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. 2019 May 7;3(7):1283–1301. doi: 10.1210/js.2019-00096

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.

a

CV events included AMI, angina, and cardiac failure. Refers to OR being used rather than RR.