Association between cardiovascular events and sodium-containing effervescent, dispersible, and soluble drugs: nested case-control study

BMJ. 2013 Nov 26:347:f6954. doi: 10.1136/bmj.f6954.


Objective: To determine whether patients taking formulations of drugs that contain sodium have a higher incidence of cardiovascular events compared with patients on non-sodium formulations of the same drugs.

Design: Nested case-control study.

Setting: UK Primary Care Patients registered on the Clinical Practice Research Datalink (CPRD).

Participants: All patients aged 18 or over who were prescribed at least two prescriptions of sodium-containing formulations or matched standard formulations of the same drug between January 1987 and December 2010.

Main outcome measures: Composite primary outcome of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death. We performed 1:1 incidence density sampling matched controls using the UK Clinical Practice Research Datalink (CPRD). For the secondary analyses, cases were patients with the individual components of the primary study composite endpoint of hypertension, incident heart failure, and all cause mortality.

Results: 1,292,337 patients were included in the study cohort. Mean follow-up time was 7.23 years. A total of 61,072 patients with an incident cardiovascular event were matched with controls. For the primary endpoint of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death the adjusted odds ratio for exposure to sodium-containing drugs was 1.16 (95% confidence interval 1.12 to 1.21). The adjusted odds ratios for the secondary endpoints were 1.22 (1.16 to 1.29) for incident non-fatal stroke, 1.28 (1.23 to 1.33) for all cause mortality, 7.18 (6.74 to 7.65) for hypertension, 0.98 (0.93 to 1.04) for heart failure, 0.94 (0.88 to 1.00) for incident non-fatal myocardial infarction, and 0.70 (0.31 to 1.59) for vascular death. The median time from date of first prescription (that is, date of entry into cohort) to first event was 3.92 years.

Conclusions: Exposure to sodium-containing formulations of effervescent, dispersible, and soluble medicines was associated with significantly increased odds of adverse cardiovascular events compared with standard formulations of those same drugs. Sodium-containing formulations should be prescribed with caution only if the perceived benefits outweigh these risks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Humans
  • Incidence
  • Logistic Models
  • Male
  • Middle Aged
  • Nonprescription Drugs / adverse effects
  • Nonprescription Drugs / chemistry*
  • Sodium / administration & dosage
  • Sodium / adverse effects*
  • United Kingdom / epidemiology


  • Nonprescription Drugs
  • Sodium