Introduction
The results of recently completed cardiovascular outcomes trials in patients with type 2 diabetes mellitus (T2DM) suggest that sodium-glucose cotransporter-2 (SGLT2) inhibitors and ...glucagon-like peptide (GLP) 1 receptor agonists have enhanced cardioprotective properties in patients with established cardiovascular disease (eCVD), but to a lesser degree in those without eCVD. SGLT2 inhibitors appear to be particularly beneficial in patients with heart failure. As recent data for the UK are lacking, we undertook to identify the percentage of T2DM patients with eCVD and heart failure in the UK.
Methods
This was a retrospective cohort study that utilized the Clinical Practice Research Datalink (CPRD) database in the UK. We included de-identified adult patients with T2DM with at least one encounter in the CPRD database between 1 January 2018 and 31 December 2018 in the analysis and extracted the full health records of these patients. eCVD was defined as myocardial infarction, stroke, unstable angina pectoris, coronary artery disease and peripheral artery disease. We further assessed the number of patients with heart failure.
Results
From the total of 148,803 patients with T2DM analyzed (53% were male; mean age was 65 years), 52,601 (35.4%) suffered from eCVD and 8650 (5.8%) suffered from heart failure (73.7% of patients with heart failure overlap with those with atherothrombotic eCVD). Glycated hemoglobin levels of < 7% were attained by 49.5% of patients (with eCVD, 49.7%; without eCVD, 49.3%) (
p
< 0.001).
Conclusion
Approximately one-third of patients with T2DM in the UK have concomitant CVD.
Funding
Merck Sharp & Dohme Corp., a subsidiary Merck & Co., Inc., Kenilworth, NJ, USA.
Abstract
Background
Pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD). While clinical guidelines recommend specific drug therapies for pulmonary ...arterial hypertension (PAH), these drug therapies are not recommended for PH due to lung disease.
Methods
This was a retrospective cohort study using the Optum® Clinformatics® Data Mart from January 2009–September 2019. An algorithm was designed to identify adults with ≥ 2 ICD-9-CM or ICD-10-CM diagnosis codes for PH and with ≥ 2 diagnosis codes for COPD. Sensitivity analyses were conducted among subgroups of patients with evidence of a right heart catheterization (RHC) or pulmonary function test (PFT). Patient characteristics, medications used, and durations of use of PAH and COPD medications were analyzed.
Results
A total of 25,975 patients met the study inclusion criteria. Their mean age was 73.5 (SD 10.0) years and 63.8% were female. Medications targeting PAH were prescribed to 643 (2.5%) patients, most frequently a phosphodiesterase-5 inhibitor (2.1%) or an endothelin receptor antagonist (0.75%). Medications for COPD were prescribed to 17,765 (68.4%) patients, most frequently an inhaled corticosteroid (57.4%) or short-acting beta agonist (50.4%). The median durations of use ranged from 4.9 to 12.8 months for PAH medications, and from 0.4 to 5.9 months for COPD medications. Of the subgroup of patients with RHC (N = 2325), 257 (11.1%) were prescribed a PAH medication and 1670 (71.8%) used a COPD medication. Of the subgroup with a PFT (N = 2995), 58 (1.9%) were prescribed a PAH medication and 2100 (70.1%) a COPD medication.
Conclusions
Patients with PH associated with COPD were identified in a US administrative claims database. Very few of these patients received any of the medications recommended for PAH, and only about two thirds received medications for COPD.
Heart failure (HF) is highly prevalent in the United States. Approximately one-third to one-half of HF cases are categorized as HF with reduced ejection fraction (HFrEF). Patients with HFrEF are at ...risk of worsening HF, have a high risk of adverse outcomes, and experience higher health care use and costs. Therefore, it is crucial to identify patients with HFrEF who are at high risk of subsequent events after HF hospitalization.
Machine learning (ML) has been used to predict HF-related outcomes. The objective of this study was to compare different ML prediction models and feature construction methods to predict 30-, 90-, and 365-day hospital readmissions and worsening HF events (WHFEs).
We used the Veradigm PINNACLE outpatient registry linked to Symphony Health's Integrated Dataverse data from July 1, 2013, to September 30, 2017. Adults with a confirmed diagnosis of HFrEF and HF-related hospitalization were included. WHFEs were defined as HF-related hospitalizations or outpatient intravenous diuretic use within 1 year of the first HF hospitalization. We used different approaches to construct ML features from clinical codes, including frequencies of clinical classification software (CCS) categories, Bidirectional Encoder Representations From Transformers (BERT) trained with CCS sequences (BERT + CCS), BERT trained on raw clinical codes (BERT + raw), and prespecified features based on clinical knowledge. A multilayer perceptron neural network, extreme gradient boosting (XGBoost), random forest, and logistic regression prediction models were applied and compared.
A total of 30,687 adult patients with HFrEF were included in the analysis; 11.41% (3184/27,917) of adults experienced a hospital readmission within 30 days of their first HF hospitalization, and nearly half (9231/21,562, 42.81%) of the patients experienced at least 1 WHFE within 1 year after HF hospitalization. The prediction models and feature combinations with the best area under the receiver operating characteristic curve (AUC) for each outcome were XGBoost with CCS frequency (AUC=0.595) for 30-day readmission, random forest with CCS frequency (AUC=0.630) for 90-day readmission, XGBoost with CCS frequency (AUC=0.649) for 365-day readmission, and XGBoost with CCS frequency (AUC=0.640) for WHFEs. Our ML models could discriminate between readmission and WHFE among patients with HFrEF. Our model performance was mediocre, especially for the 30-day readmission events, most likely owing to limitations of the data, including an imbalance between positive and negative cases and high missing rates of many clinical variables and outcome definitions.
We predicted readmissions and WHFEs after HF hospitalizations in patients with HFrEF. Features identified by data-driven approaches may be comparable with those identified by clinical domain knowledge. Future work may be warranted to validate and improve the models using more longitudinal electronic health records that are complete, are comprehensive, and have a longer follow-up time.
Aims
In patients with heart failure (HF), we aimed to assess (i) the time trends in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) testing; (ii) patient characteristics associated with ...NT‐proBNP testing; (iii) distribution of NT‐proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT‐proBNP levels over time.
Methods and results
NT‐proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT‐proBNP levels before (in the previous 6 ± 3 months) and after (in the following 6 ± 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and ≥3000 ng/L at the second measurement = increased; (iii) ≥3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) ≥3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT‐proBNP testing and (ii) changes in NT‐proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT‐proBNP testing increased over time, up to 55% in 2018, and was almost two‐fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection fraction. Median NT‐proBNP was 3070 ng/L (Q1–Q3: 1220–7395), approximately three‐fold higher in WHFE vs. NWHFE. Compared with stable low NT‐proBNP levels, increased (OR 4.27, 95% CI 2.47–7.37) and stable high levels (OR 2.48, 95% CI 1.58–3.88) were independently associated with a higher risk of WHFE. Results were consistent in the HFrEF population.
Conclusions
NT‐proBNP testing increased over time but still was only performed in half of the patients. Testing was associated with a WHFE, with features of more severe HF and for differential diagnosis purposes. Increased and stable high levels were associated with a WHFE. Overall, our data highlight the potential benefits of carrying further implementation of NT‐proBNP testing in clinical practice.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Introduction
Current guidelines recommend adding an oral antihyperglycemic agent (AHA) to metformin in patients with type 2 diabetes mellitus (T2DM) uncontrolled on metformin. Recent randomized ...clinical trials (RCTs) have demonstrated that adding dual AHAs instead of a single AHA provided more effective glycemic control. However, the comparative efficacy of approved single and dual initiation strategies is unknown. Therefore, we conducted a Bayesian network meta-analysis to compare the efficacy of dual and single add-on oral AHAs in patients uncontrolled on metformin.
Methods
A systematic literature review of RCTs was conducted following Cochrane and ISPOR guidelines. MEDLINE, Embase, and CENTRAL were searched from inception to November 19, 2019. Approved oral doses of sodium–glucose co-transporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists in single or dual initiation therapies were indirectly compared. Outcomes focused on efficacy and included mean change from baseline in hemoglobin A1c (HbA1c), weight, systolic blood pressure (SBP), diastolic blood pressure, and achieving HbA1c target < 7% at 24–26 weeks. Fixed and random effects models with Markov chain Monte Carlo simulations were used.
Results
Of 1955 unique records screened, 25 RCTs (14,264 participants) were included. In patients uncontrolled on metformin, dual AHA added to metformin had statistically significant or a trend of greater reduction in HbA1c compared to single AHAs, with ertugliflozin + sitagliptin showing the greatest improvement. Statistically significant reductions in weight and SBP were observed with ertugliflozin + sitagliptin, ertugliflozin, or canagliflozin compared to single initiation DPP-4 inhibitors.
Conclusion
For reduction of HbA1c, weight, and SBP in patients uncontrolled on metformin, add-on dual AHAs showed greater improvement compared to single AHAs. These findings can further inform the treatment of T2DM patients uncontrolled on metformin.
This retrospective study was conducted to evaluate all‐cause healthcare resource utilization (HCRU) and costs in commercially insured patients living with pulmonary arterial hypertension (PAH) and ...explore end‐of‐life (EOL)‐related HCRU and costs. Data from the IQVIA PharMetrics® Plus database (October 2014 to May 2020) were analyzed to identify adults (≥18 years) with PAH (PAH cohort) and those without PH (non‐PH cohort). Patients were required to have data for ≥12 months before (baseline) and ≥6 months after (follow‐up) the first observed PH diagnosis (index date) for PAH cohort or pseudo index date for non‐PH cohort. A PAH EOL cohort was similarly constructed using a broader data window (October 2014 to March 2022) and ≥1 month of follow‐up. Annualized all‐cause HCRU and costs during follow‐up were compared between PAH and non‐PH cohorts after 1:1 matching on propensity scores derived from patient characteristics. EOL‐related HCRU and costs were explored within 30 days and 6 months before the death date and estimated by a claims‐based algorithm in PAH EOL cohort. The annual all‐cause total ($183,616 vs. $20,212) and pharmacy ($115,926 vs. $7862; both p < 0.001) costs were 8 and 14 times higher, respectively, in the PAH cohort versus matched non‐PH cohort (N = 386 for each). In PAH EOL cohort (N = 28), the mean EOL‐related costs were $48,846 and $167,524 per patient within 30 days and 6 months before the estimated death, respectively. Hospitalizations contributed 58.8%–70.8% of the EOL‐related costs. The study findings indicate substantial HCRU and costs for PAH. While pharmacy costs were one of the major sources, hospitalization was the primary driver for EOL‐related costs.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Based on available data from randomized clinical trials, patients with heart failure with reduced ejection fraction (HFrEF) and worsening HF events (WHFE) have substantial disease burden and poor ...outcomes. WHFE clinical outcome data in non-clinical trial patients, more representative of the US clinical practice, has not been demonstrated.
CHART-HF collected data from two complementary, non-clinical trial cohort with HFrEF (LVEF <45 %): 1) 1,000 patients from an integrated delivery network and 2) 458 patients from a nationwide physician panel. CHART-HF included patients with WHFE between 2017 and 2019 followed by an index outpatient cardiology visit ≤6 months, and patients without WHFE in a given year between 2017 and 2019, with the last outpatient cardiology visit in the same year as the index visit. Compared to patients without WHFE (after covariate adjustment, all p < 0.05), patients with WHFE had a greater risk of HF-related hospitalization (hazard ratio HR: 1.53–2.40) and next WHFE event (HR: 1.67–2.41) following index visits in both cohorts.
HFrEF patients with recent WHFE consistently had worse clinical outcomes in these non-clinical trial cohorts. Despite advances in therapies, unmet need to improve clinical outcomes in HFrEF patients with WHFE remains.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims
The N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is a commonly used biomarker in heart failure for diagnosis and prognostication. We aimed to determine the prevalence of NT‐proBNP ...testing, distribution of NT‐proBNP concentrations, and factors associated with receiving an NT‐proBNP test in patients with heart failure with reduced ejection fraction (HFrEF), including the subset with a worsening heart failure event (WHFE).
Methods and results
This was a retrospective cohort study using two US databases: (i) the de‐identified Humana Research Database between January 2015 and December 2018 and (ii) the Veradigm PINNACLE Registry® between July 2013 and September 2017. We included adult patients with a confirmed diagnosis of HFrEF. In each data source, a subgroup of patients with a WHFE was identified, where a WHFE was defined as a heart failure‐related hospitalization or receipt of intravenous diuretics. Bivariate and multivariate analyses were conducted to assess factors associated with receiving NT‐proBNP testing. In Cohort 1 (n = 249 238), 9.2% of patients with HFrEF and 10.8% of patients with a WHFE received NT‐proBNP testing. When restricted to patients with at least one laboratory claim, 11.3% of patients with HFrEF and 13.2% of those with a WHFE received NT‐proBNP testing. In Cohort 2 (n = 91 444), 2.3% of patients with HFrEF were tested. Median (inter‐quartile range) NT‐proBNP concentrations among patients with HFrEF were 1399 (423–4087) pg/mL in Cohort 1 and 394 (142–688) pg/mL in Cohort 2. Median (inter‐quartile range) NT‐proBNP concentrations in the subset of patients with a WHFE in each cohort were 2209 (740–5894) and 464 (174–783) pg/mL, respectively. In Cohort 1, 13.4% of all HFrEF patients receiving NT‐proBNP testing and 18.9% of patients with a WHFE had NT‐proBNP values >8000 pg/mL; in Cohort 2, these percentages were 1.0% and 2.5%, respectively.
Conclusions
In US clinical practice, NT‐proBNP testing was not frequently performed in patients with HFrEF. NT‐proBNP concentrations varied across data sources and subpopulations within HFrEF.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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