Sodium-containing medications like paracetamol are associated with significantly increased risk of cardiovascular events and all-cause mortality, according to findings from a large new study published today in the European Heart Journal.

Data of nearly 300,000 individuals from the Health Improvement Network from 2000 to 2017 was analysed in this study. Health Improvement Network is a large UK database of electronic health records of almost 17 million people.

A total of 4532 hypertensives who had been prescribed sodium-containing paracetamol were compared with 146,866 patients with high blood pressure who had been prescribed paracetamol without sodium for a period of one year. The study also examined 147,299 individuals without a history of hypertension (5351 taking sodium-containing paracetamol and 141,948 taking non-sodium-containing paracetamol). The age of the participants ranged between 60 and 90 years. More women than men were taking sodium-containing acetaminophen.

Analysis revealed that hypertensive patients taking sodium-containing paracetamol were at a higher risk of heart attack, stroke or heart failure compared to those taking paracetamol without sodium; 5.6% (122 cases) vs 4.6% (3051 cases), respectively. Mortality was also increased at one year in these patients: 7.6% (404 deaths) vs 6.1% (5,510 deaths), respectively.

A similar trend was observed among non-hypertensive participants. The risk of CVD events in these participants was 4.4% (105 cases) versus 3.7% (2079 cases) among those taking non-sodium-containing paracetamol. The mortality in this group was also higher in those taking sodium-containing paracetamol; 7.3% (517 deaths) and 5.9% (5190 deaths), respectively.

Similar risks were observed for the subgroups of patients also using sodium-containing ibuprofen or ranitidine.

Sodium is frequently used to help drugs quickly dissolve and disintegrate in water. The effervescent and soluble formulations of 0.5 g tablets of paracetamol contain 0.44 and 0.39 g of sodium respectively. Therefore, intake of maximum daily dose (4 g/day) of sodium-containing paracetamol is equivalent to 3.5 and 3.1 g of sodium. Whereas, the World Health Organization (WHO) recommends approximately 2g sodium (less than 5 grams) per person per day.

This study has demonstrated increased risk of incident CVD and all-cause mortality with sodium-containing paracetamol among individuals with and without hypertension. The risk increased as the duration of intake increased.

Hypertensive patients are advised to reduce their salt intake. The sodium-containing effervescent tablets are a hidden source of sodium, which most people are unaware about. Since most of these medications are self-medications taken over the counter (OTC), it is important to educate the public at large about this risk. Hypertensive as well as non-hypertensive individuals should avoid intake of extra sodium through sodium-containing effervescent tablets. Clinicians too should be aware about sodium-containing paracetamol and the associated risks and avoid prescribing them to reduce the cardiovascular risk. This study also highlights the need for updating labels of all drugs including OTC drugs to include sodium content also in addition.

Reference         

1. Zheng C, et al. Sodium-containing acetaminophen and cardiovascular outcomes in individuals with and without hypertension. Eur Heart J.. 2022 Feb 24;ehac059. doi: 10.1093/eurheartj/ehac059.