Letrozole and Risk of Blood Clots
Letrozole does not increase the risk of blood clots or thromboembolic events compared to tamoxifen. In fact, tamoxifen is associated with a significantly higher incidence of thromboembolic events compared to letrozole. 1
Evidence from Clinical Trials
The BIG 1-98 trial, which compared letrozole to tamoxifen in postmenopausal women with hormone receptor-positive breast cancer, demonstrated that both the overall incidence and incidence of grade 3 to 5 thromboembolic events were significantly higher in the tamoxifen arm compared to the letrozole arm. 1
According to the FDA label for letrozole, thromboembolic events occurred at a lower rate in patients receiving letrozole (3.2%) compared to those receiving tamoxifen (4.6%) at a median follow-up of 96 months. 2
When considering treatment duration of 60 months, thromboembolic events were observed in 2.1% of patients on letrozole versus 3.6% of patients on tamoxifen. 2
Cardiovascular Effects of Letrozole
While letrozole does not increase thromboembolic risk, it is associated with a higher incidence of grade 3 to 5 cardiac adverse events compared to tamoxifen. 1
The overall incidence of cardiac adverse events was similar between letrozole (4.8%) and tamoxifen (4.7%) in the BIG 1-98 trial. 1
Myocardial infarction was reported more frequently with letrozole (1.0%) compared to tamoxifen (0.5%) during study treatment. 2
Other Safety Considerations with Letrozole
Letrozole is associated with a higher incidence of bone fractures (10.1% vs 7.1%) compared to tamoxifen. 2
Letrozole may cause hypercholesterolemia, with 52.3% of patients experiencing this side effect in clinical trials. 2
Common side effects of letrozole include arthralgia/arthritis (25.4%), hot flashes (33.5%), and night sweats (14.5%). 2
Clinical Implications
For patients with a history of thromboembolic events or at high risk for thrombosis, letrozole may be a safer choice than tamoxifen. 1, 2
In real-world settings, breast cancer patients treated with ribociclib (a CDK4/6 inhibitor) combined with letrozole or fulvestrant did not show higher risk for thromboembolic events, further supporting the safety profile of letrozole regarding thrombosis risk. 3
Patients should be monitored for other cardiovascular effects, particularly cardiac events, when taking letrozole. 1
Summary
Letrozole is not associated with an increased risk of blood clots compared to tamoxifen. In fact, the evidence from large clinical trials shows that tamoxifen carries a significantly higher risk of thromboembolic events. When considering antiestrogen therapy for breast cancer patients with a history of or risk factors for thrombosis, letrozole represents a safer alternative to tamoxifen with respect to thromboembolic risk.