. 2011 Sep 6;183(12):1359–1366. doi: 10.1503/cmaj.110218

Table 1:

Characteristics of randomized controlled trials of varenicline included in the analysis of serious adverse cardiovascular events^*

Study	Duration of treatment, wk	Duration of study, wk	Primary outcome	Cardiac exclusions at enrolment	Drug and dose	No. of participants	Age, yr, mean (SD or range)	Males, %
Protocol A3051080, 2010¹⁶	12	26	Continous abstinence rate	Clinically significant CVD in last 6 mo, systolic BP > 150 mm Hg	Varenicline 1 mg bid	394	43.1 (18–69)	60.4
Protocol A3051080, 2010¹⁶	12	26	Continous abstinence rate		Placebo	199	43.9 (20–71)	60.4^‡
Protocol A3051095, 2010¹⁷	12	24	Continous quit rate, continous abstinence rate	No serious or unstable disease in last 6 mo	Varenicline 1 mg bid	493	43.9 (18–75)	60.3
Protocol A3051095, 2010¹⁷	12	24	Continous quit rate, continous abstinence rate	No serious or unstable disease in last 6 mo	Placebo	166	43.2 (18–72)	60.0
Fagerstrom et al., 2010¹⁸	12	26	Continous quit rate	Any serious medical condition	Varenicline 1 mg bid	214	43.9 (12.0)	88.7
Fagerstrom et al., 2010¹⁸	12	26	Continous quit rate	Any serious medical condition	Placebo	218	43.9 (12.0)	89.9
Gonzales et al., 2006¹⁹	12	52	Continous quit rate	CVD within last 6 mo	Varenicline 1 mg bid	352	42.5 (11.1)	50.0
					Bupropion 150 mg bid	329	42.0 (11.7)	58.4
					Placebo	344	42.6 (11.8)	54.1
Jorenby et al., 2006²⁰	12	52	Continous quit rate	Clinically significant CVD in last 6 mo	Varenicline 1 mg bid	344	44.6 (11.4)	55.2
					Bupropion 150 mg bid	342	42.9 (11.9)	60.2
					Placebo	341	42.3 (11.6)	58.1
Nakamura et al., 2007²¹	12	52	Continous abstinence rate	Unstable CVD	Varenicline 1 mg bid	156	40.1 (11.6)	79.2
					Varenicline 0.5 mg bid	156	39.0 (12.0)	71.1
					Varenicline 0.25 mg bid	153	40.2 (12.3)	72.7
					Placebo	154	39.9 (12.3)	76
Niaura et al., 2008²²	12	52	Continous abstinence rate	History of CVD	Varenicline 1 mg/d	160	41.5 (11.3)	50.3
Niaura et al., 2008²²	12	52	Continous abstinence rate	History of CVD	Placebo	160	42.1 (11.7)	53.5
Nides et al., 2006²³	7	52	Continous abstinence rate	History of CVD	Varenicline 0.3 mg/d	128	41.9 (10.6)	50.0
					Varenicline 1 mg/d	128	42.9 (10.5)	43.7
					Varenicline 1 mg bid	127	41.9 (9.8)	50.4
					Bupropion 150 mg bid	128	40.5 (10.8)	45.2
					Placebo	127	41.6 (10.4)	52.0
Oncken et al., 2006²⁴	12	52	Continous abstinence rate	History of CVD	Varenicline 1 mg bid titrated	130	42.2 (10.7)	48.5
					Varenicline 1 mg bid nontitrated	129	43.7 (10.0)	48.8
					Varenicline 0.5 mg bid titrated	130	43.5 (10.5)	53.1
					Varenicline 0.5 mg bid nontitrated	129	42.9 (10.1)	45.0
					Placebo	129	43.0 (9.4)	51.9
Rigotti et al., 2010⁹	12	52	Continous abstinence rate	Excluded if unstable CVD in last 2 mo; included with stable CVD^§	Varenicline 1 mg bid	355	57.0 (8.6)	75.2
Rigotti et al., 2010⁹	12	52	Continous abstinence rate		Placebo	359	55.9 (8.3)	82.2
Tashkin et al.,^† 2010²⁵	12	52	Continous abstinence rate	Unstable CVD or history of CVD in last 6 mo	Varenicline 1 mg bid	250	57.2 (35–83)	62.5
Tashkin et al.,^† 2010²⁵	12	52	Continous abstinence rate	Unstable CVD or history of CVD in last 6 mo	Placebo	254	57.1 (34–77)	62.2
Tonstad et al., 2006²⁶	12	52	Long-term quit rate	CVD within last 6 mo	Varenicline 1 mg bid	603	45.4 (10.4)	50.2
Tonstad et al., 2006²⁶	12	52	Long-term quit rate	CVD within last 6 mo	Placebo	607	45.3 (10.4)	48.3
Tsai et al., 2007²⁷	12	24	Continous abstinence rate	Unstable CVD	Varenicline 1 mg bid	126	39.7 (9.3)	84.9
Tsai et al., 2007²⁷	12	24	Continous abstinence rate	Unstable CVD	Placebo	124	40.9 (11.1)	92.7
Williams et al., 2007²⁸	52	52	Long-term safety	Clinically significant CVD in last 6 mo	Varenicline 1 mg bid	251	48.2 (12.3)	50.6
Williams et al., 2007²⁸	52	52	Long-term safety	Clinically significant CVD in last 6 mo	Placebo	126	46.6 (12.1)	48.4
Aubin et al., 2008²⁹	12	52	Continous abstinence rate	Serious or unstable disease in last 6 mo	Varenicline 1 mg bid	378	42.9 (10.5)	48.4
Aubin et al., 2008²⁹	12	52	Continous abstinence rate	Serious or unstable disease in last 6 mo	Nicotine transdermal patch	379	42.9 (12.0)	50.0

Note: BP = blood pressure, CVD = cardiovascular disease, SD = standard deviation.

All but one of the trials involved smokers; the study by Fagerstrom et al.¹⁸ involved users of smokeless tobacco. Additional study characteristics are available in Appendix 2 (www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.110218/-/DC1).

^†

Investigators enrolled smokers with mild to moderate chronic obstructive pulmonary disease.

^‡

The proportion of males in study overall; the proportion in each study arm was not reported.

^§

The proportion of participants with cardiac disease in varenicline versus placebo groups was angina 53.2% v. 47.9%, myocardial infarction 45.9% v. 52.4%, prior coronary revascularization 46.2% v. 51.5%, and stroke 4.5% v. 6.7%.