Excess Sodium in Soluble Acetaminophen Tied to CVD Risk, Death

Megan Brooks

February 24, 2022

Regular use of acetaminophen, also known as paracetamol, in effervescent or soluble formulations that contain sodium increases the risk of cardiovascular disease (CVD) and death in people with or without hypertension, a large observational study of more than 300,000 adults suggests.

"Numerous studies have reported that high sodium intake is associated with increased risks of cardiovascular disease," Yuqing Zhang, with Massachusetts General Hospital and Harvard Medical School, Boston, told theheart.org | Medscape Cardiology.

"Given that the pain relief effect of non-sodium-containing acetaminophen is similar to that of sodium-containing acetaminophen, clinicians may prescribe non-sodium-containing acetaminophen to their patients to minimize the risk of CVD and mortality," Zhang said.

The study was published online February 24 in the European Heart Journal.

"Compelling Results"

Zhang and colleagues note that the effervescent and soluble formulations of 0.5 g acetaminophen contain 0.44 and 0.39 g of sodium, respectively.

Therefore, the intake of maximum daily dose (ie, 4 g/day) of sodium-containing acetaminophen corresponds to the ingestion of more than 3 g of sodium ― a dose that alone exceeds the recommended total daily sodium intake allowance of the World Health Organization (ie, 2 g/day).

"This hidden extra-sodium intake is often overlooked," Zhang told theheart.org | Medscape Cardiology.

Using data from the Health Improvement Network, a UK primary care database, the researchers examined 4532 patients with hypertension taking sodium-containing acetaminophen and compared them with 146,866 patients with hypertension taking non-sodium-containing acetaminophen (tablet, capsule, or oral suspension formulations).

After 1 year, the risk of incident CVD (myocardial infarction, stroke, and heart failure) was 5.6% in those taking sodium-containing acetaminophen, compared was 4.6% in those taking non-sodium-containing acetaminophen (average weighted hazard ratio [HR] = 1.59; 95% CI, 1.32 – 1.92).

A separate analysis of normotensive patients taking sodium-containing acetaminophen (n = 5351) or non-sodium-containing acetaminophen (n = 141,948) gave similar results.

The 1-year risk of incident CVD was 4.4% in those taking sodium-containing acetaminophen vs 3.7% among those taking non-sodium-containing acetaminophen (average weighted HR = 1.45; 95% CI, 1.18 – 1.79).

There was also evidence of a dose-response relationship.

In those with hypertension, CVD risk increased by roughly one quarter (odds ratio [OR], 1.26) for those with one prescription of sodium-containing acetaminophen and by nearly one half (OR, 1.45) for those with five or more prescriptions of sodium-containing acetaminophen. Similar findings were observed among adults without hypertension.

Mortality at 1 year was also higher in those taking sodium-containing acetaminophen than non-sodium-containing acetaminophen, in patients with hypertension (7.6% vs 6.1%) and without hypertension (7.3% vs 5.9%).

"The results are compelling," write the authors of an editorial published with the study.

"The direct message from this study is clear ― there are likely to be millions of people worldwide taking paracetamol on a daily basis in a 'fast-acting' effervescent or soluble formulation who are increasing their risks of cardiovascular disease and premature death," say Aletta Schutte, PhD, and Bruce Neal, MBChB, PhD, the George Institute for Global Health, Sydney, Australia.

"The weight of the evidence makes ongoing inaction on sodium-containing medications untenable. The widespread use of effervescent medication in the general population, and the enormous doses of sodium that can be consumed inadvertently by unsuspecting consumers requires urgent action," Schutte and Neal say.

The study was supported by the National Natural Science Foundation of China, the National Key Research and Development Project, the Project Program of National Clinical Research Center for Geriatric Disorders, the Key Research and Development Program of Hunan Province, and the Science and Technology Program of Hunan Province. Zhang, Schutte, and Neal have disclosed no relevant financial relationships.

Eur Heart J. Published online February 24, 2022. Full text, Editorial

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