Reviewing the Cardiovascular Safety Profile of Antimalarial Drugs

A systematic review, published this month in BMC Medicine, analyses the results of 177 trials conducted between 1982 and 2016, including 18,436 patients who underwent electrocardiographic (ECG) evaluation during malaria clinical trials.

The authors found that these serious cardiovascular side effects, which include sudden cardiac death, are very rare in the treatment of malaria with quinoline antimalarials. The work emphasises the importance of continued pharmacovigilance with the increasing use of quinoline antimalarials in mass treatment strategies such as intermittent preventative treatment (IPT) and mass drug administration (MDA).

Dr Haeusler, co-first author explains, "These findings are reassuring and build on existing evidence which suggests that cardiovascular adverse events are very rare following the use of quinoline antimalarials for the treatment of malaria. There were no cases of sudden unexplained death or life-threatening heart rhythm abnormalities in any of the 177 trials that were included in the review". Dr Chan, co-first author, adds, "At the same time, our findings also highlight the need for ongoing strengthening of pharmacovigilance systems to detect rare adverse events in the general population of malaria-endemic areas, not just within the confines of clinical trials."

The systematic review also highlights the extent of heterogeneous electrocardiographic measurement, analysis and reporting in malaria clinical trials. This, coupled with the large amount of missing outcome reporting in published trials, made a numerical comparison between trial results difficult. The research team therefore urgently call for a more standardised approach to the measurement and reporting of ECG data in malaria trials. To respond to this need, the WWARN Southern Africa Centre has just released a Guideline for the Collection of ECG data to support clinical trial managers with collecting standard 12-lead clinical trial ECG data.

Professor Philippe Guerin, Director of the WorldWide Antimalarial Resistance Network (WWARN) suggests, "With the potential to use the quinoline-containing dihydroartemisinin-piperaquine, an artemisinin-combination therapy, for large scale malaria control interventions, we need further individual patient data analyses to assess the effect of the quinoline antimalarials on the QT interval. We want to provide the best available trial tools and research evidence to support novel strategies that will help eliminate malaria and reduce the threat of widespread drug resistance."

Read the paper: Haeusler et al. The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review. BMC Medicine. 7 November 2018.