Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer? Meta-analysis of randomized trials.
BACKGROUND
Despite the advantages from using aromatase inhibitors (AIs) compared with tamoxifen for early breast cancer, an unexpectedly greater number of grade 3 and 4 cardiovascular events (CVAE) (as defined by National Cancer Institute of Canada-Common Toxicity Criteria [version 2.0] was demonstrated.


METHODS
Phase 3 randomized clinical trials (RCTs) comparing AI with tamoxifen in early breast cancer were considered eligible for this review. The event-based risk ratios (RRs) with 95% confidence intervals (95% CIs) were derived, and a test of heterogeneity was applied. Finally, absolute differences (ADs) in event rates and the number of patients needed to harm 1 patient (NNH) were determined.


RESULTS
Seven eligible RCTs (19,818 patients) reported CVAE results. When considering all RCTs, the AD of the primary endpoint (CVAE) between the 2 arms (0.52%), tamoxifen versus AI, was statistically significant (RR, 1.31; 95% CI, 1.07-1.60; P= .007). This translated into an NNH value of 189 patients; when only third-generation AIs were considered, the difference (0.57%) remained significant (RR, 1.34; 95% CI, 1.09-1.63; P= .0038). Thromboembolic events were significantly more frequent in the tamoxifen arm, regardless of the strategy adopted (RR, 0.53; 95% CI, 0.42-0.65; P< .0001), without significant heterogeneity (P= .21). An AD of 1.17% and an NNH value of 85 patients were observed.


CONCLUSIONS
According to the results from this meta-analysis, the risk of grade 3 and 4 CVAEs in patients who were receiving AIs was higher compared with the risk in patients who were receiving tamoxifen, and the difference reached statistical significance. However, the AD was relatively low, and from 160 to 180 patients had to be treated to produce 1 event.
Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy.
Federica
F
Cuppone
Emilio
E
Bria
Sunil
S
Verma
Kathleen I
KI
Pritchard
Sonal
S
Gandhi
Paolo
P
Carlini
Michele
M
Milella
Cecilia
C
Nisticò
Edmondo
E
Terzoli
Francesco
F
Cognetti
Diana
D
Giannarelli
D047072:Aromatase Inhibitors / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000009:adverse effects
D047072:Aromatase Inhibitors; D013629:Tamoxifen