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

Objective Effervescent, soluble, dispersible formulations contain considerable amounts of sodium. In 2013, we previously confirmed the association between sodium-containing medications and cardiovascular risks. This study aimed to determine the changes in the prescribing pattern in clinical practice following this publication.Design A longitudinal cross-sectional study.Setting Primary care in the UK from 2009 to 2018.Participants Prescribing information in The Health Improvement Network (THIN) and Prescription Cost Analysis (PCA) databases in the UK.Outcome measurements Prescription rates per 10 000 inhabitants were calculated using the number of prescriptions or the number of drug-using patients over the total number of inhabitants, and the prescription rates were measured at annual intervals. Prescribing trends from 2009 to 2018 were indexed with yearly data from THIN and PCA. Interrupted time series analysis (ITSA) was conducted with monthly data in THIN.Results From the THIN database, a total of 3 651 419 prescription records from 446 233 patients were included. The prescribing rate of sodium-containing medications changed from 848.3/10 000 inhabitants in 2009 to 571.6/10 000 inhabitants in 2018. The corresponding figures from PCA data were of 631.0/10 000 inhabitants in 2009 and 423.8/10 000 inhabitants in 2018. ITSA showed the prescribing trend reduced significantly during the postpublication period (prescribing rate: slope change=−0.26; 95% CI −0.45 to –0.07; p=0.009; proportion of patients: slope change=−0.22; 95% CI −0.35 to –0.09; p<0.001), but no change in postpublication level from baseline. The prescribing rates for the non-sodium-containing standard formulations were relatively stable over the study period. The reduction in the proportion of patients using sodium-containing medications was only significant in patients over 45 years old.Conclusions The prescribing of sodium-containing medications in the UK primary care has declined significantly during the postpublication period. Changes in the prescribing trends for sodium-containing medications varied across regions of the UK and patient age groups

Impact of ACE Inhibitors and ARBs-related Adverse Drug Reactions Consultations on Patients’ Clinical Outcomes: A Cohort Study in UK Primary Care

Background: Adverse drug reactions (ADRs)related to angiotensin-converting enzyme inhibitor(ACEI) and angiotensin receptor blocker(ARB) may negatively affect patients’ treatment outcomes. There is limited evidence on the impact of ADRs on patients’ outcome in real-world clinical setting. Aim: To investigate the impact of ACEI/ARB-related ADRs consultations in primary care on patients’ clinical outcomes. Design: Propensity score-matched cohort study of ACEI/ARB users during 2004-2019 using IQVIA medical research data. Methods: ACEI/ARB-related ADRs consultations were identified using standardised designated codes in primary care medical records data.Propensity scores were calculated based on comorbidities,concomitant medications,frailty index,polypharmacy,and interval between ACEI/ARB initiation and ADRs date.The outcomes of interest were cardiovascular disease (CVD) events and all-cause mortality.Cox proportional hazard regression models were used to compare the outcomes between ADRs and non-ADRs group. Results: Among 1,471,906 eligible ACEI/ARB users,13,652 patients(0.93%) had ACEI/ARB-related ADRs consultation in primary care. Mean follow-up duration were6.57and4.84years for the CVD primary(n=6,196) and secondary(n=14,238) prevention cohorts,respectively. ACEI/ARB-related ADRs were associated with CVD events and all-cause mortality in both primary(adjusted HR.1.22,95%CI1.05,1.43 and 1.14,95%CI1.01,1.27) and secondary prevention cohort (adjusted HR.1.13,95%CI1.05,1.21 and 1.15,95%CI1.09,1.21).Half (50.19%) patients with ADRs consultation continued to use ACEI/ARB and these patients had a reduced risk of mortality(adjusted HR.0.88,95%CI0.82,0.95) compared to those who discontinued ACEI/ARB. Conclusions: This study provides information on the burden of ADRs on patients and the health system. Patients with ACEI/ARB-related ADRs consultation had an increased risk of subsequent CVD events and mortality,indicating additional monitoring and treatment strategies by healthcare professionals for affected patients are needed to mitigate the risks of adverse clinical outcomes

Statin-related adverse drug reactions in UK primary care consultations: A retrospective cohort study to evaluate the risk of cardiovascular events and all-cause mortality

AIMS: To investigate the risk of cardiovascular disease (CVD) events and all-cause mortality in patients with statin-related adverse drug reaction (ADR) consultation in primary care and examine whether different treatments following the ADR affect subsequent outcomes. METHODS: This was a retrospective cohort study of statin users between 2004 and 2019 using IQVIA Medical Research Data (formally known as the THIN database). Patients with statin-related ADR consultation were matched by propensity score (1:1) to statin users without ADR consultation based on demographics, comorbidities and concomitant medication. Cox proportional hazard regression was used to compare the risk of subsequent CVD event and all-cause mortality, stratified by history of CVD. In the secondary analysis among patients with statin-related ADR, treatment changes within a 1-year period following the ADR were examined and the outcomes were compared between different treatment groups. RESULTS: Among 1 564 687 statin users, 19 035 (1.22%) had a statin-related ADR consultation in primary care. The mean (standard deviation) follow-up time was 6.32 (3.74) years and 5.31 (3.83) years for CVD primary and secondary prevention cohorts, respectively. Statin-related ADR consultation was associated with subsequent CVD events in both cohorts (adjusted hazard ratio [HR] of 1.39 [95% CI 1.23, 1.57] and 1.34 [95% CI 1.25,1.42], respectively). In the secondary analysis among patients with statin-related ADR consultation, we found that (i) continued statin prescription or combination of any statin with additional lipid-lowering treatment (LLT) and (ii) other LLT only were associated with lower risks of CVD event (adjusted HR 0.71 [95% CI 0.64, 0.78] and 0.75 [95% CI 0.62, 0.92], respectively) and all-cause mortality (adjusted HR 0.46 [95% CI 0.42, 0.50] and 0.52 [95% CI, 0.43, 0.64], respectively), compared to discontinuation of all LLT. CONCLUSION: Statin-related ADR was associated with an increased risk of subsequent CVD event, indicating that these patients should be monitored more closely. Continued lipid-lowering medication is of importance to protect against CVD events and mortality

Effects of Phosphodiesterase-5 Inhibitors in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Chronic obstructive pulmonary disease (COPD) is a major burden of healthcare worldwide. We aimed to determine the effects of PDE-5 inhibitors on clinical outcomes and haemodynamic parameters in patients with COPD. A PROSPERO-registered systematic review and meta-analysis (identification number CRD42021227578) were performed to analyse the effects of PDE-5 inhibitors in patients with COPD. Data were sourced from MEDLINE, EMBASE, Cochrane Register of Controlled Trials and "ClinicalTrials.gov." Randomised controlled trials (RCTs) comparing PDE-5 inhibitors with control in patients with COPD were included. Quality assessment was carried out using the Cochrane Collaboration's tool for assessing the risk of bias in randomised trials. The pooled mean difference of 6-minute walk distance (6MWD) and mean pulmonary arterial pressure based on inverse variance estimation were analysed with a fixed-effect model or random-effects model meta-analysis. Nine RCTs involving 414 patients were included in the review. There was no significant difference in 6MWD (mean difference = 22.06 metres, 95% confidence interval (CI), -5.80 to 49.91). However, there was a statistically significant difference between PDE-5 inhibitor and control groups in mean pulmonary artery pressure (mean difference = -3.83 mmHg, 95% CI, -5.93 to -1.74). Headaches were the most common adverse event, occurring significantly in the PDE-5 inhibitor intervention group (odds ratio 3.83, 95% CI, 1.49 to 9.86). This systematic review indicates that PDE-5 inhibitors do not improve exercise capacity despite some possible improvements in haemodynamic parameters in COPD patients

Effect of statin treatment on the risk of cancer in patients with heart failure:A target trial emulation study

PURPOSE: A recent observational study suggested statins could reduce cancer diagnosis in patients with heart failure (HF). The findings need to be validated using robust epidemiological methods. This study aimed to evaluate the effect of statin treatment on the risk of cancer in patients with HF.METHODS: We conducted two target trial emulations using primary care data from IQVIA Medical Research Database-UK (2000 to 2019) with a clone-censor-weight design. The first emulated trial addressed the treatment initiation effect: initiating within 1 year versus not initiating a statin after the HF diagnosis. The second emulated trial addressed the cumulative exposure effect: continuing a statin for ≤3 years, 3-6 years, and &gt;6 years after initiation. The study outcomes were any incident cancer and site-specific cancer diagnoses. Weighted pooled logistic regression models were used to estimate 10-year risk ratios (RR). 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping.RESULTS: The first emulated trial showed that, compared to no statin, statins did not reduce the cancer risk in patients with HF (RR, 1.05; 95% CI, 0.94-1.15). The second emulated trial showed that, compared to treatment ≤3 years, statins with longer durations did not reduce the cancer risk (3-6 years: RR, 0.94; 95% CI, 0.70-1.33. &gt;6 years: RR, 0.97; 95% CI, 0.79-1.26). No significant risk difference was observed on any site-specific cancer diagnoses.CONCLUSIONS: The results from the target trial emulations suggest that statin treatment is not associated with cancer risk in patients with HF.</p

Effect of statin treatment on the risk of cancer in patients with heart failure:A target trial emulation study

PURPOSE: A recent observational study suggested statins could reduce cancer diagnosis in patients with heart failure (HF). The findings need to be validated using robust epidemiological methods. This study aimed to evaluate the effect of statin treatment on the risk of cancer in patients with HF.METHODS: We conducted two target trial emulations using primary care data from IQVIA Medical Research Database-UK (2000 to 2019) with a clone-censor-weight design. The first emulated trial addressed the treatment initiation effect: initiating within 1 year versus not initiating a statin after the HF diagnosis. The second emulated trial addressed the cumulative exposure effect: continuing a statin for ≤3 years, 3-6 years, and &gt;6 years after initiation. The study outcomes were any incident cancer and site-specific cancer diagnoses. Weighted pooled logistic regression models were used to estimate 10-year risk ratios (RR). 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping.RESULTS: The first emulated trial showed that, compared to no statin, statins did not reduce the cancer risk in patients with HF (RR, 1.05; 95% CI, 0.94-1.15). The second emulated trial showed that, compared to treatment ≤3 years, statins with longer durations did not reduce the cancer risk (3-6 years: RR, 0.94; 95% CI, 0.70-1.33. &gt;6 years: RR, 0.97; 95% CI, 0.79-1.26). No significant risk difference was observed on any site-specific cancer diagnoses.CONCLUSIONS: The results from the target trial emulations suggest that statin treatment is not associated with cancer risk in patients with HF.</p

Association between gout and atrial fibrillation: A meta-analysis of observational studies

Background: Gout is a systemic inflammatory arthritis characterized by the deposition of monosodium urate crystals due to hyperuricemia. Previous studies have explored the link between gout and atrial fibrillation (AF). Given the increasing prevalence and incidence of gout, there is a need to quantify the relationship between gout and the risk of AF. Therefore, we conducted a systematic review and meta-analysis on this topic. Methods: PubMed and Embase were searched for studies that reported the association between gout and AF using the following search term: (‘Gout’ and ‘Arrhythmia’). The search period was from the start of the database to 3rd August 2018 with no language restrictions. Results: A total of 75 and 22 articles were retrieved from PubMed and Embase, respectively. Of these, four observational studies (three cohort studies, one case-control study) including 659,094 patients were included. Our meta-analysis demonstrated that gout was significantly associated with increased risk of AF (adjusted hazard ratio: 1.31; 95% confidence interval: 1.00-1.70; P = 0.05; I2 = 99%) after adjusting for significant comorbidities and confounders. Conclusions: Our meta-analysis confirms the significant relationship between gout and AF. More data are needed to determine whether this risk can be adequately reduced by urate-lowering therapy

Impact of ACEIs and ARBs-related adverse drug reaction on patients’ clinical outcomes:a cohort study in UK primary care

Background: Adverse drug reaction (ADR) related to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may negatively affect patients’ treatment outcomes. Aim: To investigate the impact of ACEIs/ARBs-related ADR consultation on cardiovascular disease (CVD) events and all-cause mortality. Design and setting: Propensity score-matched cohort study of ACEIs/ ARBs between 2004 and 2019 using UK IQVIA medical research data. Method: ADR consultations were identified using standardised designated codes. Propensity scores were calculated based on comorbidities, concomitant medications, frailty, and polypharmacy. Cox’s proportional hazard regression model was used to compare the outcomes between patients in ADR and non-ADR groups. In the secondary analysis, treatment-pattern changes following the ADR were examined and the subsequent outcomes were compared. Results: Among 1 471 906 eligible users of ACEIs/ARBs, 13 652 (0.93%) patients had ACEIs/ARBs-related ADR consultation in primary care. Patients with ACEIs/ARBs-related ADR consultation had an increased risk of subsequent CVD events and all-cause mortality in both primary prevention (CVD events: adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] = 1.05 to 1.43; all-cause mortality: aHR 1.14, 95% CI = 1.01 to 1.27) and secondary prevention cohorts (CVD events: aHR 1.13, 95% CI = 1.05 to 1.21; all-cause mortality: aHR 1.15, 95% CI = 1.09 to 1.21). Half (50.19%) of patients with ADR continued to use ACEIs/ARBs, and these patients had a reduced risk of mortality (aHR 0.88, 95% CI = 0.82 to 0.95) compared with those who discontinued using ACEIs/ARBs.Conclusion: This study provides information on the burden of ADR on patients and the health system. The findings call for additional monitoring and treatment strategies for patients affected by ADR to mitigate the risks of adverse clinical outcomes.</p

Impact of beta-blockers on mortality and cardiovascular disease outcomes in patients with obstructive sleep apnoea: a population-based cohort study in target trial emulation frameworkResearch in context

Summary: Background: There is no real-world evidence regarding the association between beta-blocker use and mortality or cardiovascular outcomes in patients with obstructive sleep apnoea (OSA). We aimed to investigate the impact of beta-blocker use on all-cause mortality and cardiovascular diseases (CVDs) in patients with OSA. Methods: We conducted a target trial emulation study of 37,581 patients with newly diagnosed OSA from 1st January 2000 to 30th November 2021 using the IMRD-UK database (formerly known as the THIN database). We compared the treatment strategies of initiating beta-blocker treatment within one year versus non-beta-blocker treatment through the method of clone-censor-weight. Covariates, including patients’ demographics, lifestyle, comorbidities, and recent medications, were measured and controlled. Patients were followed up for all-cause mortality or composite CVD outcomes (angina, myocardial infarction, stroke/transient ischaemic attack, heart failure, or atrial fibrillation). We estimated the five-year absolute risks, risk differences and risk ratio with 95% confidence intervals (CIs) with standardised, weighted pooled logistic regression, which is a discrete-time hazard model for survival analysis. Several sensitivity analyses were performed, including multiple imputation addressing the missing data. Findings: The median follow-up time was 4.1 (interquartile range, 1.9–7.8) years. The five-year absolute risk of all-cause mortality and CVD outcomes were 4.9% (95% CI, 3.8–6.0) and 13.0% (95% CI, 11.4–15.0) among beta-blocker users, and 4.0% (95% CI, 3.8–4.2) and 9.4% (95% CI, 9.1–9.7) among non-beta-blocker users, respectively. The five-year absolute risk difference and risk ratio between the two groups for all-cause mortality and CVD outcomes were 0.9% (95% CI, −0.2 to 2.1) and 1.22 (95% CI, 0.96–1.54), and 3.5% (95% CI, 2.1–5.5) and 1.37 (95% CI, 1.22–1.62), respectively. Findings were consistent across the sensitivity analyses. Interpretation: Beta-blocker treatment was associated with an increased risk of CVD and a trend for an increased risk of mortality among patients with OSA. Further studies are needed to confirm our findings. Funding: Innovation and Technology Commission of the Hong Kong Special Administration Region Government