Dataset Information

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

ABSTRACT:

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.

SUBMITTER: George J

PROVIDER: S-EPMC3898660 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description: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.

Project description:Soluble TNF-like weak inducer of apoptosis (sTWEAK) is a proinflammatory cytokine belonging to the TNF superfamily. sTWEAK concentrations have been associated with the presence of CKD and cardiovascular disease (CVD). We hypothesized that sTWEAK levels may relate to a higher prevalence of atherosclerotic plaques, vascular calcification, and cardiovascular outcomes observed in patients with CKD.A 4-year prospective, multicenter, longitudinal study was conducted in 1058 patients with CKD stages 3-5D (mean age =58±13 years old; 665 men) but without any history of CVD from the NEFRONA Study (a study design on the prevalence of surrogate markers of CVD). Ankle-brachial index and B-mode ultrasound were performed to detect the presence of carotid and/or femoral atherosclerotic plaques together with biochemical measurements and sTWEAK assessment. Patients were followed for cardiovascular outcomes (follow-up of 3.13±1.15 years).Patients with more advanced CKD had lower sTWEAK levels. sTWEAK concentrations were independently and negatively associated with carotid intima-media thickness. sTWEAK levels were lower in patients with carotid atherosclerotic plaques but not in those with femoral plaques. After adjustment by confounders, the odds ratio (OR) for presenting carotid atherosclerotic plaques in patients in the lowest versus highest tertile of sTWEAK was 4.18 (95% confidence interval [95% CI], 2.89 to 6.08; P<0.001). Furthermore, sTWEAK levels were lower in patients with calcified carotid atherosclerotic plaques. The OR for presenting calcified carotid plaques was 1.77 (95% CI, 1.06 to 2.93; P=0.02) after multivariable adjustment. After the follow-up, 41 fatal and 68 nonfatal cardiovascular events occurred. In a Cox model, after controlling for potential confounding factors, patients in the lowest tertile of sTWEAK concentrations had a higher risk of fatal and nonfatal cardiovascular events (hazard ratio [HR], 2.40; 95% CI, 1.33 to 4.33; P=0.004) and cardiovascular mortality (HR, 2.67; 95% CI, 1.05 to 6.76; P=0.04).Low sTWEAK levels were associated with the presence of carotid atherosclerotic plaques in patients with CKD. Additionally, lower sTWEAK levels were associated with a higher risk of cardiovascular morbidity and mortality.