in the treatment of patinets with stable angina pectoris. Am J Med 1981 September; 71: 443–51

    PubMed  CAS  Google Scholar 

  104. Hopkinson ND, Hui KP, Smith MP. A comparison of sustained release verapamil versus atenolol for 24 h protection from exercise-induced angina pectoris. Eur Heart J 1991 Dec; 12: 1273–7

    PubMed  CAS  Google Scholar 

  105. Forslund L, Björkander I, Ericksson S, et al. Effects of metoprolol or verapamil treatment on results from exercise testing and long-term electrocardiogram recordings in stable angina pectoris. Short-term results from the APSIS study. Eur Heart J 1995; 16 Abstract Supplement: 422

    Google Scholar 

  106. Friedensohn A, Meshulam R, Schlesinger Z. Randomized double-blind comparison of the effects of isosorbide dinitrate retard, verapamil sustained-release, and their combination on myocardial ischemic episodes. Cardiology 1991; 79 Suppl. 2: 31–40

    PubMed  Google Scholar 

  107. Schneider W, Maul FD, Bussmann WD, et al. Comparison of the antianginal efficacy of isosorbide dinitrate (ISDN) 40 mg and verapamil 120 mg three times daily in the acute trial and following two-week treatment. Eur Heart J 1988 Feb; 9: 149–58

    PubMed  CAS  Google Scholar 

  108. Jespersen CM, Klitgaard NA, Nielsen H, et al. Sustained-release and instant-release verapamil in treatment of angina pectoris. Eur J Clin Pharmacol 1989; 36: 625–7

    PubMed  CAS  Google Scholar 

  109. Pellinen TJ, Lukkala K, Sundberg S, et al. Efficacy of conventional and sustained-release verapamil in stable angina pectoris. Ann Med 1992; 24: 49–53

    PubMed  CAS  Google Scholar 

  110. Tan AT, Quek S. Verapamil administered twice daily in stable angina pectoris. Chest 1984 Jan; 85: 55–8

    PubMed  CAS  Google Scholar 

  111. Weiner DA, Klein MD, Cutler SS. Efficacy of sustained-release verapamil in chronic stable angina pectoris. Am J Cardiol 1987 Feb 1; 59: 215–8

    PubMed  CAS  Google Scholar 

  112. Weiner DA, McCabe CH, Cutler SS, et al. Efficacy and safety of verapamil in patients with angina pectoris after 1 year of continuous, high-dose therapy. Am J Cardiol 1983 May 1; 51: 1251–5

    PubMed  CAS  Google Scholar 

  113. Zanolla L, Trevi GP, Rizzo A, et al. Long-term persistence of antianginal effect of oral verapamil in chronic stable angina. J Cardiovasc Pharmacol 1984 May-Jun; 6: 423–8

    PubMed  CAS  Google Scholar 

  114. Parodi O, Simonetti I, L’Abbate A, et al. Verapamil versus propranolol for angina at rest. Am J Cardiol 1982 October; 50: 923–8

    PubMed  CAS  Google Scholar 

  115. Parodi O, Simonetti I, Michelassi C, et al. Comparison of verapamil and propranolol therapy for angina pectoris at rest: a randomized, multiple-crossover, controlled trial in the coronary care unit. Am J Cardiol 1986 Apr 15; 57: 899–906

    PubMed  CAS  Google Scholar 

  116. Capucci A, Bassein L, Bracchetti D, et al. Propranolol v. verapamil in the treatment of unstable angina. A double-blind cross-over study. Eur Heart J 1983 Mar; 4: 148–54

    PubMed  CAS  Google Scholar 

  117. Rizzon P, Scrutinio D, Mangini SG, et al. Randomized placebo-controlled comparative study of nifedipine, verapamil and isosorbide dinitrate in the treatment of angina at rest. Eur Heart J 1986 Jan; 7: 67–76

    PubMed  CAS  Google Scholar 

  118. Singh N, Mironov D, Goodman S, et al. Treatment of silent ischemia in unstable angina: a randomized comparison of sustained-release verapamil versus metoprolol [abstract]. J Am Coll Cardiol 1995 (special issue): 88-9

  119. Maresta A, Marzocchi A, Capucci A, et al. Nifedipine compared with verapamil in unstable angina pectoris. Int J Clin Pharmacol Res 1986; 6: 291–301

    PubMed  CAS  Google Scholar 

  120. The Israeli Sprint Study Group. Secondary prevention reinfarction Israeli nifedipine trial (SPRINT). A randomised intervention trial of nifedipine in patients with acute myocardial infarction. Eur Heart J 1988; 9: 354–64

    Google Scholar 

  121. Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl J Med 1988 Aug 18; 319(7): 385–92

    Google Scholar 

  122. Held PH, Yusuf S, Furberg CD. Calcium channel blockers in acute myocardial infarction and stable angina: an overview. BMJ 1989 Nov 11; 299: 1187–92

    PubMed  CAS  Google Scholar 

  123. Lichtlen PR, Hugenholtz PG, Rafflenbuel W, et al. Retardation of angiographic progression of coronary artery disease by nifedipine. Results of the International Nifedipine Trial on Anti-atherosclerotic Therapy (INTACT). Lancet 1990 May 12; 335: 1109–11

    PubMed  CAS  Google Scholar 

  124. Held PH, Yusuf S. Effects of beta-blockers and calcium channel blockers in acute myocardial infarction. Eur Heart J 1993 Oct; 14 Suppl. F: 18–25

    PubMed  Google Scholar 

  125. Boden WE, Krone RJ, Kleiger RE, et al. Electrocardiographic subset analysis of diltiazem administration on long term outcome after acute myocardial infarction. Am J Cardiol 1991 Feb 15; 67(5): 335–42

    PubMed  CAS  Google Scholar 

  126. Hansen JE Secondary prevention with calcium antagonists after acute myocardial infarction. Drugs 1992; 44 Suppl 1: 33–43

    PubMed  Google Scholar 

  127. Persson S. Calcium antagonists in secondary prevention after myocardial infarction. Drugs 1991; 42 Suppl. 2: 54–60

    PubMed  Google Scholar 

  128. Danish SG on V in MI. Verapamil in acute myocardial infarction. Am J Cardiol 1984; 54: 24–8

    Google Scholar 

  129. Danish SG on V in MI. Verapamil in acute myocardial infarction. Eur Heart J 1984; 5: 516–28

    Google Scholar 

  130. Danish SG on V in MI. Effect of verapamil on mortality and major events after acute myocardial infarction (The Danish Verapamil Infarction Trial II — DAVIT II). Am J Cardiol 1990 Oct 1; 66: 779–85

    Google Scholar 

  131. Hansen JF. Treatment with verapamil after an acute myocardial infarction. Review of the Danish studies on verapamil in myocardial infarction (DAVIT I and II). Drugs 1991; 42 Suppl 2: 43–53

    PubMed  Google Scholar 

  132. Danish SG on V in MI. Treatment with verapamil after an acute myocardial infarction: a review of the Danish studies on verapamil in myocardial infarction (DAVIT I and II). Cardiovasc Rev Rep 1993 May; 14: 32–42

    Google Scholar 

  133. Hansen JF et al. Treatment with verapamil during and after an acute myocardial infarction: a review based on the Danish Verapamil Infarction Trials I and II. J Cardiovasc Pharmacol 1991; 18 Suppl. 6: 20–5

    Google Scholar 

  134. Danish SG on V in MI. Secondary prevention of death and reinfarction with verapamil after an acute myocardial infarction. J Hum Hypertens 1990 Dec; 4 Suppl. 5: 19–25

    Google Scholar 

  135. Hansen JF. Review of postinfarct treatment with verapamil: combined experience of early and late intervention studies with verapamil in patients with acute myocardial infarction. Cardiovasc Drugs Ther 1994 Aug; 8 Suppl. 3: 543–7

    PubMed  Google Scholar 

  136. Jespersen CM, Fischer HJ, Spange ML. The prognostic significance of post-infarction angina pectoris and the effect of verapamil on the incidence of angina pectoris and prognosis. Eur Heart J 1994 Feb; 15: 270–6

    PubMed  CAS  Google Scholar 

  137. Vaage-Nilsen M, Rasmussen V, Holländer NH. Prevalence of transient myocardial ischaemia during the first year after a myocardial infarction. Effect of treatment with verapamil. Eur Heart J 1992 May; 13: 666–70

    PubMed  CAS  Google Scholar 

  138. Anderson LT, Sigurd B, Fischer Hansen J, et al. Verapamil and circadian variation of sudden cardiac death. Am Heart J In press

  139. Rehnqvist N, Hjemdahl P, Billing E, et al. Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS). Eur Heart J 1996; 17: 1–7

    Google Scholar 

  140. Rehnqvist N, Hjemdahl P, Billing E, et al. Prevention of cardiac events in patients with angina pectoris: results of the APSIS study [abstract]. Eur Heart J 1995 Aug; 16 Suppl. H: 18

    Google Scholar 

  141. Liu MW, Roubin GS, King SB. Restenosis after coronary angioplasty. Potential biologic determinants and role of intimai hyperplasia. Circulation 1989; 79: 1374–87

    PubMed  CAS  Google Scholar 

  142. Kober G, Vallbracht C, Kadel C, et al. Results of repeat angiography up to eight years following percutaneous transluminal angioplasty. Eur Heart J 1989; 10 Suppl. G: 49–53

    PubMed  Google Scholar 

  143. Stein O, Halperin G, Stein Y. Long term effects of verapamil on aortic smooth muscle cells cultured in the presence of hypercholesterolemic serum. Arteriosclerosis 1987; 7: 585–92

    PubMed  CAS  Google Scholar 

  144. Block LH, Emmons LR, Vogt E, et al. Calcium channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle. Med Sci 1989; 86: 2388–92

    CAS  Google Scholar 

  145. Hoberg E, Dietz R, Frees U, et al. Verapamil treatment after coronary angioplasty in patients at high risk of recurrent stenosis. Br Heart J 1994 Mar; 71: 254–60

    PubMed  CAS  Google Scholar 

  146. Bentivoglio LG, Leo LR, Wolf NM, et al. Frequency and importance of unprovoked coronary artery spasm in patients with angina pectoris undergoing percutaneous transluminal coronary angioplasty. Am J Cardiol 1983; 51: 1067–71

    PubMed  CAS  Google Scholar 

  147. Dorros G, Cowley MJ, Simpson J, et al. Persutaneous transluminal coronary angioplasty: report of complications from the National heart, Lung, and Blood Institute PTCA Registry. Circulation 1983; 67: 723–30

    PubMed  CAS  Google Scholar 

  148. Babbitt DG, Perry JM, Forman MB. Intracoronary verapamil for reversal of refractory coronary vasospasm during percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1988 Nov; 12: 1377–81

    PubMed  CAS  Google Scholar 

  149. Pomerantz RM, Kuntz RE, Diver DJ, et al. Intracoronary verapamil for the treatment of distal microvascular coronary artery spasm following PTCA. Cathet Cardiovasc Diagn 1991 Dec; 24: 283–5

    PubMed  CAS  Google Scholar 

  150. Piana RN, Paik GY, Cohen DJ, et al. Intracoronary verapamil for ‘no reflow’ following PTCA [abstract 3160]. Circulation 1993; 88 (4 pt 2): 1–587

    Google Scholar 

  151. Danish SG on V in ML Secondary prevention with verapamil after myocardial infarction. Am J Cardiol 1990 Dec 18; 66: 33–40

    Google Scholar 

  152. Arstall MA, Beltrame JF, Mohan P, et al. Incidence of adverse events during treatment with verapamil for suspected acute myocardial infarction. Am J Cardiol 1992 Dec 15; 70: 1611–2

    PubMed  CAS  Google Scholar 

  153. McGourty JC, Silas JH, Solomon SA. Tolerability of combined treatment with verapamil and beta-blockers in angina resistant to monotherapy. Postgrad Med J 1985 Mar; 61: 229–32

    PubMed  CAS  Google Scholar 

  154. Gonski PN. Stevens-Johnson syndrome induced by verapamil. Med J Aust 1992 May 4; 156: 672

    PubMed  CAS  Google Scholar 

  155. Lin AYF, Baker BA. Verapamil-associated Stevens-Johnson syndrome. Drug Intell Clin Pharm 1989 Dec; 23: 987–8

    CAS  Google Scholar 

  156. Kurkcuoglu N, Alaybeyi F. Erythema multiforme after verapamil treatment. J Am Acad Dermatol 1991 Mar; 24: 511–2

    PubMed  CAS  Google Scholar 

  157. Drenth JPH, Michiels JJ, Van JT. Verapamil-induced secondary erythermalgia. Br J Dermatol 1992 Sep; 127: 292–4

    PubMed  CAS  Google Scholar 

  158. Pritza DR, Bierman MH, Hammeke MD. Acute toxic effects of sustained-release verapamil in chronic renal failure. Arch Intern Med 1991 Oct; 151: 2081–4

    PubMed  CAS  Google Scholar 

  159. Psaty B. Calcium antagonists; a new study warns of adverse effects. Case-control study presented at the American Heart Association Conference on Cardiovascular disease, Epidemiology and Prevention, San Antonio, Texas, March 1995. In-pharma 1995 Mar 25; No. 979: 3–5

    Google Scholar 

  160. Verapamil meta-analysis sponsored by Searle suggests “no evidence of harm”; case control study condradicts Psaty conclusion of higher MI risk with CCBs. FDC Rep Pink Sheet 1996 Jan 29: 6

  161. Watling SM, Crain JL, Edwards TD. Verapamil overdose: case report and review of the literature. Ann Pharmacother 1992 Nov; 26: 1373–8

    PubMed  CAS  Google Scholar 

  162. Horowitz BZ, Rhee KJ. Massive verapamil ingestion. Am J Emerg Med 1989 Nov; 7: 624–31

    PubMed  CAS  Google Scholar 

  163. Hofer CA, Smith JK, Tenholder MF. Verapamil intoxication: a literature review of overdoses and discussion of therapeutic options. Am J Med 1993 Oct; 95: 431–8

    PubMed  CAS  Google Scholar 

  164. Lip GYH, Ferner RE. Poisoning with anti-hypertensive drugs: calcium antagonists. J Hum Hypertens 1995 Mar; 9: 155–61

    PubMed  CAS  Google Scholar 

  165. Rosansky SJ. Verapamil toxicity — treatment with hemoperfusion. Ann Intern Med 1991 Feb 15; 114: 340–1

    PubMed  CAS  Google Scholar 

  166. Shah AR, Passalacqua BR. Case report: sustained-release verapamil overdose causing stroke: an unusual complication. Am J Med Sci 1992 Dec; 304: 357–9

    PubMed  CAS  Google Scholar 

  167. Sporer KA, Manning JJ. Massive ingestion of sustained-release verapamil with a concretion and bowel infarction. Ann Emerg Med 1993 Mar; 22: 603–5

    PubMed  CAS  Google Scholar 

  168. Doering W. Effect of coadministration of verapamil and quinidine on serum digoxin clearance. Eur J Clin Pharmacol 1983; 25: 517–21

    PubMed  CAS  Google Scholar 

  169. Pedersen KE, Christiansen BD, Kjaer K, et al. Verapamil-induced changes in digoxin kinetics and intraerythrocytic sodium concentration. Clin Pharmacol Ther 1983; 34: 8–13

    PubMed  CAS  Google Scholar 

  170. Rodin SM, Johnson BF, Wilson J, et al. Comparative effects of verapammil and isradipine on steady-state digoxin kinetics. Clin Pharmacol Ther 1988; 43: 668–72

    PubMed  CAS  Google Scholar 

  171. Hedman A, Angelin B, Arvidsson A, et al. Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans. Clin Pharmacol Ther 1991 Mar; 49: 256–62

    PubMed  CAS  Google Scholar 

  172. Klein HO, Kaplinsky E. Verapamil and digoxin: their respective effects on atrial fibrillation and their interaction. Am J Cardiol 1982; 50: 894–902

    PubMed  CAS  Google Scholar 

  173. Guerrero JR, Martin SS. Verapamil: full specrtum calcium channel blocking agent: an overview. Med Res Rev 1984; 4: 87–109

    PubMed  CAS  Google Scholar 

  174. McGoon MD, Vlietstra RE, Holmes DR, et al. The clinical use of verapamil. Mayo Clin Proc 1982; 57: 495–510

    PubMed  CAS  Google Scholar 

  175. Kuhlmann J. Effects of quinidine, verapamil and nifedipine on the pharmacokinetics and pharmacodynamics of digitoxin during steady state conditions. Arzneimittelforschung 1987; 37: 545–8

    PubMed  CAS  Google Scholar 

  176. Baky SH, Singh BN. Verapamil hydrochloride: pharmacological properties and the role in cardiovascular therapies. Pharmacotherapy 1982; 2: 328–53

    PubMed  CAS  Google Scholar 

  177. Findlay IN, Dargie HJ, Gillen G, et al. Effects on cardiac function, heart rate amd blood pressure during combination therapy with verapamil and atenolol. Br J Clin Pharmacol 1985; 19: 565–6

    Google Scholar 

  178. Hutchinson SJ, Lorimeer AR, Lakhdar A, et al. β-Blockers and verapamil: a cautionary tale. BMJ 1984; 289: 659–60

    PubMed  Google Scholar 

  179. Johnston DL, Lesoway R, Humen DP, et al. Clinical and haemodynamic evaluation of propranolol in combination with verapamil, nifedipine and diltiazem in exertional angina pectoris: a placebo-controlled, double-blind, randomised cross-over study. Am J Cardiol 1985; 55: 680–7

    PubMed  CAS  Google Scholar 

  180. Epstein SE, Rosing DR. Verapamil: its potential for causing serious complications in patients with hypertrophic cardiomyopathy. Circulation 1981; 64: 437–41

    PubMed  CAS  Google Scholar 

  181. Maisel AS, Motulsky HJ, Insel PA. Hypotension after quinidine plus verapamil. Possible additive competition at alpha-adrenergic receptors. N Engl J Med 1985 Jan 17; 312: 167–70

    PubMed  CAS  Google Scholar 

  182. Smith MS, Benyunes MC, Bjornsson TD, et al. The influence of cimetidine on the pharmacokinetics and the pharmacodynamics of verapamil. J Am Coll Cardiol 1984; 3: 568

    Google Scholar 

  183. Barbarash RA. Verapamil-rifampin interaction. Drug Intell Clin Pharm 1985; 19: 559–60

    PubMed  CAS  Google Scholar 

  184. Barbarash RA, Bauman JL, Fischer JH, et al. Near-total reduction in verapamil bioavailability by rifiamin. Chest 1988; 94: 954–9

    PubMed  CAS  Google Scholar 

  185. Mooy J, Böhm R, Van Baak M, et al. The influence of antituberculosis drugs on the plasma level of verapamil. Eur J Clin Pharmacol 1987; 32: 107–9

    PubMed  CAS  Google Scholar 

  186. MacPhee GJA, Mclnnes GT, Agnew E, et al. Clinically relevant adverse interaction between verapamil and carbamazepine in epileptic patients. Br J Clin Pharmacol 1986; 21: 569–70

    Google Scholar 

  187. Kishore K, Raina A, Misra V. Acute verapamil toxicity in a patient with chronic toxicity: possible interaction with ceftriaxone and clindamycin. Ann Pharmacother 1993 Jul-Aug; 27: 877–80

    PubMed  CAS  Google Scholar 

  188. Schulte-Sasse U, Hess W, Markschies-Hornung A, et al. Combined effects of halothane anesthesia and verapamil on systemic hemodynamics and left ventricular myocardial contractility in patients with ischemic heart disease. Anesth Analg 1984 Sep; 63: 791–8

    PubMed  CAS  Google Scholar 

  189. Buss J, Lasserre JJ, Heene DL. Asystole and cardiogenic shock due to combined treatment with verapamil and flecainide. Lancet 1992 Aug 29; 340: 546

    PubMed  CAS  Google Scholar 

  190. Gillis JC, Wagstaff AJ, Goa KL. Alteplase: a reappraisal of its pharmacological properties and therapeutic use in acute myocardial infarction. Drugs 1995 Jul; 50(1): 102–36

    PubMed  CAS  Google Scholar 

  191. Norwegian Multicenter Study Group. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 1981 April 2; 304(14): 801–7

    Google Scholar 

  192. Hansteen V, Moinichen E, Lorensten E, et al. One year’s treatment with propranolol after myocardial nninfarction: preliminary report of Norwegian Multicentre Trial. BMJ 1982; 284: 155–60

    PubMed  CAS  Google Scholar 

  193. Olsson G, Rehnqvist N, Sjögren A, et al. Long term treatment with metoprolol after myocardial infarction. Effect on 3 year mortality and morbidity. J Am Coll Cardiol 1985; 5: 1428–37

    PubMed  CAS  Google Scholar 

  194. Zannad F. Calcium antagonists: are they useful as additive therapy to thrombolysis in acute myocardial infarction? Drugs Today 1993; 29 Suppl. A: 19–25

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Rex N. Brogden & Paul Benfield

Authors
  1. Rex N. Brogden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Benfield
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Various sections of the manuscript reviewed by: R.W.F Campbell, Department of Cardiology, University of Newcastle, Newcastle upon Tyne, England; T. Endo, First Department of Internal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan; J. Fischer Hansen, Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; E. Freis, Hypertension Research Clinic, Veterans Affairs Medical Center, Washington, D.C., USA; O. Parodi, Istituto Di Fisiologica Clinica CNR, Pisa, Italy; E.L. Rose, BUPA North Cheshire Hospital, Warrington, Cheshire, England; T. Takabatake, Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Japan; N.H. Wallén, Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden; M.R. Weir, Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brogden, R.N., Benfield, P. Verapamil. Drugs 51, 792–819 (1996). https://doi.org/10.2165/00003495-199651050-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199651050-00007

Keywords

Search

Navigation