George 2019.

Study characteristics
Methods	Design: Prospective, randomized controlled trial with a parallel, nonrandomized preference cohort Recruitment: Participants were recruited from local advertisements, smoking cessation databases, and visits to local businesses, as well as via the Scottish Primary Care Research Network Setting: Single tertiary research centre, UK Study start date: August 2016; Study end date: July 2018
Participants	Total N: 114 in “final evaluable dataset” (145 recruited into the trial) N per arm: Tobacco cigarettes (TC): 40; EC nicotine (16 mg): 37; EC‐Nicotine‐free: 37 Inclusion criteria: People who smoke ≥ 18 years of age who had smoked ≥ 15 cigarettes/day for at least 2 years were free from established CV disease, diabetes, and chronic kidney disease; and were not on medication for those conditions Willing to stop tobacco cigarettes for period of study if required Willing not to use electronic cigarettes if required Able to give informed consent Exclusion criteria: Pregnant or lactating Women of childbearing potential who do not abstain from sex or use effective contraception On current prescribed medication for cardiovascular disease History of cardiovascular disease (excluding hypertension), diabetes, active malignance or chronic renal disease Nut allergy Participation in another clinical trial (other than observational trials and registries) with an investigational product and/or intervention within 30 days before visit 1 65.4% women; mean age 46.9; mean cpd 18.7 Motivated to quit: TC group: No; EC nicotine (16 mg): Yes; EC‐Nicotine‐free: Yes.
Interventions	EC: Cig‐a‐like EC nicotine (16 mg) arm: EC containing 16 mg nicotine (Vapourlites Starter Kit with XR5 16 mg nicotine cartomizer; Vapourlites, Peterlee, United Kingdom) EC‐Nicotine‐free arm: Nicotine‐free EC plus nicotine flavoring (Vapourlites Starter Kit with 0 mg nicotine cartomizer) (non‐randomized) TC arm: continued their usual daily smoking habits and did not use EC for the 4‐week period of the trial
Outcomes	Week 4 Adverse events and biomarkers: BP, heart rate, adverse events Other outcomes measured: Endothelial function, oxidized low‐density lipoprotein, high‐sensitivity C‐reactive protein, tissue plasminogen activator, and platelet activation inhibitor‐1
Study funding	"The VESUVIUS (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use) trial was funded by the British Heart Foundation (grant PG/15/64/31681); and supported by Immunoassay Biomarker Core Laboratory, University of Dundee, the Tayside Medical Sciences Centre, and the NHS Tayside Smoking Cessation Service. The funder had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or in the decision to submit for publication."
Author declarations	"Dr. Donnan has received research grants from AbbVie, Shire, and Gilead Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose."
Notes	New for 2020 update
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Consented participants who were willing to quit smoking were randomized to one of the EC arms in a 1:1 fashion using a centrally controlled web‐based good clinical practices– compliant randomization system to either: 1) EC containing 16 mg nicotine; or 2) nicotine‐free EC plus nicotine flavoring because it was considered by the institutional ethics committee as ethically unacceptable to randomize those who were willing to quit smoking into a smoking arm. Those unwilling to consider quitting smoking continued in the parallel preference TC cohort
Allocation concealment (selection bias)	Low risk	Central randomization
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not specified
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not blinded and AE/SAE data are self‐report only. For other outcomes, low risk as objectively measured: Quote: “Patients fasted overnight and measurements were conducted at baseline and 1 month according to the International Brachial Artery Reactivity Task Force guidelines (19) by a single operator (M.H.) blinded to study allocation at a single site.” “Pulse wave velocity and augmentation index were measured at baseline and 1 month by a single operator (M.H.) blinded to study allocation.”
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Number randomized not provided per group. Quote: “A total of 145 patients were recruited into the trial (Figure 2). A final number of 114 patients (40 TC, 37 EC‐nicotine, 37 EC‐nicotine‐free) completed both visits.”
Selective reporting (reporting bias)	Low risk	Clinical trial record lists: Change in FMD; Change in oxidized LDL; Change in PAI‐1; Change in hs‐CRP; Change in Pulse Wave Velocity; Change in tPA; Change in Augmentation Index@75bpm All reported in the paper