PB1795 CARDIOPROTECTIVE EFFECTS OF ATORVASTATIN IN B‐CELL LYMPHOMA PATIENTS RECEIVING RCHOP REGIMEN, A RANDOMIZED CONTROLLED TRIAL
Authors: Koonarat A. , Norasetthada L. , Chai‐Adisaksopha C. , Tantiworawit A. , Rattarittamrong E. , Rattanathammethee T. , Yongsmith L. , Wongcharoen W. , Phrommintikul A. , Apaijai N. , Chattipakorn S. , Chattipakorn N. 
Published: June 2019

Background:

Cardiac toxicity is one of the major complications from anthracycline. Pre‐clinical studies revealed that statin may reduce cardiotoxicity from anthracycline‐based chemotherapy.

Aims:

We therefore conducted an open‐labeled randomized controlled trial investigating the efficacy of atorvastatin in the prevention of anthracycline‐associated cardiotoxicity.

Methods:

We enrolled patients who were newly diagnosed with aggressive B‐lymphoma, age 18‐70 years, and planned to receive RCHOP. Patients were excluded if they 1) had abnormal cardiac function at baseline, 2) currently received beta‐blockers, ACE inhibitors or statins, and 3) expecting mediastinal radiotherapy. Patients were randomized into either atorvastatin or control group, stratified by the international prognostic index (IPI), cardiovascular risks and pre‐specified numbers of cycle of chemotherapy. Atorvastatin 40 mg/day was given from the first cycle until completion of chemotherapy. Primary outcomes were changes of high‐sensitivity troponin‐I (hsTrop‐I) and pro B‐type natriuretic peptide (pro‐BNP) levels. Major secondary outcomes were changes in echocardiographic parameters, inflammatory markers, mitochondrial oxidative stress and rate of apoptosis.

Results:

Of 50 enrolled patients, 26 were randomized into atorvastatin group and 24 into control group. The baseline characteristics were balance between two groups. However, patients in atorvastatin group were older than those in control group (median age of 60 vs 56 years, P = 0.005). The increment of serum hsTrop‐I level was lower among patients receiving atorvastatin as compared to controls with a mean difference of 33.92 ± 29.21 vs 53.33 ± 55.81 ng/l (P = 0.26) (Figure 1). Proportion of late apoptosis of peripheral blood mononuclear cells, measuring on cycle 4‐6 of chemotherapy was significantly lower in atorvastatin arm (P = 0.01). There was no significant difference in the changes of serum pro‐BNP, erythrocyte sedimentation rate, C‐reactive protein levels and mitochondrial oxidative stress. At the end of treatment, the changes of left ventricular ejection fraction (LVEF) (4.65% vs 4.26%, P = 0.09) and global longitudinal strain changes (GLS) (1.86 vs 1.47, P = 0.07) were not statistically significant among two groups. There was no difference of grade 3‐4 hematologic adverse events (AEs). Although, one patient in atorvastatin arm had grade 3‐4 non‐hematologic adverse event, which was not related to study drug.

Summary/Conclusion:

Atorvastatin showed a potential effect on a cardio‐protection in patient receiving RCHOP regimen, by reducing the increment of serum hsTrop‐I and proportion of apoptosis. Although, there was no significant difference of echocardiographic parameter at the end of treatment, the longer follow‐up of LVEF and GLS would help to confirm the potential benefit of atorvastatin.

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