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.

Interstitial lung disease is a risk factor for ischaemic heart disease and myocardial infarction.

OBJECTIVES: Despite many shared risk factors and pathophysiological pathways, the risk of ischaemic heart disease (IHD) and myocardial infarction (MI) in interstitial lung disease (ILD) remains poorly understood. This lack of data could be preventing patients who may benefit from screening for these cardiovascular diseases from receiving it. METHODS: A population-based cohort study used electronic patient records from the Clinical Practice Research Datalink and linked Hospital Episode Statistics to identify 68 572 patients (11 688 ILD exposed (mean follow-up: 3.8 years); 56 884 unexposed controls (mean follow-up: 4.0 years), with 349 067 person-years of follow-up. ILD-exposed patients (pulmonary sarcoidosis (PS) or idiopathic pulmonary fibrosis (PF)) were matched (by age, sex, registered general practice and available follow-up time) to patients without ILD or IHD/MI. Rates of incident MI and IHD were estimated. HRs were modelled using multivariable Cox proportional hazards regression accounting for potential confounders. RESULTS: ILD was independently associated with IHD (HR 1.85, 95% CI 1.56 to 2.18) and MI (HR 1.74, 95% CI 1.44 to 2.11). In all disease categories, risk of both IHD and MI peaked between ages 60 and 69 years, except for the risk of MI in PS which was greatest <50 years. Men with PF were at greatest risk of IHD, while women with PF were at greatest risk of MI. CONCLUSIONS: ILD, particularly PF, is independently associated with MI and IHD after adjustment for established cardiovascular risk factors. Our results suggest clinicians should prioritise targeted assessment of cardiovascular risk in patients with ILD, particularly those aged 60-69 years. Further research is needed to understand the impact of such an approach to risk management.