CNS Drugs

, Volume 12, Issue 2, pp 99–110 | Cite as

Nicotine Replacement Therapy in Patients with Coronary Heart Disease

Recommendations for Effective Use
  • Charlotta Pisinger
  • Poul Wennike
  • Philip Tønnesen
Disease Management


Cigarette smoking is a very important causative factor in cardiovascular disease (CVD). Smoking increases the risk of acute myocardial infarction, unstable angina and sudden death, and it is a risk factor for recurrent episodes of these diseases. It is well documented that patients with CVD who stop smoking, decrease their risk of future events markedly.

Smoking cessation is obviously very important in this category of patients, and it has been demonstrated in several trials that the use of nicotine replacement therapy (NRT) markedly improves the long term smoking cessation rates in healthy individuals, with further improvement in the rate if additional supportive adjunctive behavioural therapy is offered.

The use of NRT products for CVD patients has been, however, sparsely investigated: only 2 randomised placebo-controlled trials of NRT in these patients have been published. This fact, and the fact that nicotine has sympathomimetic effects, which lead to increased heart rate, increased blood pressure and coronary vasoconstriction, probably causes doctors to hesitate before using NRT products in this setting.

In this paper we review relevant literature on this subject and explore the efficacy and tolerability of NRT in CVD patients, which in this context is limited to patients with ischaemic heart diseases and arrhythmias. Patients with hypertension, stroke or peripheral vascular diseases are not discussed, due to lack of investigations in these fields.

We present recommendations for doses and duration of NRT in patients with CVD that, due to the few studies in this field, are mainly based on parallels from findings in healthy individuals. The conclusion of the 2 existing randomised placebo-controlled studies was that nicotine patches are well tolerated by patients with stable angina, and that the use of nicotine patches increases short term smoking cessation rates.


Nicotine Single Photon Emission Compute Tomography Adis International Limited Smoking Cessation Nicotine Replacement Therapy 
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  1. 1.
    Benowitz NL. Smoking-induced coronary vasoconstriction: implications for therapeutic use of nicotine. J Am Coll Cardiol 1993; 22(3): 648–9PubMedCrossRefGoogle Scholar
  2. 2.
    Department of Health and Human Services. The health consequences of smoking: cardiovascular disease: a report of the surgeon General. Washington, DC: Government Printing Office, 1983; (DHHS Publication no (PH5) 50204)Google Scholar
  3. 3.
    Benowitz NL, Steven G. Cardiovascular Toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol 1997; 29(7): 1422–31PubMedCrossRefGoogle Scholar
  4. 4.
    Allred EN, Bleecker ER, Chaitman BR, et al. Short-term effects of carbon monoxide exposure on the exercise performance of subjects with coronary artery disease. N Engl J Med 1989; 321(21): 1426–32PubMedCrossRefGoogle Scholar
  5. 5.
    Aronow WS, Cassidy J, Vangrow JS, et al. Effects of cigarette smoking and breathing carbon monoxide on cardiovascular hemodynamics in angial patients. Circulation 1974; 50: 340–7PubMedCrossRefGoogle Scholar
  6. 6.
    Calverly PMA, Leggett RJE, Flenley DC. Carbon monoxide and exercise tolerance in chronic bronchitis and emphysema. BMJ 1981; 283: 878–80CrossRefGoogle Scholar
  7. 7.
    Smith JR, Landaw SA. Smokers polycythemia. N Engl J Med 1978; 298: 6–10PubMedCrossRefGoogle Scholar
  8. 8.
    Stubbe I, Eskilsson J, Nilsson-Ehle P. High-density lipoprotein concentrations increase after stopping smoking. BMJ 1982; 284: 1511–3PubMedCrossRefGoogle Scholar
  9. 9.
    Kajser L, Berglund B. Effects of nicotine on coronary blood-flow in man. Clin Physiol 1985; 5: 541–52CrossRefGoogle Scholar
  10. 10.
    Palmer KJ, Brickley MM, Faulds D. Transdermal nicotine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an aid to smoking cessation. Drugs 1992; 44(3): 498–529Google Scholar
  11. 11.
    Porchet HC, Benowitz NL, Scheiner LB, et al. Apparent tolerance to the acute effect of nicotine results in part from distributionk inetics. J Clin Invest 1987; 80: 1466–71PubMedCrossRefGoogle Scholar
  12. 12.
    Fiore MC, Bailey WC, Cohen SJ, et al. Smoking cessation. Clinical practice guideline No 18, AHCPR 96-0692. Rock-ville: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1996Google Scholar
  13. 13.
    Silagy C, Mant D, Fowler G, et al. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet 1994; 343: 139–42PubMedCrossRefGoogle Scholar
  14. 14.
    Hjalmarson A. Effect of nicotine chewing gum in smoking cessation: a randomized, placebo-controlled, double-blind study. JAMA 1984; 252: 2835–8PubMedCrossRefGoogle Scholar
  15. 15.
    Hjalmarson A, Franzon M, Westin A, et al. Effect of nicotine nasal spray on smoking cessation. Arch Intern Med 1994; 154: 2567–72PubMedCrossRefGoogle Scholar
  16. 16.
    Hjalmarson A, Nilsson F, Sjostrom L, et al. The nicotine inhaler in smoking cessation. Arch Int Med 1997; 157(5): 1721–8CrossRefGoogle Scholar
  17. 17.
    Hjalmarson A. Smoking cessation. Evaluation of supportive strategies with special reference to nicotine replacement therapy [thesis]. Goteborg: Goteborg University, 1996Google Scholar
  18. 18.
    Fagerström KO, Säwe U, Tønnesen P. Therapeutic use of nicotine patches: efficacy and safety. J Smok Relat Dis 1992; 3: 247–61Google Scholar
  19. 19.
    Russell MAH, Stableton JA, Feyerabend C, et al. Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. BMJ 1993; 306: 1308–12PubMedCrossRefGoogle Scholar
  20. 20.
    Imperial Cancer Research Fund General Practice Research Group. Effectiveness of a nicotine patch in helping people to stop smoking: results of a randomised trial in general practice. BMJ 1993; 306: 1304–8CrossRefGoogle Scholar
  21. 21.
    McNabb ME, Ebert RV, McCusker K. Plasma nicotine levels produced by chewing nicotine gum. JAMA 1982; 248: 865–8PubMedCrossRefGoogle Scholar
  22. 22.
    McNabb ME. Chewing nicotine gum for 3 months: what happens to plasma nicotine levels?. Can Med Assoc J 1984; 131: 589–92PubMedGoogle Scholar
  23. 23.
    Tønnesen P, Fryd V, Hansen M, et al. Two and four mg nicotine chewing gum and group counseling in smoking cessation: an open, randomized, controlled trial with a 22 month follow-up. Addict Behav 1988; 13: 17–27PubMedCrossRefGoogle Scholar
  24. 24.
    Tønnesen P, Nørregaard J, Mikkelsen K, et al. A double-blind trial of a nicotine inhaler for smoking cessation. JAMA 1993; 269: 1268–71PubMedCrossRefGoogle Scholar
  25. 25.
    Tønnesen P. Smoking cessation programs. In: Hansen HH, editor. Lung cancer. Boston (MA): Kluwer, 1994: 75–89CrossRefGoogle Scholar
  26. 26.
    Sutherland G, Stapleton JA, Russell MAH, et al. Randomised controlled trial of a nasal nicotine spray in smoking cessation. Lancet 1992; 340: 324–9PubMedCrossRefGoogle Scholar
  27. 27.
    Blondal T, Franzon M, Westin A, et al. Controlled trial of nicotine nasal spray with long term follow-up [abstract]. ARRD 1993; 147: A806Google Scholar
  28. 28.
    Taylor CB, Houston-Miller N, Killen JD, et al. Smoking cessation after acute myocardial infarction: effects of a nurse managed intervention. Ann Intern Med 1990; 113(2): 118–23PubMedGoogle Scholar
  29. 29.
    Joseph AM, Norman SM, Ferry LH, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996; 335: 1792–8PubMedCrossRefGoogle Scholar
  30. 30.
    Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease. Nicotine replacement therapy for patients with coronary artery disease. Arch Intern Med 1994; 154: 989–95CrossRefGoogle Scholar
  31. 31.
    Hughes JR. Risk-benefit of nicotine replacement in smoking cessation. Drug Saf 1993; 8(1): 49–56PubMedCrossRefGoogle Scholar
  32. 32.
    Bolinder GM, Ahlborg BO, Lindell JH, et al. Use of smokeless tobacco: blood pressure elevation and other health hazards found in a large-scale population survey. J Intern Med 1992; 232(4): 327–34PubMedCrossRefGoogle Scholar
  33. 33.
    Huhtasaari F, Asplund K, Lundberg V, et al. Tobacco and myocardial infarction: is snuff less dangerous than cigarettes? BMJ 1992; 305(6864): 1252–6PubMedCrossRefGoogle Scholar
  34. 34.
    Mahmarian JJ, Moye LA, Nasser GA, et al. Nicotine patch therapy in smoking cessation reduces the extent of exercise-induced myocardial ischemia. J Am Coll Cardiol 1997; 30: 125–30PubMedCrossRefGoogle Scholar
  35. 35.
    Hwang SL. Heart attacks reported in patch users still smoking.Wall Street Journal 1992 Jun 14Google Scholar
  36. 36.
    U.S. Food and Drug Administration. Transcript of the 23rd Meeting of the U.S. Food and Drug Administration. U.S. Food and Drug Administration, 1992Google Scholar
  37. 37.
    The Health Benefits of Smoking Cessation. Rockville, MD: US Dept of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion, Office on S Smoking and Health; 1990. US Dept of Health and Human Services Publication (CDC) 90-8416Google Scholar
  38. 38.
    Rigotti NA, Eagle KA. Atrial fibrillation while chewing nicotine gum [letter]. JAMA 1986; 225: 1018CrossRefGoogle Scholar
  39. 39.
    Stewart PM, Caterall JR. Chronic nicotine ingestion and atrial fibrillation. Br Heart J 1985; 54; 222–3PubMedCrossRefGoogle Scholar
  40. 40.
    Ottervanger JP, Jeroen MF, de Vries AG. Acute myocardial infarction while using nicotine patch. Chest 1995; 107: 1765–6PubMedCrossRefGoogle Scholar
  41. 41.
    Dacosta A, Guy JM, Tardy B, et al. Myocardial infarction and nicotine patch: a contributing or causative factor? Eur Heart J 1993;14: 1709–11PubMedCrossRefGoogle Scholar
  42. 42.
    Warner JG Jr, Little WC. Myocardial infarction in a patient who smoked while wearing a nicotine patch. Ann Intern Med 1994; 120; 695–6PubMedGoogle Scholar
  43. 43.
    Jorenby DE, Smith SS, Fiore MC, et al. Varying nicotine patch dose and type of smoking counseling. JAMA 1995; 274: 1347–52PubMedCrossRefGoogle Scholar
  44. 44.
    Pierce JR. Stroke following application of a nicotine patch [letter]. DICP 1994; 28; 402Google Scholar
  45. 45.
    Jackson M. Cerebral arterial narrowing with nicotine patch. Lancet 1993; 342; 236–7PubMedCrossRefGoogle Scholar
  46. 46.
    Canadian adverse drugs reaction newsletter. Drugs directorate. Can Med Assoc J 1996 Jan 1; 154(1): 61Google Scholar
  47. 47.
    Ropchan GV, Sanfilippo AJ, Ford SE. Aortic dissection and use of the nicotine patch: a case involving a temporal relationship. Can J Cardiol 1997; 13(5): 525–8PubMedGoogle Scholar
  48. 48.
    Brenner DE, Pethica D, Mickhail HMI, et al. Surveillance of the cardiovascular safety of transdermal nicotine as smoking cessation aid [abstract]. Pharmacoepidemiol Drug Saf 1994; 3 Suppl. 1: 93Google Scholar
  49. 49.
    Aberg A, Bregstrand R, Johansson S, et al. Cessation of smoking after myocardial infarction. Effects on mortality after 10 years. Br Heart J 1983; 49: 416–22Google Scholar
  50. 50.
    Baile WF, Bigelow GE, Gottlieb SH, et al. Rapid resumption of cigarette smoking following myocardial infarction: inverse relation to MI severity. Addict Behav 1982; 7: 373–80PubMedCrossRefGoogle Scholar
  51. 51.
    Daly LE, Mulcahy R, Graham IM, et al. Long term effect on mortality of stopping smoking after unstable angina and myocardial infarction. Br Med J (Clin Res) 1983; 287: 324–6CrossRefGoogle Scholar
  52. 52.
    U.S. Dept of Health and Human Services. The health consequences of smoking: cardiovascular disease. A report of the Surgeon General. Rockville, MD: Dept of Health and Human Services, 1983; DHSS (PHS) no. 84-50204Google Scholar
  53. 53.
    Wilhelmsson C, Vedin JA, Elmfeldt D, et al. Smoking and myocardial infarction. Lancet 1975; I: 415–9CrossRefGoogle Scholar
  54. 54.
    Mulcahy R. Influence of cigarette smoking on morbidity and mortality after myocardial infarction. Br Heart J 1983; 49: 410–5PubMedCrossRefGoogle Scholar
  55. 55.
    Raymond R, Lynch J, Underwood D, et al. Myocardial infarction and normal coronary arteriography: a 10-year clinical and risk analysis of 74 patients. J Am Coll Cardiol 1988; 11: 471–7PubMedCrossRefGoogle Scholar
  56. 56.
    Caralis DG, Ubeydullah D, Kern MJ, et al. Smoking is a risk factor for coronary spasm in young women. Circulation 1992; 85: 905–9PubMedCrossRefGoogle Scholar
  57. 57.
    Peters RW, Brooks M, Todd L. Smoking cessation and arrhythmic death: the CAST experience. J Am Coll Cardiol 1995; 26: 1287–92PubMedCrossRefGoogle Scholar
  58. 58.
    Stein PK, Rottman JN, Kleiger RE. Effect of 21mg transdermal nicotine patches and smoking cessation on heart rate variability. Am J Cardiol 1996; 77(9): 701–5PubMedCrossRefGoogle Scholar
  59. 59.
    Kleiger RE, Miller JP, Moss AJ, et al. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987; 59: 256–62PubMedCrossRefGoogle Scholar
  60. 60.
    Singer DH, Martin GL, Magid N, et al. Low heart rate variability and sudden cardiac death. J Electrocardiol 1988; 21: 46–55CrossRefGoogle Scholar
  61. 61.
    Murray RP, Bailey WC, Daniels K, et al. Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Chest 1996; 109: 438–45PubMedCrossRefGoogle Scholar
  62. 62.
    Barr Taylor C, Huston-Miller N, Killen JD, et al. Smoking cessation after acute myocardial infarction: effects of a nurse-managed intervention. Ann Intern Med 1990; 113(2): 118–23Google Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  • Charlotta Pisinger
    • 1
  • Poul Wennike
    • 1
  • Philip Tønnesen
    • 1
  1. 1.Gentofte University Hospital, Niels AndersensvejHellerupDenmark

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