Study ID	Withdrawals due to treatment	Cardiovascular adverse events (AEs)	Serious adverse events (SAEs)	Notes
Abdullah 2013	Not reported	Not reported	Not reported	No AE data reported
Baker 2016	Not reported	Not reported	0/421 combination group; 0/241 patch group.	AEs measured for duration of treatment (12 weeks). Only most common AEs reported (i.e. in > 5% of participants).
Berlin 2011	Not reported	Standard care: Chest pain: 7/155; Palpitations: 2/155;   Dose adaptation: Chest pain: 5/155; Palpitations: 5/155	12/155 Standard care;  9/155 Dose adaptation	AEs measured for duration of study.
Blondal 1999	Not reported	Not reported	Not reported	AEs measured during treatment (at 3 months). Not reported in detail by relevant trial arms.
Bohadana 2000	Not reported	Not reported	1/200 intervention group; 1/200 control group. Both unrelated to treatment.	AEs measured at 1 year. Treatment was for 6 months. Only most common AEs reported.
Bolin 1999	Not reported	Not reported	Not reported	No AEs data reported
Bolliger 2007	Not reported	Not reported	Not reported	AEs measured at each visit to 1 year. Treatment was for 12 weeks. Only most common AEs reported (i.e. in > 5% of participants)
Bullen 2010	Not reported	Cardiac: 10/549 (1.8%) pre‐cessation group; 8/551 (1.5%) control group   Unspecified chest pain: 9/549 pre‐cessation group; 1/551 control group	Number of participants: 11/549 intervention group; 7/551 control group. Total number of events: 99/549 intervention group; 109/551 control group.	AEs measured at all contacts (6 months). Cardiac AEs numerator is number of people experiencing AEs.
Burns 2016	Not reported	Not reported	Not reported	No AEs data reported
Caldwell 2014	Not reported	Not reported	Not reported	AEs measured at 1 year. Treatment was for 6 months.
Caldwell 2016	15/246 (6.1%) nicotine patch plus inhaler; 3/256 (1.2%) nicotine patch plus placebo inhaler	Chest discomfort: baseline, active 3/246 vs control 1/256. One day quit, active 1/224 vs control 0/234. 1 month quit, active 2/170 vs control 0/179. 3 months quit, active 4/147 vs control 0/143. 6 months quit, active 0/128 vs control 0/119.   Palpitations: baseline, active 3/246 vs control 0/256. 1 day quit, active 6/224 vs control 4/234. 1 month quit, active 4/170 vs control 2/179. 3 months quit, active 1/147 vs control 2/143. 6 months quit, active 2/128 vs control 0/119	5/246 nicotine patch and inhaler group; 0/256 nicotine patch and placebo group.	AEs measured during treatment (6 months)
CEASE 1999	72 (2%) overall. Not reported by relevant trial arm.	Palpitations and tachycardia: 32/1430 (2.3%) 25 mg group; 37/1431 (2.6%) 15 mg group	Do not report all SAEs. Not reported by length of treatment. Myocardial infarction 1/1430 25 mg group; 2/1431 15 mg group.	AEs during treatment (8 weeks). SAEs measured during whole study period. Not reported in detail by relevant trial arms.
Cooney 2009	0% overall.	Cardiac (related to treatment): 0/45 (0%) nicotine patch and active gum group; 0/51 (0%) nicotine patch and placebo gum group.	Not reported	AEs measured during treatment (6 months).
Croghan 2003	4/459 (0.9%) patch group; 14/463 (3%) spray group; 2/462 (0.4%) combined group.	Not reported	Not reported	AEs measured to 6 months. Treatment was for 6 weeks. Only most common AEs reported. "No other AEs were reported with a great deal of frequency"
Cummings 2011	Not reported	Not reported	Not reported	No AE data reported
Dale 1995	1/18 (5.6%) 44 mg group; 0/17 (0%) 22 mg group.	Not reported	Not reported	AEs (nicotine toxicity only, not including cardiac) measured during first week of treatment (inpatient phase). Treatment continued for 6 weeks
Daughton 1991	2 (1.3%) participants overall. Not reported by trial arm.	Not reported	Not reported	AEs measured weekly during treatment (4 weeks). Only most common AEs reported (i.e. in > 5% of participants)
Dennis 2016	Not reported	Not reported	Not reported	No AE data reported
Dignan 2019	Not reported	Not reported	Not reported	No AE data reported
Garvey 2000	2/203 4 mg gum group; 1/202 2 mg gum group	Not reported	Not reported	AEs not reported in detail by relevant trial arms.
Garvey 2006	Not reported	Not reported	Not reported	No AE data reported
Glavas 2003	1/40 3‐week group (additional person withdrew as perceived treatment as ineffective); 2/40 6‐week group	Cardiac: 0/40 (0%) 3‐week group; 0/40 (0%) 6‐week group	0/40 intervention group; 0/40 control group.	AEs measured during treatment (3 weeks or 6 weeks depending on treatment group)
Goldstein 1989	Not reported	Not reported	Not reported	No AE data reported
Hall 2009	Not reported	Midsternal pressure: 1/203 (0.5%) extended (50 week) NRT group; 0/199 (0%) in brief (10 week) NRT group	9/203 extended (50 week) NRT group; 4/199 brief (10 week) NRT group. CARDIAC SAEs: 4/203 extended (50 week) NRT group; 0/199 brief (10 week) NRT group.	AEs measured to week 104. Treatment was to week 50.
Hays 1999	Not reported	Cardiovascular (angina pectoris, cardiovascular disorder, chest pain, and/or myocardial infarction): 5/321 (1.6%) free patches group; 9/315 (2.9%) pay for patches group	SAEs not fully reported. 5 cardiovascular SAEs in trial (2 myocardial infarction: 1 in known NRT arm, 1 in placebo arm) (not used in this review).	AEs measured during treatment (6 weeks)
Herrera 1995	Not reported	Not reported	Not reported	Adverse effects measured daily during treatment. Tachycardia was observed. Not reported in detail by relevant trial arms.
Hilleman 1994	7/69 (10%) fixed dose; 8/71 (11%) tapered dose	Not reported	Not reported	Some AE data reported. Time measured not reported.
Hughes 1990	Not reported	Not reported	Not reported	AEs (not including cardiac) measured during treatment (at 1 week).
Hughes 1991	Not reported	Not reported	Not reported	No AE data reported
Hughes 1999	3/260 (1%) 21 mg group; 8/260 (3%) 35 mg group; 16/259 (6%) 42 mg group	Cardiac (mostly tachycardia, vasodilation, and palpitation): 8% of 42 mg group, not reported for other groups	3/259 42 mg group; 1/260 35 mg group; 1/260 21 mg group	Withdrawals in first 4 months. AEs measured to 6 or 12 months depending on site. Treatment was for 16 weeks. AEs not reported in detail by relevant trial arms
Hughes 2018	9% overall. Not reported by trial arm	Not reported	4/356 continue patch group; 4/345 discontinue patch group. 1 SAE in each group was cardiac‐related.	AEs measured to 1 week post treatment (12 weeks). Only most common AEs reported
Jorenby 1995	Not reported	Not reported	4/252 44 mg intervention group (2 cardiovascular: stroke and myocardial infarction); 0/252 control group	AEs measured weekly during treatment (8 weeks). Only most common AEs reported
Kalman 2006	Not reported	Not reported	Not reported	AEs measured during treatment (up to 12 weeks post‐quit)
Killen 1990	21/152 (13.7%) ad lib group; 16/147 (12.5%) fixed group	Not reported	Not reported	AEs measured weekly during treatment (8 weeks). Only most common AEs reported (10 most common)
Killen 1999	Not reported	Irregular heartbeat: 21/206 (10%) 25 mg group; 20/202 (10%) 15 mg group   Severe irregular heartbeat: 5/206 (2.4%) 25 mg group; 6/202 (3%) 15 mg group	Not reported	AEs self‐reported by participants. Measured during treatment (to 6 weeks)
Kornitzer 1987	Not reported	Not reported	Not reported	No AE data reported
Kornitzer 1995	1/149 (0.7%) nicotine patch and gum group; 2/150 (1.3%) nicotine patch and placebo gum group	Not reported	Not reported	AEs measured at each visit during treatment (6 months). Not reported in detail by relevant trial arms
Krupski 2016	Not reported	Not reported	Not reported	No AE data reported
Kupecz 1996	0/21 (0%) patch group; 4/17 (23%) gum group	Cardiac: 0/21 (0%) patch group; 0/17 (0%) gum group	0/21 patch group; 0/17 gum group	AEs measured at each session to 1 year. Treatment was for 24 weeks. AEs presented here measured at 6 weeks (during treatment)
LeBlanc 2017	Not reported	Not reported	Not reported	No AEs data reported
Lerman 2004	Not reported	Not reported	0/175 patch group; 0/175 spray group	AEs measured in counselling sessions during treatment (8 weeks)
Leung 2019	Not reported	Palpitations: 3/286 single therapy (nicotine patch); 0/274 combined NRT group	Not reported	Single NRT group: 14 withdrawn from study due to refusal, side effects, geographical reason, and death from cancer. Combined NRT group: 7 withdrawn from study due to refusal, geographical reason and death from cancer. In the single NRT group, 12 (4.2%) reported side effects from nicotine patch. In the combined NRT group, 7 (2.6%) reported side effects from NRT. There was no significant difference between the two groups (P = 0.315).
Moolchan 2005	Not reported	Not reported	Not reported	AEs measured during treatment (12 weeks). Only most common AEs reported (19 most common)
Paoletti 1996	Not reported	Not reported	Not reported	AEs measured at visits. Participants were asked about particular symptoms but none cardiac. Paper states, "Heart rate and blood pressure were not affected by the different treatments."
Piper 2009	0/260 (0%) lozenge group; 0/262 (0%) patch and lozenge group	Not reported	32 SAEs in 6 months. Not reported by trial arm	AEs measured at visits during treatment (8 weeks). No SAEs were possibly related to treatment and no withdrawals due to AEs in relevant trial arms.
Piper 2016	Not reported	Not reported	0 SAEs in any group. 0 cardiac SAEs in any group.	AEs measured to 26 weeks. Not reported in detail by relevant trial arms
Puska 1995	Not reported	Not reported	Not reported	AEs measured at all visits during treatment (52 weeks). Only moderate or severe AEs reported
Rey 2009	2 (4%) participants overall. Not reported by trial arm	Not reported	Not reported	No AE data reported
Rose 1994	Not reported	Not reported	Not reported	AEs measured until 1 week after treatment. Only AEs relating to mecamylamine treatment discussed
Rose 1998	0/40 (0%) preloading group; 1/40 (2.5%) no preloading group	Not reported	Not reported	AEs measured during preloading period. 5 people withdrew for reasons unrelated to treatment.
Rose 2006	Not reported	Not reported	Not reported	No AE data reported
Rose 2009	Not reported	Not reported	1/191 preloading nicotine patch group; 3/188 preloading placebo patch group	Timing of AEs measurements not reported. AEs only reported if self‐reported severity was moderate or greater
Rose 2010	3% overall. Not reported by trial arm.	Not reported	Not reported	AEs measured during treatment (12 weeks). Not reported in detail by relevant trial arms
Schlam 2016	Not reported	Not reported	10/275 26‐week patch group; 6/269 8‐week patch group. CARDIAC SAEs: 4/275 26‐week patch group; 5/269 8‐week patch group	AEs measured to 1 year. Treatment was for 8 or 26 weeks. Only most common AEs reported. SAE data from clinicaltrials.gov. Paper states no SAE in trial
Schnoll 2010a	1/282 (0.4%) extended treatment group; 0/282 (0%) standard treatment group	Pounding heart: Week 1: 2/247 (0.8%) extended group; 3/252 (1.2%) standard group. Week 12: 0/182 (0%) extended group; 2/134 (1.5%) standard group.	3/282 extended NRT group (including 1 myocardial infarction); 1/286 standard NRT group	AEs measured to 1 year. Treatment was for 8 or 24 weeks. AE denominators are participants followed. The myocardial infarction occurred before treatment started
Schnoll 2010b	Not reported	Not reported	4/321 patch group (including 2 strokes); 7/321 lozenge group (including 1 heart disease and 1 myocardial infarction)	AEs measured to 6 months. Treatment was for 12 weeks. AEs not reported in detail by relevant trial arms. All SAEs considered unrelated to study treatment (as did not occur whilst on treatment) except stroke in patch group.
Schnoll 2015	Not reported	Pounding heart: at 12 weeks: 0/128 (0%) 8‐week group; 1/137 (0.7%) 24‐week group; 2/121 (1.7%) 52‐week group. At 30 weeks: 2/103 (1.9%) 8‐week group; 1/116 (0.9%) 24‐week group; 1/103 (1.0%) 52 week group   Rapid heartbeat: 1/103 (1%) 8‐week group; 1/116 (0.9%) 24‐week group; 0/103 (0%) 52‐week group	4/180 8‐week patch group; 2/173 24‐week patch group; 8/172 52‐week patch group	Cardiac AEs are not cumulative across time points.
Schuurmans 2004	Not reported	Not reported	Not fully reported. One death in each group	AEs measured at all follow‐up visits (to 6 months). Treatment was for 12 weeks. AEs not reported in detail by relevant trial arms
Smith 2009	Not reported	Not reported	Not reported	No AE data reported
Smith 2013	Not reported	Not reported	0/490 2‐week NRT group; 0/497 6‐week NRT group; 0/494 patch group; 0/493 patch and gum group	No AE data reported
Stapleton 1995	8 (2%) overall. Not reported by trial arm	Not reported	Not reported	AEs measured at each visit. Not reported in detail by relevant trial arms
Preloading Investigators 2018	Not reported	Palpitations: 35/899 (3.9%) preloading group; 17/893 (1.9%) control group	8/899 preloading group (3 cardiac); 8/893 control group (0 cardiac)	AEs measured to 1 week post‐quit (1 week after preloading ceased)
TNSG 1991	11/262 (4.2%) 21 mg group; 15/275 (5.5%) 14 mg group; 1/127 (0.8%) 7 mg group	Not reported	0 SAEs in any group	AEs not reported in detail by relevant trial arms
Tønnesen 1988	0/27 (0%) 4 mg group; 1/33 (3%) 2 mg group	Palpitations: 1/27 (3.7%) 4 mg group; 0/33 (0%) 2 mg group	Not reported	AEs measured in counselling sessions during treatment (either 16 or 20 weeks)
Tønnesen 1996	0/45 (0%) ad libitum group; 0/44 (0%) fixed group	Palpitations: at 1 week: 1 moderate and 1 severe overall (not spilt by treatment group). At 6 weeks: 0% in both groups	0 SAEs in any group	AEs measured on treatment (up to 6 weeks)
Tønnesen 2000	Not reported	Not reported	0/109 5 mg patch group; 0/104 15 mg patch group; 0/118 inhaler group; 0/115 inhaler and 15 mg patch group	AEs measured at every follow‐up (to 12 months). Treatment could continue to 12 months
Tulloch 2016	5/245 (2%) patch and gum group; 4/245 (1.6%) patch group	Cardiovascular (e.g. palpitations, tachycardia, chest pain): 3/245 (1.2%) patch and fast‐acting NRT group; 5/245 (2%) patch only group	6/245 patch and gum group; 9/245 patch group	AEs measured at each appointment
Walker 2011	Not reported	Not reported	53/706 selection box group; 51/704 usual care group	SAEs measured to 6 months. Treatment was for 8 weeks.