Introduction: Acute COPD exacerbations (AECOPD) are associated with transient cardiovascular risk, attributed to systemic inflammatory effects. Whether cardiovascular risk escalates within the same individual across successive exacerbations has not been characterised previously in the international EXACOS-CV programme. New Zealand is the first to assess a within-person dose-response pattern, which may suggest cumulative vascular injury and carry implications for cardiovascular monitoring in recurrent disease.

Aims: To determine whether the magnitude and duration of post-AECOPD cardiovascular risk increase with each successive exacerbation. To characterise the within-person dose-response gradient across first, second, and third-or-later exacerbations.

Methods: Incident COPD cohort (56,830 patients; prevalent COPD excluded) from linked New Zealand national administrative health data (2014–2019). Separate time-dependent Cox models were fitted for each exacerbation rank (first, second, third-or-later) using the patient's own unexposed person-time as reference. The composite outcome was MACE or all-cause death, adjusted for age, sex, comorbidities, ethnicity, and deprivation quintile.

Results: Among 56,830 incident COPD patients (138,479 person-years; 21,133 composite events), the 1–7 day HR after the 1, 2 and 3+ exacerbations was 2.66 (95% CI 2.33–3.03), 3.38 (2.96–3.87), and 3.49 (2.93–4.16), respectively (all p < 0.001). The 8–14 day HR showed the same gradient: 1.22, 1.97, and 2.19 for ranks 1, 2, and 3+. After a first exacerbation, the elevated risk normalised by 90 days; after a second, it remained elevated to 31–90 days (HR 1.34, 95% CI 1.23–1.46). The 31–90-day HR also increased to 1.23, 1.34, and 1.39 for ranks 1, 2, and 3+, respectively. Rank 2 and 3+ patients had already survived at least one prior exacerbation; the observed gradient is therefore likely conservative.

Conclusions: Post-AECOPD cardiovascular risk increases with each successive exacerbation, in both magnitude and duration. Cumulative cardiovascular vulnerability supports a vascular injury hypothesis and suggests intensified post-exacerbation monitoring and intervention.

Keywords: Disease Exacerbation; Cardiovascular Diseases; COPD

Introduction: Māori and Pacific peoples in New Zealand have disproportionate rates of COPD and cardiovascular disease; acute COPD exacerbations (AECOPD) further elevate cardiovascular risk. The international EXACOS-CV programme has quantified this association across eight countries without ethnic stratification; New Zealand is the first to include health equity analysis by ethnicity and socioeconomic deprivation. Whether these inequities are independent has not been examined.

Aims: To quantify ethnic and socioeconomic disparities in AECOPD frequency and MACE/death rates. To examine whether these disparities are independent structural effects.

Methods: Population-based retrospective cohort using linked national administrative health data (2014–2019); adults with COPD identified from hospitalisation and dispensing records. Negative binomial regression estimated IRRs for AECOPD frequency and MACE/death with progressive adjustment for age, sex, comorbidities, ethnicity, and deprivation quintile. Time-dependent Cox regression examined the AECOPD→MACE/death hazard by ethnicity.

Results: Among 58,037 patients with COPD (142,168 person-years; Māori 20.4%), 21,972 experienced a composite MACE/death event. Age-sex standardised MACE/death rates were 144.6 vs 99.5 per 1,000 person-years (Māori vs European); a 20% disparity remained after comorbidity adjustment (IRR 1.20, 95% CI 1.15–1.25). Māori patients had 29% more exacerbations per year (IRR 1.29, 95% CI 1.25–1.32). The most deprived quintile had 34% higher MACE/death rates than the least deprived (IRR 1.34, 95% CI 1.27–1.41). Ethnicity and deprivation were independent structural determinants; the deprivation gradient was consistent across ethnic groups (LRT p < 0.001). Cox interaction showed ethnic MACE/death disparities arise from higher background cardiovascular hazard in Māori and Pacific patients (p = 0.0014). Pacific patients showed a divergent risk profile warranting further investigation.

Conclusions: Ethnic and socioeconomic inequities in COPD outcomes persist after full comorbidity adjustment as independent structural determinants, each requiring separate policy responses. Future work should examine mechanisms driving these disparities, including post-exacerbation cardiovascular and respiratory care.

Keywords: Healthcare Disparities, Cardiovascular Diseases, COPD

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) may exert antifibrotic effects in the lung. However, the extent to which these properties confer clinically meaningful benefit on idiopathic pulmonary fibrosis (IPF) remains uncertain.
Aims: To assess the risk of IPF with the use of SGLT2i in patients with type 2 diabetes (T2D).
Methods: We conducted a population-based cohort study using a nationwide healthcare database of Korea (2002–2023). Patients with T2D who initiated SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) were included, and followed from the date of study drug initiation until the earliest occurrence of IPF, discontinuation or switching of the index drug class, death, or Dec 31, 2023. Hazard ratios (HRs) and rate differences (RDs) per 100,000 person-years were estimated after normalized inverse probability treatment weighting. In additional analyses, we assessed risks of all-cause and respiratory-related mortality among patients with pre-existing IPF.
Results: We identified 548,411 SGLT2i users (mean age, 55.6 years; 59.4% male) and 3,177,716 DPP4i users (mean age, 61.2 years; 58.3% male). During a median follow-up of 1.16 years, weighted incidence rates of IPF were 20.53 and 31.74 per 100,000 person-years in SGLT2i and DPP4i users, respectively. Compared with DPP4i, SGLT2i was associated with a lower risk of IPF (HR 0.62; 95% CI, 0.53 to 0.72; RD -11.10, 95% CI, -13.30 to -8.91). Among patients with pre-existing IPF, SGLT2i was also associated with lower risks of all-cause and respiratory-related mortality, with HRs of 0.72 (95% CI) and 0.50 (95% CI), respectively.
Discussion: In this nationwide cohort study, SGLT2i was associated with a lower risk of IPF compared with DPP4i in patients with T2D, and lower risks of all-cause and respiratory-related mortality in patients with pre-existing IPF. These findings suggest a potential protective effect of SGLT2I against IPF and warrant further evaluation in clinical trials.

Introduction: Intravenous immunoglobulin (IVIg) therapy has been associated with thromboembolic events (TEEs), but prior studies are limited by confounding by indication and heterogeneous designs. The timing and magnitude of any short-term thromboembolic risk remain incompletely characterized.

Aims: To evaluate the short-term risk of TEEs following IVIg administration and determine whether risk is concentrated in early post-infusion periods.

Methods: We conducted a new-user comparative cohort study with a secondary self-controlled risk interval analysis using linked hospital administrative data from 2013 to 2020. Adults receiving IVIg were compared with time-aligned hospitalized patients without IVIg exposure using inverse probability weighting targeting the treated population. TEEs included venous and arterial events identified from diagnosis codes within 30 and 90 days. Self-controlled analyses compared post-exposure risk windows with a later within-person control window.

Results: The analytic cohort included 2,855 IVIg recipients and 713,727 time-aligned comparators. The weighted 30-day risk of TEE was 1.61% among IVIg recipients versus 0.41% among comparators, an absolute risk difference of 1.20%. The adjusted 90-day hazard ratio was 1.69 (95% CI, 1.35 to 2.13). Risk was higher during days 0 to 30 (HR, 1.94; 95% CI, 1.37 to 2.74) than days 31 to 90 (HR, 1.57; 95% CI, 1.16 to 2.11). In self-controlled analyses, incidence rate ratios were highest during days 0 to 2 after IVIg administration (7.16; 95% CI, 3.24 to 15.82), with lower estimates thereafter.

Conclusions: IVIg administration was associated with a higher short-term incidence and risk of TEEs, particularly shortly after exposure. Findings support careful thrombotic risk assessment and close monitoring in the early post-infusion period, although residual confounding and time-varying factors cannot be excluded.

Keywords: intravenous immunoglobulin; thromboembolism; pharmacoepidemiology

Introduction: Venous thromboembolism (VTE) is a clinically important event associated with poor prognosis in patients with locally advanced (LA) or metastatic (m) non-small cell lung cancer (NSCLC) initiating systemic therapy in Japan. However, the incidence of severe VTE and its year-to-year trends remain poorly characterized in this population, with limited published evidence despite substantial changes in treatment patterns.

Aims: This study aims to estimate the incidence of VTE within one year after initiation of systemic therapy.

Methods: This retrospective cohort study used the Medical Data Vision (MDV) claims database from 2015 to 2024. Patients aged ≥18 years initiating systemic therapy for LA/mNSCLC were included, excluding those with lung cancer surgery within 180 days before the index date. The index date was treatment initiation, and patients were followed up to 1 year. VTE was defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), with severe VTE defined by inpatient diagnosis and imaging during hospitalization.

Results: A total of 99,505 patients were included; median age 72 years and 66.5% males. Of these, 733 patients experienced severe VTE. The severe VTE incidence rate per 100 person-years was 1.40 (95% CI: 1.30-1.51), with DVT and PE incidence of 0.95 (95% CI: 0.87-1.04) and 0.45 (95% CI: 0.39-0.51), respectively. Yearly VTE incidence ranged from 1.23 (95% CI: 0.90-1.63) in 2016 to 1.77 (95% CI: 1.43-2.17) in 2021, with values of 1.44 (95% CI: 1.04-1.94) in the first year (2015) and 1.24 (95% CI: 1.00-1.53) in the final year (2024).

Conclusions: This study characterized the incidence rate and year-to-year trends of severe VTE in patients with LA/mNSCLC initiating systemic therapy. These findings can support understanding of the epidemiology and the background incidence of severe VTE in this population.

Keywords: Venous thromboembolism, non-small cell lung cancer, Real World Evidence

Background: Older patients with pulmonary embolism (PE) are at increased risk of bleeding, which is associated with adverse outcomes, making early risk assessment particularly important. This study evaluated the short-term performance of commonly used bleeding risk scores in patients aged ≥65 years.

Methods: An analysis was conducted in a multicentre, prospective study of patients aged ≥65 years with PE receiving anticoagulation (NCT02943343, 2016). The performance of the PE-SARD, Kuijer, RIETE, BACS, and ATRIA scores was evaluated using the time-dependent area under the curve (AUC) analysis. Calibration was assessed with calibration plots. Sensitivity, specificity, and positive predictive values were calculated. The primary outcomes were major bleeding (MB) at 7 and 14 days.

Results: Among 3,661 anticoagulated patients aged ≥65 years with acute PE, MB occurred in 18 (0.5%) and 36 (1.0%) patients at 7 and 14 days, respectively, and clinically relevant non-major bleeding (CRNMB) in 69 (1.9%) and 105 (2.9%) patients. Patients with bleeding events had higher mortality than those without bleeding. Discrimination for short-term MB was low to moderate across scores, with RIETE (AUC 0.76, 95% CI 0.65-0.87) and PE-SARD (AUC 0.74, 95% CI 0.63-0.85) showing the most consistent performance at 7 days. Overall discrimination declined at 14 days. All scores demonstrated limited ability to predict CRNMB, and no model showed a consistent net clinical benefit.

Conclusions: In older patients with PE, bleeding risk scores showed low-to-moderate discrimination for short-term bleeding, with moderate early performance observed only in selected scores. None of the scores reliably identified CRNMB, highlighting the limitations of baseline risk assessment in acute care settings.