From the Guidelines
Letrozole can cause cardiac side effects, though they are generally uncommon, with a similar overall incidence of cardiac adverse events compared to tamoxifen, but a higher incidence of grade 3 to 5 cardiac adverse events. The most significant cardiac concerns include increased risk of ischemic cardiovascular events, particularly in patients with pre-existing heart disease. Patients may experience chest pain, palpitations, tachycardia, and rarely, heart failure. Letrozole can also cause hypercholesterolemia in some patients, which may indirectly impact cardiovascular health over time. These side effects occur because letrozole, as an aromatase inhibitor, reduces estrogen levels, which can affect lipid profiles and vascular function.
- Key points to consider:
- The BIG 1-98 trial showed a similar overall incidence of cardiac adverse events between letrozole and tamoxifen, but a higher incidence of grade 3 to 5 cardiac adverse events with letrozole 1.
- Patients with pre-existing cardiovascular disease should be monitored more closely while on letrozole therapy.
- Regular cardiac assessments, including blood pressure monitoring and lipid profile testing, are recommended during treatment.
- If a patient develops new or worsening cardiac symptoms while taking letrozole, they should seek medical attention promptly.
- Alternative hormonal therapies might be considered for patients at high cardiovascular risk, though this requires careful discussion of the risk-benefit profile with their healthcare provider.
- The evidence from the BIG 1-98 trial 1 and other studies suggests that letrozole is generally safe in terms of cardiac side effects, but patients should be closely monitored and alternative therapies considered if necessary.
From the FDA Drug Label
Adverse reactions that were reported in at least 5% of the patients treated with letrozole 0. 5 mg, letrozole 2. 5 mg, megestrol acetate, or aminoglutethimide in the two controlled trials AR/BC2 and AR/BC3 are shown in Table 5 ... Cardiovascular Hypertension 5 7 5 6
First and Second-Line Treatment of Advanced Breast Cancer In the combined analysis of the first- and second-line metastatic trials and post-marketing experiences other adverse reactions that were reported were ... cardiac failure, palpitations, tachycardia, arterial thrombosis
Cardiac side effects of letrozole include:
- Hypertension (reported in 5-7% of patients)
- Cardiac failure (reported in post-marketing experiences)
- Palpitations (reported in post-marketing experiences)
- Tachycardia (reported in post-marketing experiences)
- Arterial thrombosis (reported in post-marketing experiences)
From the Research
Letrozole and Cardiac Side Effects
- Letrozole, an aromatase inhibitor, has been reported to cause cardiac side effects, including acute heart failure 3.
- A case study found that a patient who developed acute heart failure after starting letrozole treatment showed improvement in cardiac function after the treatment was stopped, suggesting that letrozole-induced heart failure may be reversible 3.
- Another study found that letrozole accelerates metabolic remodeling in cardiomyocytes, leading to a shift from β-oxidation to glycolysis, which can lower energy supply to the heart and predispose to heart failure 4.
Cardiovascular Safety Profiles of Aromatase Inhibitors
- A comparative review of aromatase inhibitors found that letrozole may be associated with a significantly greater incidence of cardiovascular events and a numerical increase in cerebrovascular and cardiac deaths compared to tamoxifen 5.
- However, another study found that letrozole does not significantly alter serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, or lipoprotein(a) in non-hyperlipidemic postmenopausal women with primary breast cancer treated up to 36 months following at least 5 years of adjuvant tamoxifen therapy 6.
Effects of Letrozole on Lipid Profile
- Letrozole has been found to have an unfavorable effect on the serum lipid profile, with significant increases in total cholesterol, LDL cholesterol, and apolipoprotein B levels, as well as in the atherogenic risk ratios total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol 7.
- However, another study found that letrozole does not significantly alter serum lipid parameters in non-hyperlipidemic postmenopausal women with primary breast cancer 6.