. 2022 Sep 29;15:3049–3067. doi: 10.2147/DMSO.S381652

Table 5.

Studies Reporting on Myocardial Infarction

	Author	Year	Study Design	Study Indication	Reported Length of Follow-Up	No. Patients	Outcome	Adverse Event Frequency, Treatment Group	Adverse Event Frequency, Comparator Group	Effect Measure
Contrave^®	Apovian⁵³	2013	RCT	Weight loss	56 weeks; 28 weeks for primary efficacy analyses	1,484	Myocardial infarction	Naltrexone-bupropion: 1/992 (0.1%) Naltrexone-bupropion treated participant had active coronary artery disease, angina pectoris, hyperlipidemia, and hypertension.	Placebo: 0/492 (0.0%)	Fisher’s exact p = 1.00 (calculated)
	Nissen⁷⁸	2016	RCT	Weight loss	Median 121 weeks, interquartile range 114–128 weeks	8,905	Nonfatal myocardial infarction	Naltrexone-bupropion:	Placebo:	HR (99.7% CI)
								68/4455 (1.5%) at end of study	67/4450 (1.5%) at end of study	1.01 (0.61–1.66) at end of study
								54/4455 (1.2%) at 50% interim	54/4450 (1.2%) at 50% interim	1.00 (0.57–1.75) at 50% interim
								23/4455 (0.5%) at 25% interim	33/4450 (0.7%) at 25% interim	0.70 (0.41–1.18) at 25% interim
							Fatal or nonfatal myocardial infarction	Naltrexone-bupropion:	Placebo:	HR (99.7% CI)
								69/4455 (1.5%) at end of study	71/4450 (1.6%) at end of study	0.96 (0.59–1.58) at end of study
								55/4455 (1.2%) at 50% interim	57/4450 (1.3%) at 50% interim	0.96 (0.55–1.67) at 50% interim
								24/4455 (0.5%) at 25% interim	34/4450 (0.8%) at 25% interim	0.70 (0.42–1.19) at 25% interim
							Nonfatal myocardial infarction within 30 days of last treatment	Naltrexone-bupropion:	Placebo:	HR (99.7% CI)
								26/4455 (0.6%) at end of study	22/4450 (0.5%) at end of study	0.98 (0.42–2.30) at end of study
								24/4455 (0.5%) at 50% interim	21/4450 (0.5%) at 50% interim	0.96 (0.40–2.3) at 50% interim
								13/4455 (0.3%) at 25% interim	16/4450 (0.4%) at 25% interim	0.77 (0.37–1.60) at 25% interim
Bupropion	Benowitz⁵⁴	2018	RCT	Smoking cessation	52 weeks	8,058	Nonfatal MI	Bupropion: 4/2006 (0.2%)	Varenicline: 2/2016 (0.1%)	Varenicline: Fisher’s exact p = 0.45 (calculated) NRT: Fisher’s exact p = 0.73 (calculated) Placebo: Fisher’s exact p = 1.00 (calculated)
									NRT: 3/2022 (0.1%)
									Placebo: 5/2014 (0.2%)
	Chen⁵⁸	2021	Observational cohort	Psychiatric	Maximum 1999–2013	500,990	Myocardial infarction	NR	NR	HR (95% CI) Bupropion ≥ 180 days vs 0 or < 180 days: adjusted 1.25 (0.78–2.03) Bupropion < 180 cumulative defined daily doses vs 0: adjusted 1.024 (0.664–1.580) Bupropion ≥ 180 cumulative defined daily doses vs 0: adjusted: 0.528 (0.075–3.733)
	Eisenberg⁶²	2013	RCT	Smoking cessation	12 months; 9 weeks for primary analysis	392	Myocardial infarction	Bupropion: 5/192 (2.6%)	Placebo: 5/200 (2.5%)	Fisher’s exact p = 1.00 (calculated)
	Graham⁶⁴	2014	Observational cohort	Smoking cessation	6 months	88,957	Acute myocardial infarction	Bupropion: 31/14,133 (0.2%)	Varenicline: 133/74,824 (0.2%)	Adjusted HR (95% CI) 0.79 (0.5–1.24)
	Kittle⁶⁹	2017	RCT	Smoking cessation	≥ 6 weeks	7,224	Nonfatal myocardial infarction	Bupropion vs placebo: 2/4297 (Proportion: 0.047%; 95% CI, 0.006–0.168%)	Placebo comparator: 3/2927 (Proportion: 0.102%; 95% CI, 0.021–0.299%)	Fisher’s exact p = 0.40 (calculated)
	Monárrez-Espino⁷⁷	2018	Other observational	Smoking cessation	12 weeks	325,708	Myocardial infarction	Bupropion: 1–14 days before event: 16 discordant pairs during case period, 14 during control period 15–28 days before event: 14 discordant pairs during case period, 19 during control period 29–84 days before event: 47 discordant pairs during case period, 60 during control period 1–84 days before event: 73 discordant pairs during case period, 86 during control period	Varenicline: 1–14 days before event: 46 discordant pairs during case period, 43 during control period 15–28 days before event: 40 discordant pairs during case period, 43 during control period 29–84 days before event: 107 discordant pairs during case period, 140 during control period 1–84 days before event: 171 discordant pairs during case period, 173 during control period	OR (95% CI) Bupropion vs none: 1–14 days before event: 1.14 (0.55–2.34) 15–28 days before event: 0.73 (0.36–1.46) 29–84 days before event: 0.78 (0.53–1.14) 1–84 days before event: 0.84 (0.62–1.15)
Naltrexone	Garbutt⁶³	2016	RCT	Substance use	12 weeks	80	Myocardial infarction	Naltrexone: 1/40 (2.5%) ”One serious adverse event, a myocardial infarction, was not attributed to naltrexone treatment”	Placebo: 0/40 (0.0%)	Fisher’s exact p = 1.00 (calculated)