Smokers making a quit attempt using e-cigarettes with or without nicotine or prescription nicotine replacement therapy: Impact on cardiovascular function (ISME-NRT) - a study protocol

Markos Klonizakis, Helen Crank, Anil Gumber, Leonie S Brose, Markos Klonizakis, Helen Crank, Anil Gumber, Leonie S Brose

Abstract

Background: The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or "e-") cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers.

Methods: This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately) combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants' "quit date".

Discussion: Participants will be assessed at baseline, 3 days following their self-determined "quit date", at intervention end (3 months) and 6 months following their "quite date". Findings are expected to give an indication of the cardiovascular effects of e-cigarettes both in the short- and in the medium-term period, informing the general public, policy holders and researchers, helping to define the future role of e-cigarettes as a smoking cessation aid.

Trial registration: Clinicaltrials.gov NCT03061253 . Registered 17th February 2017.

Keywords: E-cigarettes; FMD; LDF; Macrocirculation; Microcirculation; Nicotine Replacement Therapy.

Figures

Fig. 1
Fig. 1
Participant study schedule

References

    1. The World Health Report 2003: Shaping the Future. World Health Organization; 2003. . Accessed Feb 2017.
    1. Gaemperli O, Liga R, Bhamra-Ariza P, Rimoldi O. Nicotine addiction and coronary artery disease: impact of cessation interventions. Curr Pharm Des. 2010;16(23):2586–2597. doi: 10.2174/138161210792062894.
    1. Mallaina P, Lionis C, Rol H, Imperiali R, Burgess A, Nixon M, Malvestiti FM. Smoking cessation and the risk of cardiovascular disease outcomes predicted from established risk scores: results of the cardiovascular risk assessment among smokers in primary Care in Europe (CV-ASPIRE) study. BMC Public Health. 2013;13:362. doi: 10.1186/1471-2458-13-362.
    1. Mensah GA. Healthy endothelium: the scientific basis for cardiovascular health promotion and chronic disease prevention. Vasc Pharmacol. 2007;46(5):310–314. doi: 10.1016/j.vph.2006.10.013.
    1. O’Grady HL, Leahy A, McCormick PH, Fitzgerald P, Kelly CK, Bouchier-Hayes DJ. Oral folic acid improves endothelial dysfunction in cigarette smokers. J Surg Res. 2002;106(2):342–345. doi: 10.1006/jsre.2002.6467.
    1. Csordas A, Bernhard D. The biology behind the atherothrombotic effects of cigarette smoke. Nat Rev Cardiol. 2013;10(4):219–230. doi: 10.1038/nrcardio.2013.8.
    1. Coleman T, Agboola S, Leonardi-Bee J, Taylor M, McEwen A, McNeill A. Relapse prevention in UK stop smoking services: current practice, systematic reviews of effectiveness and cost-effectiveness analysis. Health Technol Assess. 2010;14(49):1–152. doi: 10.3310/hta14490.
    1. Royal College of Physicians . Nicotine addiction in Britain. A report of the tobacco advisory Group of the Royal College of physicians. London: RCP; 2000.
    1. Health and Social Care Information Centre Statistics on NHS Stop Smoking Services in England - April 2016 to September 2016. . Accessed Feb 2017.
    1. Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends Cardiovasc Med. 2016;26(6):515-23.
    1. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013;5:CD009329.
    1. Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014;34(3):509–515. doi: 10.1161/ATVBAHA.113.300156.
    1. McNeill A, Brose LS, Calder R, Hitchman SC. E-cigarettes: an evidence update report commissioned by Public Health England. . Accessed Feb 2017.
    1. Smoking in England. . Accessed Feb 2017.
    1. Hartmann-Boyce J, McRobbie H, Bullen C, Begh R, Stead LF, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2016;9:CD010216.
    1. Carnevale R, Sciarretta S, Violi F, Nocella C, Loffredo L, Perri L, Peruzzi M, Marullo AG, De Falco E, Chimenti I, Valenti V, Biondi-Zoccai G, Frati G. Acute impact of tobacco vs electronic cigarette smoking on oxidative stress and vascular function. Chest. 2016;150(3):606–612. doi: 10.1016/j.chest.2016.04.012.
    1. Library of the European Parliament. Electronic cigarettes. . Accessed Feb 2017.
    1. BMA. Why are we concerned about e-cigarettes? . Accessed Feb 2017.
    1. Bullen C, Howe C, Laugesen M, McRobbie H, Parag V, Williman J, Walker N. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382(9905):1629-37.
    1. Manzoli L, La Vecchia C, Flacco ME, Capasso L, Simonetti V, Boccia S, Di Baldassarre A, Villari P, Mezzetti A, Cicolini G. Multicentric cohort study on the long-term efficacy and safety of electronic cigarettes: study design and methodology. BMC Public Health. 2013;13(1):883. doi: 10.1186/1471-2458-13-883.
    1. Leone A, Landini L. Vascular pathology from smoking: look at the microcirculation! Curr Vasc Pharmacol. 2013;11(4):524–530. doi: 10.2174/1570161111311040016.
    1. Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Tschakovsky ME, Green DJ. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011;300(1):H2–12. doi: 10.1152/ajpheart.00471.2010.
    1. National Centre for Smoking Cessation and Training. Standard Treatment Programme: A guide to providing behavioural support for smoking cessation. . Accessed Feb 2017.
    1. Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO. The Fagerström test for nicotine dependence: a revision of the Fagerström tolerance questionnaire. Br J Addict. 1991;86:1119–1127. doi: 10.1111/j.1360-0443.1991.tb01879.x.
    1. Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20(10):1727–1736. doi: 10.1007/s11136-011-9903-x.
    1. Collins GS, Altman DG. An independent external validation and evaluation of QRISK cardiovascular risk prediction: a prospective open cohort study. BMJ. 2009;339:b2584. doi: 10.1136/bmj.b2584.
    1. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–1395. doi: 10.1249/01.MSS.0000078924.61453.FB.
    1. Klonizakis M, Winter E. Effects of arm-cranking exercise in cutaneous microcirculation in older, sedentary people. Microvasc Res. 2011;81(3):331–336. doi: 10.1016/j.mvr.2011.01.008.
    1. Maeda K, Noguchi Y, Fukui T. The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis. Prev Med. 2003;37(4):283–290. doi: 10.1016/S0091-7435(03)00110-5.
    1. West R, Hajek P, Stead L, Stapleton J. Outcome criteria in smoking cessation trials: proposal for a common standard. Addiction. 2005;100(3):299–303. doi: 10.1111/j.1360-0443.2004.00995.x.
    1. Tew GA, Michaels J, Crank H, Middleton G, Gumber A, Klonizakis M. Supervised exercise training as an adjunctive therapy for venous leg ulcers: study protocol for a randomised controlled trial. Trials. 2015;16:443. doi: 10.1186/s13063-015-0963-z.
    1. Forey BA, Fry JS, Lee PN, Thornton AJ, Coombs KJ. The effect of quitting smoking on HDL-cholesterol - a review based on within-subject changes. Biomark Res. 2013;1(1):26. doi: 10.1186/2050-7771-1-26.
    1. Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin J, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleža-Jerić K, Laupacis A, Moher D. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.
    1. Ritchie J, Lewis J. Qualitative research practice: a guide for social Science students and researchers. London, UK: Sage; 2003.
    1. Pope C, Ziebland S, Mays N. Qualitative research in health care. Analysing qualitative data. BMJ. 2000;320(7227):114–116. doi: 10.1136/bmj.320.7227.114.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever