Skip to main content

Advertisement

SpringerLink
Log in

Cardiovascular Adverse Events Associated with Smoking-Cessation Pharmacotherapies

  • Ischemic Heart Disease (D Mukherjee, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Smoking continues to be the leading cause of preventable deaths in the USA, accounting for one in every five deaths every year, and cardiovascular (CV) disease remains the leading cause of those deaths. Hence, there is increasing awareness to quit smoking among the public and counseling plays an important role in smoking cessation. There are different pharmacological methods to help quit smoking that includes nicotine replacement products available over the counter, including patch, gum, and lozenges, to prescription medications, such as bupropion and varenicline. There have been reports of both nonserious and serious adverse CV events associated with the use of these different pharmacological methods, especially varenicline, which has been gaining media attention recently. Therefore, we systematically reviewed the various pharmacotherapies used in smoking cessation and analyzed the evidence behind these CV events reported with these therapeutic agents.

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.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Centers for Disease Control and Prevention. Health effects of cigarette smoking: fact sheet. 2014. http://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/effects_cig_smoking. Accessed 5 Jul 2014.

  2. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction–executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44:671–719.

    Article  PubMed  Google Scholar 

  3. Jha P, Ramasundarahettige C, Landsman V, Rostron B, Thun M, Anderson RN, et al. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med. 2013;368:341–50.

    Article  CAS  PubMed  Google Scholar 

  4. Wilson K, Gibson N, Willan A, Cook D. Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies. Arch Intern Med. 2000;160:939–44.

    Article  CAS  PubMed  Google Scholar 

  5. Glantz S, Gonzalez M. Effective tobacco control is key to rapid progress in reduction of non-communicable diseases. Lancet. 2012;379:1269–71.

    Article  PubMed Central  PubMed  Google Scholar 

  6. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General: Office on Smoking and Health. Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion; 2006.

  7. Fiore M, Jaen CR, Baker TB, Bailey WC, Bennett G, Benowitz NL, et al. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. public health service report. Clinical practice guideline treating tobacco use and dependence 2008 update panel, liaisons and staff. Am J Prev Med. 2008;35:158–76.

    Article  Google Scholar 

  8. Hartmann-Boyce J, Stead LF, Cahill K, Lancaster T. Efficacy of interventions to combat tobacco addiction: Cochrane update of 2012 reviews. Addiction. 2013;108:1711–21.

    Article  PubMed  Google Scholar 

  9. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. The Cochrane database of systematic reviews. Cochrane Database Syst Rev. 2013;5:CD009329. This large overview/meta-analysis confirmed the efficacy of all three smoking cessation pharmacotherapies versus placebo and versus each other as quitting aids and demonstrated no significant excess of cardiovascular events in users of all three treatments.

  10. Glover ED, Glover PN, Payne TJ. Treating nicotine dependence. Am J Med Sci. 2003;326:183–6.

    Article  PubMed  Google Scholar 

  11. Fiore MC, Smith SS, Jorenby DE, Baker TB. The effectiveness of the nicotine patch for smoking cessation. A meta-analysis. JAMA. 1994;271:1940–7.

    Article  CAS  PubMed  Google Scholar 

  12. US Department of Health and Human Services, Public Health Services, Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence: clinical practice guideline. Rockville: US Dept of Health and Human Services, Public Health Service; 2000. p. 25–90.

    Google Scholar 

  13. Blann AD, Steele C, McCollum CN. The influence of smoking and of oral and transdermal nicotine on blood pressure, and haematology and coagulation indices. Thromb Haemost. 1997;78:1093–6.

    CAS  PubMed  Google Scholar 

  14. Lucini D, Bertocchi F, Malliani A, Pagani M. Autonomic effects of nicotine patch administration in habitual cigarette smokers: a double-blind, placebo-controlled study using spectral analysis of RR interval and systolic arterial pressure variabilities. J Cardiovasc Pharmacol. 1998;31:714–20.

    Article  CAS  PubMed  Google Scholar 

  15. Zevin S, Jacob 3rd P, Benowitz NL. Dose-related cardiovascular and endocrine effects of transdermal nicotine. Clin Pharmacol Ther. 1998;64:87–95.

    Article  CAS  PubMed  Google Scholar 

  16. Mundal HH, Hjemdahl P, Gjesdal K. Acute effects of low dose nicotine gum on platelet function in non-smoking hypertensive and normotensive men. Eur J Clin Pharmacol. 1995;47:411–6.

    Article  CAS  PubMed  Google Scholar 

  17. Benowitz NL, Fitzgerald GA, Wilson M, Zhang Q. Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking. J Am Coll Cardiol. 1993;22:1159–67.

    Article  CAS  PubMed  Google Scholar 

  18. Tzivoni D, Keren A, Meyler S, Khoury Z, Lerer T, Brunel P. Cardiovascular safety of transdermal nicotine patches in patients with coronary artery disease who try to quit smoking. Cardiovasc Drugs Ther. 1998;12:239–44.

    Article  CAS  PubMed  Google Scholar 

  19. Keeley EC, Pirwitz MJ, Landau C, Lange RA, Hillis LD, Foerster EH, et al. Intranasal nicotine spray does not augment the adverse effects of cigarette smoking on myocardial oxygen demand or coronary arterial dimensions. Am J Med. 1996;101:357–63.

    Article  CAS  PubMed  Google Scholar 

  20. Nitenberg A, Antony I. Effects of nicotine gum on coronary vasomotor responses during sympathetic stimulation in patients with coronary artery stenosis. J Cardiovasc Pharmacol. 1999;34:694–9.

    Article  CAS  PubMed  Google Scholar 

  21. Mall T, Grossenbacher M, Perruchoud AP, Ritz R. Influence of moderately elevated levels of carboxyhemoglobin on the course of acute ischemic heart disease. Respiration. 1985;48:237–44.

    Article  CAS  PubMed  Google Scholar 

  22. Palmer KJ, Buckley MM, Faulds D. Transdermal nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. Drugs. 1992;44:498–529.

    Article  CAS  PubMed  Google Scholar 

  23. Mahmarian JJ, Moye LA, Nasser GA, Nagueh SF, Bloom MF, Benowitz NL, et al. Nicotine patch therapy in smoking cessation reduces the extent of exercise-induced myocardial ischemia. J Am Coll Cardiol. 1997;30:125–30.

    Article  CAS  PubMed  Google Scholar 

  24. Ford CL, Zlabek JA. Nicotine replacement therapy and cardiovascular disease. Mayo Clin Proc. 2005;80:652–6.

    Article  CAS  PubMed  Google Scholar 

  25. Ottervanger JP, Festen JM, de Vries AG, Stricker BH. Acute myocardial infarction while using the nicotine patch. Chest. 1995;107:1765–6.

    Article  CAS  PubMed  Google Scholar 

  26. Ropchan GV, Sanfilippo AJ, Ford SE. Aortic dissection and use of the nicotine patch: a case involving a temporal relationship. Can J Cardiol. 1997;13:525–8.

    CAS  PubMed  Google Scholar 

  27. Van der Klauw MM, Van Hillo B, Van den Berg WH, Bolsius EP, Sutorius FF, Stricker BH. Vasculitis attributed to the nicotine patch (Nicotinell). Br J Dermatol. 1996;134:361–4.

    Article  PubMed  Google Scholar 

  28. Dacosta A, Guy JM, Tardy B, Gonthier R, Denis L, Lamaud M, et al. Myocardial infarction and nicotine patch: a contributing or causative factor? Eur Heart J. 1993;14:1709–11.

    Article  CAS  PubMed  Google Scholar 

  29. Pierce Jr JR. Stroke following application of a nicotine patch. Ann Pharmacother. 1994;28:402.

    PubMed  Google Scholar 

  30. Warner Jr JG, Little WC. Myocardial infarction in a patient who smoked while wearing a nicotine patch. Ann Intern Med. 1994;120:695.

    Article  PubMed  Google Scholar 

  31. Riche G, Nighoghossian N, Trouillas P. Intracerebral haematoma after application of nicotine patch. Lancet. 1995;346:777–8.

    Article  CAS  PubMed  Google Scholar 

  32. Mathew TP, Herity NA. Acute myocardial infarction soon after nicotine replacement therapy. QJM. 2001;94:503–4.

    Article  CAS  PubMed  Google Scholar 

  33. 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;154:989–95.

  34. Joseph AM, Norman SM, Ferry LH, Prochazka AV, Westman EC, Steele BG, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med. 1996;335:1792–8.

    Article  CAS  PubMed  Google Scholar 

  35. Mills EJ, Wu P, Lockhart I, Wilson K, Ebbert JO. Adverse events associated with nicotine replacement therapy (NRT) for smoking cessation. A systematic review and meta-analysis of one hundred and twenty studies involving 177,390 individuals. Tob Induc Dis. 2010;8:8.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Haustein KO, Krause J, Haustein H, Rasmussen T, Cort N. Comparison of the effects of combined nicotine replacement therapy vs. cigarette smoking in males. Nicotine Tob Res. 2003;5:195–203.

    Article  CAS  PubMed  Google Scholar 

  37. Greenland S, Satterfield MH, Lanes SF. A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch. Drug Saf. 1998;18:297–308.

    Article  CAS  PubMed  Google Scholar 

  38. Kimmel SE, Berlin JA, Miles C, Jaskowiak J, Carson JL, Strom BL. Risk of acute first myocardial infarction and use of nicotine patches in a general population. J Am Coll Cardiol. 2001;37:1297–302.

    Article  CAS  PubMed  Google Scholar 

  39. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Rockville, MD: Department of Health and Human Services, Public Health Service, Office of Surgeon General; 2010.

  40. Mills EJ, Thorlund K, Eapen S, Wu P, Prochaska JJ. Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis. Circulation. 2014;129:28–41. This was a major large meta-analysis of electronic databases, RCTs, and US FDA reports, which showed that smoking cessation therapies do not appear to raise the risk of serious cardiovascular disease events, except for use in smokers hospitalized for ST-segment-elevation myocardial infarction, which needs further study.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Gourlay SG, Forbes A, Marriner T, McNeil JJ. Predictors and timing of adverse experiences during trandsdermal nicotine therapy. Drug Saf. 1999;20:545–55.

    Article  CAS  PubMed  Google Scholar 

  42. Rigotti NA, Thorndike AN, Regan S, McKool K, Pasternak RC, Chang Y, et al. Bupropion for smokers hospitalized with acute cardiovascular disease. Am J Med. 2006;119:1080–7.

    Article  CAS  PubMed  Google Scholar 

  43. Tonstad S, Farsang C, Klaene G, Lewis K, Manolis A, Perruchoud AP, et al. Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study. Eur Heart J. 2003;24:946–55.

    Article  CAS  PubMed  Google Scholar 

  44. Roose SP. Considerations for the use of antidepressants in patients with cardiovascular disease. Am Heart J. 2000;140(4 Suppl):84–8.

    Article  CAS  PubMed  Google Scholar 

  45. Roose SP, Dalack GW, Glassman AH, Woodring S, Walsh BT, Giardina EG. Cardiovascular effects of bupropion in depressed patients with heart disease. Am J Psychiatry. 1991;148:512–6.

    Article  CAS  PubMed  Google Scholar 

  46. Beyens MN, Guy C, Mounier G, Laporte S, Ollagnier M. Serious adverse reactions of bupropion for smoking cessation: analysis of the French Pharmacovigilance Database from 2001 to 2004. Drug Saf. 2008;31:1017–26.

    Article  CAS  PubMed  Google Scholar 

  47. Issa JS, Perez GH, Diament J, Zavattieri AG, de Oliveira KU. Effectiveness of sustained-release bupropion in the treatment of smoker patients with cardiovascular disease. Arq Bras Cardiol. 2007;88:434–40.

    Article  CAS  PubMed  Google Scholar 

  48. Perkins KA. Smoking cessation in women. Special considerations. CNS Drugs. 2001;15:391–411.

    Article  CAS  PubMed  Google Scholar 

  49. Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA, et al. Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology. 2007;52:985–94.

    Article  CAS  PubMed  Google Scholar 

  50. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2011;16, CD006103.

    Google Scholar 

  51. Ari H, Celiloglu N, Ari S, Cosar S, Doganay K, Bozat T. The effect of varenicline on heart rate variability in healthy smokers and nonsmokers. Auton Neurosci. 2011;164:82–6.

    Article  CAS  PubMed  Google Scholar 

  52. Wang J, Wang X, Irnaten M, Venkatesan P, Evans C, Baxi S, et al. Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons. J Neurophysiol. 2003;89:2473–81.

    Article  CAS  PubMed  Google Scholar 

  53. Benowitz NL. Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment. Prog Cardiovasc Dis. 2003;46:91–111.

    Article  CAS  PubMed  Google Scholar 

  54. Singh S, Loke YK, Spangler JG, Furberg CD. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ. 2011;183:1359–66.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Prochaska JJ, Hilton JF. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ. 2012;344:e2856.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Harrison-Woolrych M, Maggo S, Tan M, Savage R, Ashton J. Cardiovascular events in patients taking varenicline: a case series from intensive postmarketing surveillance in New Zealand. Drug Saf. 2012;35:33–43.

    Article  CAS  PubMed  Google Scholar 

  57. Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, Tonstad S. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation. 2010;121:221–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. FDA Drug Safety Communication. Chantix (varenicline) may increase the risk of certain cardiovascular adverse events in patients with cardiovascular disease Issued 22 July 2011. http://www.fda.gov/Drugs/Drugsafety/ucm259161.htm. Accessed 5 Jul 2014.

  59. US Food and Drug Administration. FDA drug safety communication: safety review update of Chantix (Varenicline) and risk of cardiovascular adverse events. http://www.fda.gov/drugs/drugsafety/ucm330367.htm. Accessed 5 Jul 2014.

  60. Toh S, Baker MA, Brown JS, Kornegay C, Platt R, Mini-Sentinel I. Rapid assessment of cardiovascular risk among users of smoking cessation drugs within the US Food and Drug Administration’s Mini-Sentinel program. JAMA Intern Med. 2013;173:817–9. This was a recent FDA mini-sentinel evaluation of CVD events that found no difference in CVD event risk between varenicline and bupropion users.

    Article  CAS  PubMed  Google Scholar 

  61. Svanstrom H, Pasternak B, Hviid A. Use of varenicline for smoking cessation and risk of serious cardiovascular events: nationwide cohort study. BMJ. 2012;345:e7176. This was a large, nationwide, observational cohort study that found no increased risk of major cardiovascular events associated with the use of varenicline compared with bupropion for smoking cessation.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Hajek P, McRobbie H, Myers K. Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis. Thorax. 2013;68(11):1037–42.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Ondrej Sochor was supported by the European Regional Development Fund—Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123) and by a grant awarded by the Ministry of Health of the Czech Republic (NT13434-4/2012).

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

None of the authors have any conflicts of interest in connection with this work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, State University of New York Downstate Medical Center, Brooklyn, NY, USA

    Abhishek Sharma

  2. Department of Cardiovascular Medicine, Maimonides Medical Center, Brooklyn, NY, USA

    Saurabh Thakar

  3. Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, USA

    Carl J. Lavie

  4. Department of Preventive Medicine, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    Carl J. Lavie

  5. Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY, USA

    Jalaj Garg

  6. Department of Internal Medicine, Mount Sinai Englewood Hospital and Medical Center Englewood, Englewood, NJ, USA

    Parasuram Krishnamoorthy

  7. Division of Cardiology, Mayo College of Medicine, Rochester, MN, USA

    Ondrej Sochor

  8. International Clinical Research Center - Department of Cardiovascular Diseases, St. Anne’s University Hospital Brno, Brno, Czech Republic

    Ondrej Sochor

  9. Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Armin Arbab-Zadeh

  10. Department of Medicine, Maimonides Medical Center, Brooklyn, NY, USA

    Edgar Lichstein

  11. Brooklyn, NY, USA

    Abhishek Sharma

Authors
  1. Abhishek Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saurabh Thakar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carl J. Lavie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jalaj Garg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Parasuram Krishnamoorthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ondrej Sochor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Armin Arbab-Zadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Edgar Lichstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abhishek Sharma.

Additional information

This article is part of the Topical Collection on Ischemic Heart Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharma, A., Thakar, S., Lavie, C.J. et al. Cardiovascular Adverse Events Associated with Smoking-Cessation Pharmacotherapies. Curr Cardiol Rep 17, 554 (2015). https://doi.org/10.1007/s11886-014-0554-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-014-0554-8

Keywords

Search

Navigation