Can ACE inhibitors/ARB antihypertensive drugs prevent cardiotoxicity caused by chemotherapy in early breast cancer?

Every October is World Breast Cancer Prevention and Control Month, which aims to convey the concept
of "early prevention, early detection and early treatment" to the whole society.
Breast cancer is one of the most common cancers in Chinese women, and its incidence cannot be
underestimated.
Although survival rates for breast cancer patients have improved significantly over the past decade, systemic chemotherapy is still considered the standard treatment for
breast cancer.
During chemotherapy, accompanied by the occurrence
of cardiotoxicity.

Anthracyclines are chemotherapy drugs
with dose-dependent activity.
The incidence of heart failure increases by 5% at a cumulative dose of 400 mg/m2 and rises to 16% at a dose of 500 mg/m2, at 700 mg/m2 The dose rises to 48%.

Trastuzumab is a humanized monoclonal antibody against HER-2 commonly used as adjuvant therapy
for early-stage breast cancer.
Trastuzumab has been reported to cause adverse cardiovascular events
.
Therefore, cardioprotective strategies are necessary to prevent or mitigate cardiotoxic events
in breast cancer patients.

Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) have been shown to inhibit chemotherapy-induced cardiomyopathy in early animal studies and in adult patients with cardiotoxicity.

However, the evidence is inconsistent
.
A meta-analysis published in the journal Transl Cancer Res evaluated the effect of ACE inhibitors/ARBs on cardiotoxicity induced by anthracycline chemotherapy with or without trastuzumab in patients with early-stage breast cancer
。

ACEI and ARB have a definite antihypertensive effect, especially in patients with heart failure, myocardial infarction, diabetes, and chronic kidney disease, and there is sufficient evidence to improve prognosis
.
The antihypertensive effect of ARB drugs is clear, the role of protecting target organs is certain, and there is no adverse effect on glycolipid metabolism; Indicated for grade 1 to 2 hypertension, especially in patients with hypertension complicated with left ventricular hypertrophy, heart failure, atrial fibrillation prevention, diabetic nephropathy, metabolic syndrome, microalbuminuria, and proteinuria
。

There are many types of ARB drugs, among which ACEI commonly used drugs are captopril, enalapril, lisinopril and ramipril, and ARB is often named "sartan", including valsartan, losartan, irbesartan, telmisartan, candesartan, olmesartan and alisartan
.

Among them, irbesartan has a large antihypertensive amplitude, a higher compliance rate of monotherapy to control blood pressure, high absorption, and a long duration of drug effect, which occupies an important position
in the treatment of hypertension.

The researchers systematically searched the Cochrane, PubMed, and Embase electronic databases, with keywords such as "breast cancer," "Cardiotoxicity", "Chemotherapy", "ACE inhibitors", and "ARBs.
" " for relevant randomized controlled trials (RCTs).

The primary endpoint of this meta-analysis was the change in mean left ventricular ejection fraction (LVEF) in the
ACEI/ARB group from baseline to study termination compared to the control group.
Secondary endpoints included baseline LVEF and incidence of
cardiac and hypotensive events due to anticancer therapy.

Results showed that 5 studies covering 702 patients with
early-stage breast cancer were included.
Compared with the control group, accepted There was a statistically significant difference in the mean LVEF change in patients treated with ACEI/ARB, with a mean difference of 4.
08% (95% CI: 0.
8% to 7.
35%，P=0.
01）
。 However, ACE/ARB did not significantly reduce the risk of cardiac events compared with control (OR 0.
91, 95% CI: 0.
62 to 1.
34).
P=0.
64) or increased incidence of hypotensive events (OR 2.
72, 95 % CI: 0.
69 to 10.
73, P=0.
15)
。 In addition, hypotensive events were reduced by a factor of 2.
72 in the ACEI/ARB group compared with the control group, but this difference was not statistically significant
.
Thus, ACE inhibitors/ARBs may be beneficial in
patients with early-stage breast cancer with cardiac insufficiency due to anthracycline chemotherapy and/or trastuzumab.

In summary, ACE inhibitors/ARBs are critical in reducing the amount of LVEF decline caused by anthracycline-based chemotherapy and/or trastuzumab, It makes it possible to become an indispensable treatment for breast cancer patients with cardiac insufficiency
.
In the future, further research is needed to determine whether it can significantly reduce the incidence of cardiotoxic events and improve survival after anti-cancer treatment in patients with early-stage breast cancer
.

Original provenance

Dong H, Yao L, Wang M, Wang M, Li X, Sun X, Yu X, Guo J, Li X, Xu Y.
Can ACEI/ARB prevent the cardiotoxicity caused by chemotherapy in early-stage breast cancer?-a meta-analysis of randomized controlled trials.
Transl Cancer Res.
2020 Nov; 9(11):7034-7043.
doi: 10.
21037/tcr-20-1869.
PMID: 35117309; PMCID: PMC8799108.