Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study.

OBJECTIVES: Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol. METHODS: We conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (01/04/1997-30/11/2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction (MI), neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression, were estimated. RESULTS: From 01/04/1997-30/11/2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis (mean age 63.9 (SD 14.7) years, 78.2% male). One quarter (26%, 95% CI 25% to 27%) were prescribed ≥1 potentially interacting medicines, most commonly statins (21%, 95% CI 20% to 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and MI were associated with more comorbidities and more severe CKD. CONCLUSION: People were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol.

Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink.

OBJECTIVES: To determine the risk of adverse events associated with colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis when initiating allopurinol for gout. METHODS: We conducted two matched retrospective cohort studies in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with (1) colchicine or (2) NSAID prophylaxis were compared with those initiating without prophylaxis, individually matched by age, sex and propensity to receive the relevant prophylaxis. Weighted Cox proportional hazards models investigated associations between colchicine/NSAID and specified adverse events. RESULTS: 13 945 individuals prescribed colchicine were matched to 13 945 with no prophylaxis and 25 980 prescribed NSAID to 25 980 with no prophylaxis. Adverse event incidence rates were <200/10 000 patient-years except diarrhoea (784.4; 95% CI 694.0 to 886.5) and nausea (208.1; 95% CI 165.4 to 261.7) for colchicine and angina for NSAID (466.6; 95% CI 417.2 to 521.8). Diarrhoea (HR 2.22; 95% CI 1.83 to 2.69), myocardial infarction (MI) (1.55; 95% CI 1.10, 2.17), neuropathy (4.75; 95% CI 1.20 to 18.76), myalgia (2.64; 95% CI 1.45 to 4.81), bone marrow suppression (3.29; 95% CI 1.43 to 7.58) and any adverse event (1.91, 95% CI 1.65 to 2.20) were more common with colchicine than no prophylaxis, but not nausea/vomiting (1.34; 95% CI 0.97 to 1.85). Angina (1.60; 95% CI 1.37 to 1.86), acute kidney injury (1.56; 95% CI 1.20 to 2.03), MI (1.89; 95% CI 1.44 to 2.48), peptic ulcer disease (1.67; 95% CI 1.14 to 2.44) and any adverse event (1.63; 95% CI 1.44 to 1.85) were more common with NSAID than without. CONCLUSIONS: Adverse events were more common when allopurinol was initiated with prophylaxis, particularly diarrhoea with colchicine. Other events were uncommon, providing reassurance for patients and clinicians to enable shared decision-making.

Impact of Frailty on Emergency Department Encounters for Cardiovascular Disease: A Retrospective Cohort Study.

Data are limited on whether the causes of emergency department (ED) encounters for cardiovascular diseases (CVDs) and associated clinical outcomes vary by frailty status. Using the United States Nationwide ED Sample, selected CVD encounters (acute myocardial infarction [AMI], ischemic stroke, atrial fibrillation [AF], heart failure [HF], pulmonary embolism, cardiac arrest, and hemorrhagic stroke) were stratified by hospital frailty risk score (HFRS). Logistic regression was used to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of ED mortality among the different frailty groups. A total of 8,577,028 selected CVD ED encounters were included. A total of 5,120,843 (59.7%) had a low HFRS (<5), 3,041,699 (35.5%) had an intermediate HFRS (5 to 15), and 414,485 (4.8%) had a high HFRS (>15). Ischemic stroke was the most common reason for the encounter in the high HFRS group (66.9%), followed by hemorrhagic stroke (11.7%) and AMI (7.2%). For the low HFRS group, AF was the most common reason for the encounter (30.2%), followed by AMI (23.6%) and HF (16.8%). Compared with the low-risk group, high-risk patients had a decreased ED mortality and an increased overall mortality across most CVD encounters (p <0.001). The strongest association with overall mortality was observed among patients with a high HFRS admitted for AF (aOR 27.14, 95% CI 25.03 to 29.43) and HF (aOR 13.71, 95% CI 12.95 to 14.51) compared with their low-risk counterparts. In conclusion, patients presenting to the ED with acute CVD have a significant frailty burden, with different patterns of CVD according to frailty status. Frailty is associated with an increased all-cause mortality in patients for most CVD encounters.

Association of Frailty Status on the Causes and Outcomes of Patients Admitted With Cardiovascular Disease.

Data are limited about the contemporary association between frailty and the causes and outcomes of patients admitted with cardiovascular diseases (CVD). Using the US National Inpatient Sample, CVD admissions of interest (acute myocardial infarction, ischemic stroke, atrial fibrillation (AF), heart failure, pulmonary embolism, cardiac arrest, and hemorrhagic stroke) were stratified by Hospital Frailty Risk Score (HFRS). Logistic regression was used to determine adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of in-hospital mortality among different groups with frailty. The study included 9,317,398 hospitalizations. Of these, 5,573,033 (59.8%) had a low HFRS (<5); 3,422,700 (36.7%) had an intermediate HFRS (5 to 15); and 321,665 (3.5%) had a high HFRS (>15). Ischemic stroke was the most common admission for the groups with high risk (75.4%), whereas acute myocardial infarction was the most common admission for the group with low risk (36.9%). Compared with the group with low risk, patients with high risk had increased mortality across the most CVD admissions, except in patients admitted for cardiac arrest and hemorrhagic stroke (p <0.001). The strongest association with all-cause mortality was shown among patients with high risk admitted for AF (aOR 6.75, 95% CI 6.51 to 7.00, and aOR 17.69, 95% CI 16.08 to 19.45) compared with their counterparts with low risk. In conclusion, patients with CVD admissions have varying frailty risk according to cardiovascular cause of admission, with ischemic stroke being the most common among groups with frailty and high risk. Increased frailty is associated with all-cause mortality in patients with most CVD admissions, except for cardiac arrest and hemorrhagic stroke, with the strongest association seen in patients admitted with AF.

Mortality Among Patients With Polymyalgia Rheumatica: A Retrospective Cohort Study.

OBJECTIVE: To determine whether a diagnosis of polymyalgia rheumatica (PMR) is associated with premature mortality. METHODS: We extracted anonymized electronic medical records of patients ages >40 years who were eligible for linkage with the Office for National Statistics Death Registration data set, from the Clinical Practice Research Datalink from 1990 to 2016. Patients with PMR were individually matched, by age, sex, and registered general practice, with up to 5 controls without PMR. The total number and proportion of deaths and mortality rates were calculated. The mortality rate ratio (MRR) with 95% confidence interval (95% CI), adjusted for age, sex, region, smoking status, body mass index, and alcohol consumption, was calculated using Poisson regression. The 20 most common causes of death were tabulated. RESULTS: A total of 18,943 patients with PMR were matched to 87,801 controls. The mean ± SD follow-up after date of diagnosis was 8.0 ± 4.4 years in patients with PMR and 7.9 ± 4.6 years in controls. PMR was not associated with an increase in the risk of death (adjusted MRR 1.00 [95% CI 0.97-1.03]) compared to matched controls. Causes of death were broadly similar between patients with PMR and controls, although patients with PMR were slightly more likely to have a vascular cause of death recorded (24% versus 23%). CONCLUSION: A diagnosis of PMR does not appear to increase the risk of premature death. Minor variations in causes of death were observed, but overall this study is reassuring for patients with PMR and for clinicians.

Comorbidities in patients with polymyalgia rheumatica prior to and following diagnosis: A case control and cohort study.

OBJECTIVES: To determine the burden of comorbidities, including glucocorticoid (GC) related adverse effects, in patients with polymyalgia rheumatica (PMR) before and after diagnosis. METHODS: We extracted anonymised electronic medical records of patients over the age of 40 years from the Clinical Practice Research Datalink from 1990-2016. Patients with PMR were individually matched on age, sex and registered General Practice to between three and five controls. The prevalence, cumulative probability and likelihood of a range of comorbidities was estimated. Odds ratios (ORs) and hazard ratios (HRs) were calculated using conditional logistic regression and Cox proportional hazards regression respectively, adjusted for a wide range of covariates. RESULTS: 31,984 patients with PMR were matched to 149,436 controls. PMR was prospectively associated with vascular disease (adjusted HR 1.23 [95% confidence interval (CI) 1.19, 1.28]), as well as respiratory (HR 1.25 [1.18, 1.32]), renal (HR 1.34 [1.30, 1.39]), and autoimmune diseases (HR 4.68 [4.35, 5.03]). Conversely, before PMR diagnosis, the risk of cancer (adjusted OR [OR] 0.89 [0.86, 0.93]) and neurological disease (OR 0.36 [0.33, 0.40]) was significantly lower. Patients with PMR had an increased risk of comorbidities associated with glucocorticoid (GC) use. CONCLUSIONS: Patients with PMR have a high comorbidity burden, both before and after diagnosis. Whilst further work is needed to more fully understand these associations, clinicians should be aware of the high prevalence of comorbid conditions in this group and the impact that treatment with glucocorticoids may have on comorbidity.

Comorbidities in polymyalgia rheumatica: a systematic review.

BACKGROUND AND AIM: Comorbidities are known to exist in many rheumatological conditions. Polymyalgia rheumatica (PMR) is a common inflammatory rheumatological condition affecting older people which, prior to effective treatment, causes severe disability. Our understanding of associated comorbidities in PMR is based only on case reports or series and small cohort studies. The objective of this study is to review systematically the existing literature on the comorbidities associated with PMR. METHODS: MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched for original observational research from inception to November 2016. Papers containing the words 'Polymyalgia Rheumatica' OR 'Giant Cell Arteritis' OR the terms 'PMR' OR 'GCA' were included. Article titles were reviewed based on pre-defined criteria by two reviewers. Following selection for inclusion, studies were quality assessed using the Newcastle-Ottawa tool and data were extracted. RESULTS: A total of 17,329 papers were reviewed and 41 were incorporated in this review, including three published after the search took place. Wide variations were found in study design, comorbidities reported and populations studied. Positive associations were found between PMR diagnosis and stroke, cardiovascular disease, peripheral arterial disease, diverticular disease and hypothyroidism. Two studies reported a positive association between PMR and overall malignancy rate. Seven studies reported an association between PMR and specific types of cancer, such as leukaemia, lymphoma, myeloproliferative disease and specified solid tumours, although nine studies found either no or negative association between cancer and PMR. CONCLUSION: Quantification of the prevalence of comorbidities in PMR is important to accurately plan service provision and enable identification of cases of PMR which may be more difficult to treat. This review highlights that research into comorbidities in PMR is, overall, methodologically inadequate and does not comprehensively cover all comorbidities. Future studies should consider a range of comorbidities in patients with a validated diagnosis of PMR in representative populations.

Incidence, prevalence and treatment burden of polymyalgia rheumatica in the UK over two decades: a population-based study.

OBJECTIVE: Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease in older people. Contemporary estimates of the incidence and prevalence are lacking, and no previous study has assessed treatment patterns at a population level. This study aims to address this. METHODS: We extracted anonymised electronic medical records of patients over the age of 40 years from the Clinical Practice Research Datalink in the period 1990-2016. The absolute rate of PMR per 100 000 person-years was calculated and stratified by age, gender and calendar year. Incidence rate ratios were calculated using a Poisson regression model. Among persons with PMR, continuous and total duration of treatment with glucocorticoids (GC) were assessed. RESULTS: 5 364 005 patients were included who contributed 44 million person-years of follow-up. 42 125 people had an incident diagnosis of PMR during the period. The overall incidence rate of PMR was 95.9 per 100 000 (95% CI 94.9 to 96.8). The incidence of PMR was highest in women, older age groups and those living in the South of England. Incidence appears stable over time. The prevalence of PMR in 2015 was 0.85 %. The median (IQR) continuous GC treatment duration was 15.8 (7.9-31.2) months. However, around 25% of patients received more than 4 years in total of GC therapy. CONCLUSIONS: The incidence rates of PMR have stabilised. This is the first population-based study to confirm that a significant number of patients with PMR receive prolonged treatment with GC, which can carry significant risks. The early identification of these patients should be a priority in future research.