Abstract P135: Varenicline and the Risk of Adverse Cardiovascular Events: A Population-Based Cohort Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Kristian B Filion ◽  
Sophie Dell'Aniello ◽  
Maria Eberg ◽  
Christel Renoux ◽  
Stella S Daskalopoulou ◽  
...  

Background: Clinical trial results suggest that varenicline is the most efficacious smoking cessation therapy. However, its cardiovascular safety is controversial, with recent meta-analyses providing conflicting results. Our objective was to compare the effect of varenicline to that of bupropion on the risk of cardiovascular events. Methods: We conducted a population-based cohort study of new users of varenicline or bupropion using data extracted from the UK’s Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics. Our primary endpoint was a composite of myocardial infarction, coronary revascularization, stroke, and all-cause mortality. An ‘as-treated’ analysis with a Cox proportional hazards model was used, with patients censored 7 days after the end of their last prescription or upon switching smoking cessation drugs. In secondary analyses, we compared varenicline and bupropion to nicotine replacement therapy (NRT) in pairwise comparisons. All analyses used high-dimensional propensity scores to adjust for potential confounding. Results: Our primary cohort included 90,522 varenicline users and 12,640 bupropion users. The mean age was 44 years, and 48% were men. The mean treatment duration was 45 days. A total of 128 events occurred among varenicline users, and 15 occurred among bupropion users. Although estimates suggest that varenicline may modestly increase the risk of cardiovascular events compared to bupropion, they were accompanied by wide 95% CIs (Table). Both varenicline and bupropion users had significantly lower risks of cardiovascular events than NRT users (Table). Conclusions: While we cannot exclude a modestly increased risk of cardiovascular events with varenicline relative to bupropion, such events remain rare, and both varenicline and bupropion are associated with a decreased risk of cardiovascular events compared with NRT. The long-term benefits obtained due to the increased smoking abstinence with varenicline likely outweigh any increased cardiovascular risk.

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Michikazu Nakai ◽  
Makoto Watanabe ◽  
Kunihiro Nishimura ◽  
Misa Takegami ◽  
Yoshihiro Kokubo ◽  
...  

Objective: The positive relation between body mass index (BMI) and risk of incident hypertension (HT) has been reported mainly in the Western subjects with high BMI. However, there are a few reports in the Asian with relatively lower BMI. This study investigated the relation of BMI with risk of incident HT in the population-based prospective cohort study of Japan, the Suita study. Methods: Participants who had no HT at baseline (1,591 men and 1,973 women) aged 30-84 years were included in this study. BMI categories were defined as following: underweight (BMI<18.5), normal (18.5≤BMI<25.0), and overweight (BMI ≥ 25.0). The Cox proportional hazards model was used to estimate hazard ratios (HRs) of BMI categories for incident HT by sex. HRs were adjusted for age, cigarette smoking and alcohol drinking. The HRs according to quartiles of BMI were also estimated, using the lowest quartile of BMI as a reference. Results: During median follow-up of 7.2 years, 1,325 participants (640 men and 685 women) developed HT. The HR (95% CI) of 1kg/m2 increment of BMI for HT in men and women was 1.08 (1.05-1.11) and 1.10 (1.07-1.12), respectively. When we set a normal BMI as a reference, HR of overweight BMI in men and women was 1.37 (1.13-1.67) and 1.45 (1.18-1.77), whereas HR of underweight BMI in men and women was 0.63 (0.45-0.90) and 0.60 (0.45-0.80), respectively. In addition, compared to the lowest quartile, HR of the highest quartile of BMI in men and women was 1.67 (1.33-2.10, trend p<0.001) and 2.10 (1.67-2.64, trend p<0.001), respectively. Conclusion: In this study, we showed that higher BMI was associated with increased risk of hypertension in both Japanese men and women.


2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Lasse Wegener Lund ◽  
Jeanette Falck Winther ◽  
Luise Cederkvist ◽  
Catherine Rechnitzer ◽  
Susanne Oksbjerg Dalton ◽  
...  

Abstract Siblings of children with cancer experience severe stress early in life. Most studies of mental health problems in these siblings are limited by being small, cross-sectional, or self-reporting. In a population-based cohort study, we investigated the risk for antidepressant use by linking several nationwide, population-based registries comparing 6644 siblings of children diagnosed with cancer from 1991-2009 with 128 436 population-based sibling comparisons using the Cox proportional hazards model. Irrespective of cancer type, no increased risk of antidepressant use in siblings of children with cancer was found (hazard ratio = 1.00, 95% confidence interval = 0.91 to 1.11). However, data suggested that siblings being young at cancer diagnosis had an increased risk (2-sided Ptrend = .01). Interaction analyses showed no modifying effect of parental socioeconomic position or antidepressant use. Findings from this study with a very low risk of bias are reassuring and important for families facing childhood cancer and for clinicians counseling these families.


2009 ◽  
Vol 27 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Hanne Stensheim ◽  
Bjørn Møller ◽  
Tini van Dijk ◽  
Sophie D. Fosså

Purpose To assess if cancers diagnosed during pregnancy or lactation are associated with increased risk of cause-specific death. Patients and Methods In this population-based cohort study using data from the Cancer Registry and the Medical Birth Registry of Norway, 42,511 women, age 16 to 49 years and diagnosed with cancer from 1967 to 2002, were eligible. They were grouped as not pregnant (reference), pregnant, or lactating at diagnosis. Cause-specific survival for all sites combined, and for the most frequent malignancies, was investigated using a Cox proportional hazards model. An additional analysis with time-dependent covariates was performed for comparison of women with and without a postcancer pregnancy. The multivariate analyses were adjusted for age at diagnosis, extent of disease, and diagnostic periods. Results For all sites combined, no intergroup differences in cause-specific death were seen, with hazard ratio (HR) of 1.03 (95% CI, 0.86 to 1.22) and HR 1.02 (95% CI, 0.86 to 1.22) for the pregnant and lactating groups, respectively. Patients with breast (HR, 1.95; 95% CI, 1.36 to 2.78) and ovarian cancer (HR, 2.23; 95% CI, 1.05 to 4.73) diagnosed during lactation had an increased risk of cause-specific death. Diagnosis of malignant melanoma during pregnancy slightly increased this risk. For all sites combined, the risk of cause-specific death was significantly decreased for women who had postcancer pregnancies. Conclusion In general, the diagnosis of most cancer types during pregnancy or lactation does not increase the risk of cause-specific death. Breast and ovarian cancer diagnosed during lactation represents an exception. We confirmed the “healthy mother effect” for women with a postcancer pregnancy.


Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 132-139
Author(s):  
Ruth E Costello ◽  
Belay B Yimer ◽  
Polly Roads ◽  
Meghna Jani ◽  
William G Dixon

Abstract Objectives Patients with RA are frequently treated with glucocorticoids (GCs), but evidence is conflicting about whether GCs are associated with hypertension. The aim of this study was to determine whether GCs are associated with incident hypertension in patients with RA. Methods A retrospective cohort of patients with incident RA and without hypertension was identified from UK primary care electronic medical records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use, dose and cumulative dose, with a 3 month attribution window. Hypertension was identified through either: blood pressure measurements &gt;140/90 mmHg, or antihypertensive prescriptions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards regression models were fitted to determine whether there was an association between GC use and incident hypertension. Results There were 17 760 patients in the cohort. A total of 7421 (42%) were prescribed GCs during follow-up. The incident rate of hypertension was 64.1 per 1000 person years (95% CI: 62.5, 65.7). The Cox proportional hazards model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio 1.17; 95% CI: 1.10, 1.24). When categorized by dose, only doses above 7.5 mg were significantly associated with hypertension. Cumulative dose did not indicate a clear pattern. Conclusion Recent GC use was associated with incident hypertension in patients with RA, in particular doses ≥7.5 mg were associated with hypertension. Clinicians need to consider cardiovascular risk when prescribing GCs, and ensure blood pressure is regularly monitored and treated where necessary.


2021 ◽  
Vol 9 (2) ◽  
pp. e002496
Author(s):  
Wajd Alkabbani ◽  
Arsene Zongo ◽  
Jasjeet K Minhas-Sandhu ◽  
Dean T Eurich ◽  
Baiju R Shah ◽  
...  

IntroductionTo assess the comparative effectiveness and safety of renal-related outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2-i) initiation among patients with type 2 diabetes using real-world data.Research design and methodsWe conducted a population‐based cohort study using administrative healthcare data from Alberta (AB), Canada and primary care data from the Clinical Practice Research Datalink (CPRD), UK. From a cohort of new metformin users, we identified initiators of a SGLT2-i or dipeptidyl peptidase-4 inhibitor (DPP4-i) between January 1, 2014 and March 30, 2018 (AB) or between January 1, 2013 and November 29, 2018 (CPRD). Initiators of an SGLT2-i or DPP4-i were followed until death, disenrolment, therapy discontinuation, or study end date. The effectiveness outcome was renal disease progression, defined as a composite of new-onset macroalbuminuria, serum creatinine doubling with estimated glomerular filtration rate of ≤45 mL/min/1.73 m2, renal replacement therapy, hospital admission or death from renal causes. The safety outcome was hospitalization due to acute kidney injury (AKI). We adjusted for confounding using high-dimensional propensity score matching and estimated HRs using Cox proportional hazards regression. Aggregate data from each database were combined by random-effects meta‐analysis.ResultsAmong the 29 465 included patients (20 564 AB, 8901 CPRD), 37.5% were new SGLT2-i users in AB and 21.3% in CPRD. Compared with DPP4 initiators, SGLT2-i initiators were associated with a reduced risk of renal disease progression (pooled HR 0.79, 95% CI 0.62 to 1.00); however, there was no significant difference in the risk of AKI (pooled HR 0.89, 95% CI 0.58 to 1.36). These findings were consistent with other exposure definitions and antidiabetic comparators.ConclusionsOur findings support a renoprotective effect of SGLT2-i without an increased risk of AKI, compared with clinically relevant active comparators.


2021 ◽  
Vol 30 ◽  
Author(s):  
H. Wang ◽  
H. He ◽  
M. Miao ◽  
Y. Yu ◽  
H. Liu ◽  
...  

Abstract Aims Maternal migraine may contribute to mental heath problems in offspring but empirical evidence has been available only for bipolar disorders. Our objective was to examine the association between maternal migraine and the risk of any and specific psychiatric disorders in offspring. Methods This population-based cohort study used individual-level linked Danish national health registers. Participants were all live-born singletons in Denmark during 1978–2012 (n = 2 069 785). Follow-up began at birth and continued until the onset of a psychiatric disorder, death, emigration or 31 December 2016, whichever came first. Cox proportional hazards model was employed to calculate the hazard ratios (HRs) of psychiatric disorders. Results Maternal migraine was associated with a 26% increased risk of any psychiatric disorders in offspring [HR, 1.26; 95% confidence interval (CI), 1.22–1.30]. Increased rates of psychiatric disorders were seen in all age groups from childhood to early adulthood. Increased rates were also observed for most of the specific psychiatric disorders, in particular, mood disorders (HR, 1.53; 95% CI, 1.39–1.67), neurotic, stress-related and somatoform disorders (HR, 1.44; 95% CI, 1.37–1.52) and specific personality disorders (HR, 1.47; 95% CI, 1.27–1.70), but not for intellectual disability (HR, 0.84; 95% CI, 0.71–1.00) or eating disorders (HR, 1.10; 95% CI, 0.93–1.29). The highest risk was seen in the offspring of mothers with migraine and comorbid psychiatric disorders (HR, 2.13; 95% CI, 1.99–2.28). Conclusions Maternal migraine was associated with increased risks of a broad spectrum of psychiatric disorders in offspring. Given the high prevalence of migraine, our findings highlight the importance of better management of maternal migraine at childbearing ages for early prevention of psychiatric disorders in offspring.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Thomas Inns ◽  
Kate M. Fleming ◽  
Miren Iturriza-Gomara ◽  
Daniel Hungerford

Abstract Background Rotavirus infection has been proposed as a risk factor for coeliac disease (CD) and type 1 diabetes (T1D). The UK introduced infant rotavirus vaccination in 2013. We have previously shown that rotavirus vaccination can have beneficial off-target effects on syndromes, such as hospitalised seizures. We therefore investigated whether rotavirus vaccination prevents CD and T1D in the UK. Methods A cohort study of children born between 2010 and 2015 was conducted using primary care records from the Clinical Practice Research Datalink. Children were followed up from 6 months to 7 years old, with censoring for outcome, death or leaving the practice. CD was defined as diagnosis of CD or the prescription of gluten-free goods. T1D was defined as a T1D diagnosis. The exposure was rotavirus vaccination, defined as one or more doses. Mixed-effects Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs). Models were adjusted for potential confounders and included random intercepts for general practices. Results There were 880,629 children in the cohort (48.8% female). A total of 343,113 (39.0%) participants received rotavirus vaccine; among those born after the introduction of rotavirus vaccination, 93.4% were vaccinated. Study participants contributed 4,388,355 person-years, with median follow-up 5.66 person-years. There were 1657 CD cases, an incidence of 38.0 cases per 100,000 person-years. Compared with unvaccinated children, the adjusted HR for a CD was 1.05 (95% CI 0.86–1.28) for vaccinated children. Females had a 40% higher hazard than males. T1D was recorded for 733 participants, an incidence of 17.1 cases per 100,000 person-years. In adjusted analysis, rotavirus vaccination was not associated with risk of T1D (HR = 0.89, 95% CI 0.68–1.19). Conclusions Rotavirus vaccination has reduced diarrhoeal disease morbidity and mortality substantial since licencing in 2006. Our finding from this large cohort study did not provide evidence that rotavirus vaccination prevents CD or T1D, nor is it associated with increased risk, delivering further evidence of rotavirus vaccine safety.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lisa M. Lix ◽  
Shamsia Sobhan ◽  
Audray St-Jean ◽  
Jean-Marc Daigle ◽  
Anat Fisher ◽  
...  

Abstract Background Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data. Methods Administrative health records were from an existing multi-database cohort study about sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications. Data were from 2013 to 2018 for five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD). The cardiovascular mortality algorithm was based on in-hospital cardiovascular deaths identified from diagnosis codes and select out-of-hospital deaths. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for the cardiovascular mortality algorithm using vital statistics registrations as the reference standard. Overall and stratified estimates and 95% confidence intervals (CIs) were computed; the latter were produced by site, location of death, sex, and age. Results The cohort included 20,607 individuals (58.3% male; 77.2% ≥70 years). When compared to vital statistics registrations, the cardiovascular mortality algorithm had overall sensitivity of 64.8% (95% CI 63.6, 66.0); site-specific estimates ranged from 54.8 to 87.3%. Overall specificity was 74.9% (95% CI 74.1, 75.6) and overall PPV was 54.5% (95% CI 53.7, 55.3), while site-specific PPV ranged from 33.9 to 72.8%. The cardiovascular mortality algorithm had sensitivity of 57.1% (95% CI 55.4, 58.8) for in-hospital deaths and 72.3% (95% CI 70.8, 73.9) for out-of-hospital deaths; specificity was 88.8% (95% CI 88.1, 89.5) for in-hospital deaths and 58.5% (95% CI 57.3, 59.7) for out-of-hospital deaths. Conclusions A cardiovascular mortality algorithm applied to administrative health records had moderate validity when compared to vital statistics data. Substantial variation existed across study sites representing different geographic locations and two healthcare systems. These variations may reflect different diagnostic coding practices and healthcare utilization patterns.


2014 ◽  
Vol 112 (08) ◽  
pp. 255-263 ◽  
Author(s):  
Alexander T. Cohen ◽  
Luke Bamber ◽  
Stephan Rietbrock ◽  
Carlos Martinez

SummaryContemporary data from population studies on the incidence and complications of venous thromboembolism (VTE) are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The cohort was identified from all patients in the UK Clinical Practice Research Datalink (CPRD) with additional linked information on hospitalisation and cause of death. Between 2001 and 2011, patients with first VTE were identified and the subset without active cancer-related VTE observed for up to 10 years for recurrent VTE. The 10-year cumulative incidence rates (CIR) were derived with adjustment for mortality as a competing risk event. A total of 35,373 first VTE events (12,073 provoked, 16,708 unprovoked and 6592 active cancer-associated VTE) among 26.9 million person-years of observation were identified. The overall incidence rate (IR) of VTE was 131.5 (95% CI, 130.2–132.9) per 100,000 person-years and 107.0 (95% CI, 105.8–108.2) after excluding cancer-associated VTE. DVT was more common in the young and PE was more common in the elderly. VTE recurrence occurred in 3671 (CIR 25.2%). The IR for recurrence peaked in the first six months at around 11 per 100 person years. It levelled out after three years and then remained at around 2 per 100 person years from year 4–10 of follow-up. The IRs for recurrences were particularly high in young men. In conclusion, VTE is common and associated with high recurrence rates. Effort is required to prevent VTE and to reduce recurrences.


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