Cardiovascular risk associated with high sodium-containing drugs: A systematic review

Abstract

BackgroundExcess dietary sodium is associated with increased blood pressure (BP). Some drugs are associated with high sodium intake (in particular effervescent tablets), but the cardiovascular risk associated with such high sodium-containing drugs (HSCD) is largely underevaluated.ObjectivesTo summarize the evidence for a potential cardiovascular risk associated with exposure to HSCD, and to highlight possible risk factors associated with this iatrogenic issue; in general and/or specific populations.MethodsWe conducted a systematic review, by searching electronic databases including MEDLINE, EMBASE, Web of Science, CENTRAL and grey literature between 1960 and 2015. We included studies that reported modification of cardiovascular parameters or incidence/prevalence of cardiovascular outcomes, between a group of subjects exposed to HSCD relative to a non-exposed group. The threshold used to identify HSCD was 391 mg/day. We did not consider studies evaluating exposure to sodium as an active ingredient or those focusing on dialysis solutions or enteral/parenteral nutrition. Study quality was assessed using the EPHPP tool.ResultsA total of eight studies met our inclusion criteria. Four reported results for short-term exposure to HSCD (≤ 7 days) on BP fluctuations. One study reported an elevation of BP (associated sodium intake: 1,656 mg/day). Four studies evaluated a long-term exposure (≥ 2 years or discontinuation of a chronic treatment). Two studies reported iatrogenic risk. For these studies, drug associated sodium intake was high (> 1,500 mg/day) in patients with comorbidities (in particular, diabetes mellitus and hypertension).ConclusionDespite numerous study limitations, this systematic review suggests three potential synergistic risk factors for cardiovascular complications after exposure to HSCD: a high sodium intake (≥ 1,500 mg/day), a long duration of exposure, and the presence of comorbidities. Further studies are required to characterize this iatrogenic risk.Trial registrationPROSPERO CRD42016047086.

Changes in prescribing rates of sodium-containing medications in the UK from 2009 to 2018: a cross-sectional study with interrupted time series analysis

“…We were not able to explore the factors other than age and sex, which might be associated with medication prescription or discontinuation as suggested by other previous publications. 9 10 Furthermore, we were not able to include all dispersible, effervescent or soluble formulations available on prescription. As we aimed to investigate the impact of the publication, we included all equivalent formulations to the drugs included in the original publication.…”

“…The results were later confirmed by a randomised, crossover trial evaluating the effect of effervescent paracetamol on blood pressure 8 and a meta-analysis of eight studies. 9 In 2015, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency (EMA) adopted the findings and have suggested labelling changes to these high sodium-containing medications. With regard to the use of sodium-containing medications, to date, there is only one recent French study that evaluated factors associated with exposure to effervescent drugs, 10 while there is no updated information on prescribing patterns of sodium-containing medicines following the BMJ publication and EMA guideline changes.…”

Drug sodium intake: Warning in cardiovascular diseases treatment

“…The main source of sodium intake is bread, cheese and processed food, which are estimated to contribute up to 75% of daily salt intake [14,15]. Another 20% percent are considered be salt added by the consumer, which leaves 5% coming from water and medicines [14].…”

“…and 2 powder formulations (P1, P2 in Table 3.). Perrin et al (2018) have concluded that daily sodium intake through consumption of high-sodium containing medicines (such as effervescents) higher than 1500 mg, long-term exposure to these medicines, as well as presence of comorbidities (especially hypertension and diabetes mellitus) increase the risk of cardiovascular complications [15]. By this criteria, effervescent granules (Table 2.) and powders ( Table 3.)…”

Evaluation of exposure to effervescent drugs in a large health check-up population in France: a cross-sectional study

“…These high-sodium containing drugs (HSCDs) could theoretically provoke or worsen cardiovascular conditions, especially hypertension, if taken on a regular basis and/or at a high dose. 11 ETs are generally not indicated for patients who require low-salt or normal salt diets (patients with hypertension and those with congestive heart failure), as non-effervescent alternatives are available. 12 A population-based nested case–control study, published by George et al 13 in 2013, showed that patients diagnosed with hypertension or cardiovascular events (non-fatal myocardial infarction, non-fatal stroke or those who died from a vascular cause) were more likely to be prescribed HSCDs.…”