Table 2.
Meta-Analyses Reporting Cardiovascular Risk Associated With Adjuvant Endocrine Therapies
Study | Inclusion Criteria | Study Population | Comparison | Results, RR or ORa [95% CI] | Comments |
---|---|---|---|---|---|
Braithwaite et al., 2003 [93] | Breast cancer RCTs comparing TAM to placebo/no treatment | 32 RCTs; 52,529 women; average age 55 y | TAM vs placebo/no treatment | Stroke 1.49 [1.16–1.90] | |
AMI 0.62 [0.41–0.93] | |||||
AMI incidence 0.90 [0.66–1.23] | |||||
PE 1.88 [1.17–3.01] | |||||
DVT 1.87 [1.33–2.64] | |||||
Cuppone et al., 2007 [94] | Phase III RCTs comparing AIs (either upfront or sequential after 2 to 3 y of TAM) with TAM | 7 RCTs; 19,818 postmenopausal women | AI vs TAM | CV events 1.31 [1.07–1.60] | AD 0.5% (NNH = 189) |
Thromboembolic events 0.53 [0.42–0.65] | AD −1.2% (NNH = −85) | ||||
Cerebrovascular events 0.76 [0.58–1.003] | RR combine upfront and sequential treatment | ||||
Amir et al., 2011 [95] | Phase III RCTs >5 y in duration comparing AIs with TAM as primary endocrine therapy | 7 RCTs; 30,032 postmenopausal women | AI vs TAM | CV events 1.26a [1.10–1.43] | AD 0.8% (NNH = 132) |
Venous thrombosis 0.55a [0.46–0.64] | AD −1.3% (NNH = −79) | ||||
Cerebrovascular events 1.01 [0.81–1.26] | |||||
Aydiner 2013 [96] | RCTs comparing AIs with TAM as primary, sequential, or extended therapy (after 5 y of initial adjuvant endocrine therapy) | 11 RCTs; 34,070 postmenopausal women | AI vs TAM | Total CV events 1.20a [1.02–1.42] | ORs refer to primary AI therapy; ORs for CV events were similar for sequenced therapy, but not significant for extended therapy |
Thromboembolic events 0.61a [0.50–0.75] | |||||
Ryden 2016 [97] | RCTs comparing AIs with TAM as primary, sequential; or extended therapy with at least 5-year follow-up | 8 RCTs; 34,489 postmenopausal women | AI vs TAM | Total CV events 1.13 [0.96–1.33] | RR refers to primary AI therapy; RRs for sequenced and extended therapy were also not significant |
Khosrow-Khavar et al., 2016 [98] | Phase III RCTs comparing AIs with TAM, AIs to placebo/no treatment; and TAM to placebo/no treatment | 19 RCTs; 62,345 women | AI vs TAM TAM vs placebo/no treatment | Total CV events | Similar CV event results reported with sequential AI treatment; no difference in cerebrovascular events between treatments |
Primary AI vs TAM 1.19 [1.07–1.34] | |||||
TAM vs placebo/no treatment 0.67 [0.45–0.98] | |||||
Goldvaser et al., 2017 [99] | Phase III RCTs comparing extended AIs with placebo/no treatment | 7 RCTs; 16,3499 postmenopausal women | AI vs placebo/no treatment | Total CV events 1.18a [1.00–1.40] | AD 0.8% (NNH =1 22) |
No association between AIs and hypertension | |||||
Matthews et al., 2018 [100] | Studies investigating risk of CV outcomes with use of either TAM or AI or comparing the two treatments | 15 RCTs; 11 observational studies | AI vs TAM TAM vs placebo/no treatment | Thromboembolic events | No meta-analyses conducted for other outcomes |
Primary AI vs TAM 0.61 [0.58–0.63] | |||||
Heart failure | |||||
Tamoxifen vs placebo/no treatment 0.84 [0.56–1.07] |
Adapted and updated from Matthews et al. [100].
Cerebrovascular events included stroke and transient ischemic attack.
Abbreviations: AD, absolute difference; AI, aromatase inhibitor; AMI, acute myocardial infarction; CV, cardiovascular; DVT, deep venous thrombosis; NNH, number needed to harm; PE, pulmonary embolism; RR, relative risk; TAM, tamoxifen.
CV events included AMI, angina, and cardiac failure. Refers to OR being used rather than RR.