Aromatase inhibitors do not increase risk for serious cardiovascular events

Women with early-stage breast cancer treated exclusively with aromatase inhibitors did not face an increased risk for cardiac ischemia or stroke compared with women who received tamoxifen, according to retrospective study results.

However, aromatase inhibitors increased risk for less serious cardiovascular adverse events — including abnormal heartbeat and pericarditis — compared with tamoxifen, results showed.

Cardiovascular disease (CVD) is a frequent cause of death among elderly breast cancer survivors. Previous studies have demonstrated inconclusive evidence regarding whether aromatase inhibitors increase risk for CVD, and no other population-based studies have been able to adjust for CVD risk factors and medications.

Reina Haque , PhD, MPH, scientist in the department of research and evaluation at Kaiser Permanente Southern California, and colleagues sought to determine the long-term influence of adjuvant endocrine therapies on CVD risk in postmenopausal breast cancer survivors.

The study included data from 13,273 women (mean age, 66.8 ± 8.1 years) diagnosed with breast cancer between January 1991 and December 2010 and followed through December 2011, representing 72,886 person-years.

All women included in the study had hormone receptor-positive disease with no prior incidence of CVD.

The researchers used electronic health record information to capture information on demographics, comorbidity, medication, use and CVD risk. They categorized women based on receipt of endocrine therapy: tamoxifen only (31.7%; n = 4,207), aromatase inhibitors only (28.7%; n = 3,807), both tamoxifen and aromatase inhibitors (20.2%; n = 2,682), or no endocrine therapy (19.4%; n = 2,577).

Women who used tamoxifen only tended to be older, in the lower median quartile for household income and were less likely to be obese or overweight, whereas aromatase inhibitor users tended to have larger tumors diagnosed at a later stage than tamoxifen-only users, and received chemotherapy more frequently. Nearly all aromatase inhibitor users initiated therapy after the year 2000.

The person-year rates of CVD by therapy group served as the study’s primary outcome.

The researchers observed 3,711 cardiovascular events during a maximum follow-up of 21 years (median, 4.5 years).

Multivariable analyses adjusted for CVD medications, race/ethnicity, stage and age at diagnosis, and other factors showed that women who used aromatase inhibitors exclusively had similar risks for cardiac ischemia (adjusted HR = 0.97; 95% CI, 0.78-1.22) and stroke (adjusted HR = 0.97; 95% CI, 0.7-1.33) as tamoxifen-only users.

Heart failure and cardiomyopathy risk appeared slightly increased among women who used aromatase inhibitors alone (adjusted HR = 1.1; 95% CI, 0.86-1.4) or with tamoxifen (adjusted HR = 1.27; 95% CI, 0.99-1.6).

Additionally, women who used aromatase inhibitors exclusively had a 29% (HR = 1.29; 95% CI, 1.11-1.5) increased risk for other cardiovascular diseases — such as dysrhythmia, arrhythmia and pericarditis — compared with tamoxifen-only users. Women who used both endocrine therapies had a 26% (HR = 1.26; 95% CI, 1.09-1.45) increased risk for these conditions.

The researchers noted that BMI did not appear to be a significant confounding factor for CVD risk, and that the percentages of overweight or obese women were similar in all four groups.

A sensitivity analysis including women who underwent radiotherapy (n = 7,982) showed that women who used aromatase inhibitors exclusively and received left-sided breast radiotherapy had an increased risk for stroke (adjusted HR = 1.15; 95% CI, 0.69-1.92) and heart failure or cardiomyopathy (adjusted HR = 1.21; 95% CI, 0.79-1.83) compared with tamoxifen-only users.

The researchers acknowledged limitations, including their lack of access to data on smoking status, physical activity and over-the-counter drug use. They further noted that many records had missing BMI data, and that the electronic health records did not capture the types of chemotherapy used.

“Our study is a comprehensive assessment of the impact aromatase inhibitors have on cardiovascular risk and provides reassurance that the hormone therapy to reduce breast cancer recurrence does not increase risk for the most fatal cardiovascular events,” Haque said in a press release. “A particular strength of our study is that we accounted for women’s other potential cardiovascular risk factors, as well as medication to treat high blood pressure and high cholesterol.” – by Cameron Kelsall

Disclosure: The California Breast Cancer Research Program, the NIH and the NCI provided funding for this study. Haque reports institutional research funding from AstraZeneca and Novartis for matters not related to this study. Please see the full study for a list of all other researchers’ relevant financial disclosures.