Efficacy of cardioprotective agents in reduction of chemotherapy related cardiotoxicity

Background: We sought the efficacy of cardioprotective strategies in pts undergoing chemotherapy in a systemic review.

Methods: A systemic review using (PubMed, Embase, screening reference sections) was undertaken using the following keywords cardiomyopathy, early detection and treatment, prevention, statins/ beta blockers/ ACE inhibitors in PubMed. Studies were included if pts undergoing chemotherapy were administered prophylactic treatment. We excluded pts with heart failure, multiple organ failure or disseminated cancer.

Results: The initial search resulted in 1536 articles in the last 20 years. We excluded 1457 by topic review. We excluded 43 due to inability to match our inclusion criteria. After full text review, we selected 14 articles (n=3204, paediatric and adult) relating to anthracycline therapy. Amongst these, 3 were observational studies and the remainder, randomised controlled trials (RCT) (Table 1). The most common oncological condition was breast cancer. Dextrazoxane (DXO, RR 0.03-0.46), statins (RR 0.2), ACEi (RR 0.16-0.32) and beta blockade (RR 0.2) were effective in preventing LV dysfunction.

Table 1

Study name	Year	n	Age	Agent	Study type	Primary outcome	Effect size	p
Lipshultz	2004	206	7.5	DXO	RCT	HF	RR=0.41	p=0.22
Swain	1997	185	62	DXO	RCT	HF	RR=0.37	p=0.038
Lopez	1998	129	52	DXO	RCT	HF/EF	RR=0.32	p=0.004
Marty	2006	164	52	DXO	RCT	HF/EF	RR=0.12	p<0.05
Speyer	1992	150	55	DXO	RCT	HF	RR=0.10	p<0.0001
Swain	1997	349	58	DXO	RCT	HF/EF	RR=0.03	p<0.001
Venturini	1996	160	57	DXO	RCT	HF/EF	RR=0.46	p=0.006
Wexler	1996	38	14	DXO	RCT	CH/EF	RR=0.36	p<0.01
Seicean	2012	628	51	Statin	observational	HF	HR=0.30	p=0.03
Acar	2011	40	53	Statin	RCT	EF	RR=0.20	p<0.001
Silber	2010	135	7.7	ACEi	RCT	ExCI	RR=0.16	p=0.32
Blaes	2010	142	52	ACEi	Observational	EF	RR=0.32	P=0.094
Seicean	2013	920	52	BB	Observational	HF	HR=0.20	P=0.003
Kalay	2003	50	47.9	BB	RCT	EF	RR=0.20	p<0.001

Conclusions: Cardioprotection with DXO, ACE inhibitors, beta blockers and statins appear to have similar efficacy in prevention LV dysfunction.