Abstract
Background and aims: Bruton tyrosine kinase inhibitors, such as ibrutinib, are medications that are actively used for Chronic Lymphocytic Leukemia (CLL) and several lymphomas. They work by inhibiting Bruton’s tyrosine kinase therefore affecting B cell proliferation. Ibrutinib itself is associated with multiple cardiotoxicities including atrial fibrillation, ventricular arrhythmias, heart failure, and bleeding. There are well-established studies that show the incidence of atrial fibrillation with ibrutinib therapy. However, only a few reports show an association between ibrutinib therapy and advanced heart block. Methods: A systematic review was carried out involving searching in research databases including PubMed using key search terms. This was followed by a meta-analysis that compared cholesterol, high density lipoprotein, low-density lipoprotein and triglycerides in a population taking combined oral contraceptive pills containing ethinyl oestradiol/levonorgestrel at 6 months vs the baseline measurement. Results: Six studies (9 intervention groups), totalling 274 participants were analysed. Hedge’s g for the cholesterol comparison was 0.133 (95% confidence intervals -0.058, 0.324; p=0.173; I2 =74.652), which was not significant. In contrast high density lipoprotein was significantly lower, Hedge’s g -0.546 (95% confidence intervals -0.834, -0.259; p<0.001; I2 =92.546) and lowdensity lipoprotein significantly higher, Hedge’s g 0.248 (95% confidence intervals 0.055, 0.442; p=0.012; I2 =83.116 as were the triglycerides, Hedge’s g 0.667 (95% confidence intervals 0.491, 0.842; p<0.001; I2 =64.627. Conclusion: After 6 months use the combined oral contraceptive pills containing ethinyl oestradiol/levonorgestrel led to a significantly increased concentration of low-density lipoprotein and triglycerides and a significantly lower concentration of high-density lipoprotein. More research is required to investigate whether these changes are associated with an increased risk of cardiovascular disease.
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