Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: a systematic review and meta-analysis

Publication date: Available online 30 December 2016
Source:Cancer Treatment Reviews
Author(s): Husam Abdel-Qadir, Josee-Lyne Ethier, Douglas S. Lee, Paaladinesh Thavendiranathan, Eitan Amir
BackgroundThe cardiovascular risk of angiogenesis inhibitors is not well-quantified. We hypothesized that, compared to direct vascular endothelial growth factor (VEGF) inhibitors (anti-VEGF antibodies or decoy receptors), small molecule agents have higher risk due to their less specific mechanism.MethodsWe searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for phase III randomised controlled trials comparing angiogenesis inhibitor-based therapy to other systemic therapy. Outcomes evaluated were hypertension, severe hypertension, cardiac dysfunction, congestive heart failure, cardiac ischemia, arterial thromboembolism, venous thromboembolism, and fatal cardiovascular events. Data were pooled using Mantel-Haenszel random effects method to generate odds ratios (OR).ResultsWe identified 77 studies meeting inclusion criteria. Compared to routine care, angiogenesis inhibitors were associated with a higher risk of hypertension (OR 5.28 [4.53–6.15], number needed to harm [NNH] 6), severe hypertension (OR 5.59 [4.67–6.69], NNH 22), cardiac ischemia (OR 2.83 [1.72–4.65], NNH 84) and cardiac dysfunction (OR 1.35 [1.06–1.70], NNH 139). VEGF inhibitors were associated with an increased risk of arterial thromboembolism (OR 1.52 [1.17,1.98], NNH 140). No significant interaction was observed between the two drug subgroups for any outcomes. We identified no significant increase in the risk of the other outcomes evaluated.ConclusionAngiogenesis inhibitors increase the risk of hypertension, arterial thromboembolism, cardiac ischemia and cardiac dysfunction. There was no significant difference in cardiovascular risk between direct VEGF inhibitors and small molecule agents.



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