Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. ...Understanding GDMT use is critical to improving clinical practice.
This study sought to describe GDMT use in Japan, Sweden, and the United States in contemporary real-world settings.
EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational cohort study using routine-care databases. Patients initiating any GDMT within 12 months of a hospitalization for heart failure (hHF) discharge were included. Dapagliflozin (the only sodium-glucose cotransporter-2 inhibitor approved at study onset), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Doses and discontinuation were assessed in the 12 months following initiation. Target dose was defined as ≥100% of the guideline-recommended dose.
Overall, 266,589 patients were included. Mean times from hHF to GDMT initiation were longer for novel GDMTs (dapagliflozin or sacubitril/valsartan) than for other GDMTs: 39 and 44 vs 12 to 13 days (Japan), 44 and 33 vs 22 to 31 days (Sweden), and 33 and 19 vs 18 to 24 days (United States). Pooled across countries, proportions of patients who discontinued therapy (not including switches from ACE inhibitor or ARB to sacubitril/valsartan) within 12 months were 23.5% (dapagliflozin), 26.4% (sacubitril/valsartan), 38.4% (ACE inhibitors), 33.4% (ARBs), 25.2% (beta-blockers), and 42.2% (MRAs). Corresponding target dose achievements were 75.7%, 28.2%, 20.1%, 6.7%, 7.2%, and 5.1%, respectively.
Initiation of novel GDMTs is delayed compared with other GDMTs. Few patients received target doses of GDMTs requiring uptitration. Persistence was higher for dapagliflozin than other GDMTs.
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Elevated levels of blood leukocytes have been associated with acute coronary events (CEs), but data on leukocyte subclasses are limited. This study aimed to explore whether blood lymphocyte and ...neutrophil counts are associated with incidence of CEs and with fatal outcome in subjects who subsequently experienced a first CE.
Neutrophil and lymphocyte counts were measured in 27 419 subjects from the general population without a history of CEs, heart failure, or atrial fibrillation. Incidence of CEs was studied in relation to leukocyte counts during a mean follow-up of 13.6 years. Neutrophil but not lymphocyte counts were significantly associated with incidence of CEs. After adjustments for confounding factors, the hazard ratios (95% confidence interval) were 1.00 (reference), 1.07 (0.94-1.23), 1.09 (0.95-1.25), and 1.39 (1.22-1.59) for subjects with neutrophils in the first, second, third, and fourth (highest) sex-specific quartiles, respectively (P for trend <0.001). Of the 1965 subject who had a CE, 471 subjects died on the first day of the CE, in- or outside hospital. The proportions of subjects who died the first day were 19%, 21%, 25%, and 28%, respectively in the first, second, third, and fourth quartiles (P for trend <0.001).
Increased neutrophil counts are associated with incidence of CEs and increased case-fatality rate after a CE.
Key Points Newly detected, moderately progressed CKD is associated with high clinical risks and health care costs. Most patients with moderately progressed CKD do not have diabetes and are at the ...same clinical risk as those with diabetes. Substantial inertia with kidney-protective treatment is observed when moderately progressed CKD is detected. Background Kidney-protective treatments (renin–angiotensin system inhibitors and sodium–glucose cotransporter-2 inhibitors SGLT-2is) can delay CKD progression, cardiovascular events, and death. Methods This observational cohort study used electronic health records and claims data from Japan, Sweden, and the United States to assess 1-year mortality/hospitalization event rates per 100 patient-years (PYs), cumulative hospital health care costs per patient, and kidney-protective treatment use before/after SGLT-2i (dapagliflozin) approval for CKD (2021) for patients with CKD stage 3–4 with/without type 2 diabetes (T2D). Results Among 449,232 patients (across-country median age range 74–81 years), 79% did not have T2D. Prevalence ranges for atherosclerotic cardiovascular disease and heart failure were 20%–36% and 17%–31%, respectively. Baseline kidney-protective treatment (renin–angiotensin system inhibitor and/or SGLT-2i) use was limited, especially among patients without T2D. Event rates were high for CKD (11.4–44.4/100 PYs) and heart failure (7.4–22.3/100 PYs). Up to 14.6% of patients had died within 1 year. Hospital costs were higher for CKD and heart failure than for atherosclerotic cardiovascular disease. After incident CKD, kidney-protective treatment initiation was low (8%–20%) and discontinuation was high (16%–27%), especially among patients without T2D. Conclusions Incident CKD was associated with substantial morbidity, mortality, costs, and undertreatment, especially in patients without T2D, who represented the majority of patients. This highlights an urgent need for early CKD detection and better kidney-protective treatment use in moderate CKD.
Aims
Exposure to corticosteroids is known to increase the risk of developing type 2 diabetes. We estimated the risk of incident type 2 diabetes in selected patient groups exposed to systemic ...corticosteroids.
Materials and methods
In a retrospective, observational cohort study, using real‐world data from UK primary care, patients were selected who had at least one episode of exposure to oral or intravenous corticosteroids for any indication. Corticosteroid‐exposed patients were matched with non‐exposed patients. Relative dosage was estimated as a weight‐based, prednisolone‐equivalent dose. Crude rates of progression to type 2 diabetes were determined for patient groups defined by relevant steroid‐related and phenotypic characteristics present at corticosteroid exposure.
Results
Overall, rates of incidence of type 2 diabetes were 12.5 and 6.7 events per thousand person‐years' (pkpy) exposure, respectively, in those who received at least one dose of corticosteroids versus those never exposed. This represented a rate ratio of 1.85 (95% CI 1.74‐1.97). The incidence of type 2 diabetes was found to be associated with several of the selected characteristics, both individually and multi‐dimensionally. The highest rate of incident type 2 diabetes was observed in very severely obese men aged 46‐55 years having had the longest corticosteroid exposure and highest corticosteroid dose (190 incident events pkpy exposure).
Conclusions
Corticosteroid exposure increased the risk of incident type 2 diabetes, and there was evidence of both a dose‐response and a duration response. The impact of corticosteroid exposure upon the rate of incident type 2 diabetes appeared, however, to involve a complex, multi‐dimensional interaction between the selected characteristics, some of which might be impacted by reverse causality.
Low-grade inflammation has been repeatedly associated with cardiovascular diseases but the relationship with incidence of atrial fibrillation (AF) remains unclear. We explored the association between ...elevated plasma levels of inflammation-sensitive proteins (ISPs) and incidence of AF in a population-based cohort. Plasma levels of five ISPs (fibrinogen, haptoglobin, ceruloplasmin, α₁- antitrypsin and orosomucoid) and two complement factors (C3 and C4) were measured in 6,031 men (mean age 46.8 years) without history of myocardial infarction, heart failure, stroke or cancer. Incidence of hospitalizations due to AF during a mean follow-up of 25 years was studied both in relation to individual inflammatory proteins and the number of elevated ISPs. During follow-up, 667 patients were hospitalized with a diagnosis of AF. After adjustment for potential confounding factors, the hazard ratios (HR) for AF were 1.00 (reference), 1.08 (95% CI: 0.88-1.31), 1.07 (CI: 0.84-1.36), and 1.40 (CI: 1.12-1.74), respectively, in men with none, one, two and three or more ISPs in the 4th quartile (P for trend = 0.007). Ceruloplasmin was the only individual ISP significantly associated with incidence of AF after adjustment for confounding factors (HR 1.17 per standard deviation, 95% CI: 1.08-1.26). In conclusion, a score of five ISPs was associated with long-term incidence of hospitalizations due to AF in middle-aged men. Of the individual ISPs, a significant association was observed for ceruloplasmin, a protein previously associated with copper metabolism and oxidative stress.
ObjectivesThe protective effect of lipid-lowering treatment for secondary prevention after coronary heart disease (CHD) has been well documented. Current guidelines recommend a target level for ...low-density lipoprotein cholesterol (LDL-C) of ≤1.8 mmol/L. The aim was to describe lipid-lowering treatment patterns and to provide an estimate of the potential reductions in cardiovascular disease (CVD) events with improved adherence to guidelines.DesignCross-sectional.SettingPrimary care in a large Swedish region.Participants37 120 patients with CHD in a Swedish regional primary care quality register (QregPV), by 31 December 2015.Primary and secondary outcome measuresProportion of patients on statin treatment and proportion of patients achieving LDL-C ≤1.8 mmol/L. Estimated number of CVD events calculated for (1) current treatment, (2) improved treatment and (3) lowered LDL-C, based on applying rate reductions from meta-analyses of randomised trials to the potentially undertreated population. Risk estimation modelling was based on 52 042 patients in the same register on January 2011 followed for 5 years.ResultsOf 37 120 patients, 18% reached LDL-C ≤1.8 mmol/L and 32% were not on statin treatment. Based on individual risks, the estimated number of CVD events in the study group over 5 years was 9209/37 120. If all patients without a statin or with less potent statin treatment were given atorvastatin 80 mg, an estimated reduction of CVD events by 14% (7901 vs 9209) was seen. If all patients achieved LDL-C ≤1.8 mmol/L, the number of events was estimated to be reduced by 18% (7577 vs 9209).ConclusionOne-third of patients with CHD in primary care were not on lipid-lowering treatment. Based on the assumption that included patients would react to statin therapy the same way as the patients in randomised trials, improved adherence to treatment guidelines could lead to a substantial reduction in new CVD events.
Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. ...Understanding GDMT use is critical to improving clinical practice.
This study sought to describe GDMT use in Japan, Sweden, and the United States in contemporary real-world settings.
EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational cohort study using routine-care databases. Patients initiating any GDMT within 12 months of a hospitalization for heart failure (hHF) discharge were included. Dapagliflozin (the only sodium-glucose cotransporter-2 inhibitor approved at study onset), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Doses and discontinuation were assessed in the 12 months following initiation. Target dose was defined as ≥100% of the guideline-recommended dose.
Overall, 266,589 patients were included. Mean times from hHF to GDMT initiation were longer for novel GDMTs (dapagliflozin or sacubitril/valsartan) than for other GDMTs: 39 and 44 vs 12 to 13 days (Japan), 44 and 33 vs 22 to 31 days (Sweden), and 33 and 19 vs 18 to 24 days (United States). Pooled across countries, proportions of patients who discontinued therapy (not including switches from ACE inhibitor or ARB to sacubitril/valsartan) within 12 months were 23.5% (dapagliflozin), 26.4% (sacubitril/valsartan), 38.4% (ACE inhibitors), 33.4% (ARBs), 25.2% (beta-blockers), and 42.2% (MRAs). Corresponding target dose achievements were 75.7%, 28.2%, 20.1%, 6.7%, 7.2%, and 5.1%, respectively.
Initiation of novel GDMTs is delayed compared with other GDMTs. Few patients received target doses of GDMTs requiring uptitration. Persistence was higher for dapagliflozin than other GDMTs.
Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously ...developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts.
We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score.
During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04).
In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
Objectives
Red blood cell distribution width (RDW), a measure of variation in erythrocyte volume, has been associated with several cardiovascular disorders, but the relationship with atrial ...fibrillation (AF) remains unclear. We investigated the association between RDW and incidence of first hospitalization due to AF in a population‐based cohort.
Design
Red blood cell distribution width was measured in 27 124 subjects from the general population (age 45–73 years, 62% women) with no history of AF, heart failure, myocardial infarction or stroke. The association between baseline RDW and incidence of AF identified from the Swedish Hospital Discharge Register was evaluated.
Results
During a mean follow‐up of 13.6 years, 1894 subjects (53% men) were hospitalized with a diagnosis of AF. After adjustment for potential confounding factors, including cardiovascular disease risk factors, nutrient intake (iron, vitamin B12 and folate) and several haematological parameters (haemoglobin concentration, mean corpuscular volume and corpuscular haemoglobin content), the hazard ratio (HR) for incidence of AF was 1.33 95% confidence interval (CI) 1.16–1.53 for the fourth versus first quartile of RDW (P for trend <0.001). The results were essentially unchanged when subjects with incident myocardial infarction or hospitalizations because of heart failure were censored from the analysis (HR 1.30, 95% CI 1.13–1.51; P for trend = 0.001).
Conclusion
Red blood cell distribution width was associated with incidence of AF independently of several cardiovascular, nutritional and haematological factors in this study of middle‐aged subjects from the general population.
Aims
To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk ...factors associated with the incidence of such complications.
Methods
We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10‐year follow‐up period was studied in all individuals who had no complications at baseline.
Results
Among people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c, BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid‐lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow‐up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration.
Conclusions
People with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration.
What's new?
Previous studies in long‐term survivors of Type 1 diabetes have mainly been cross‐sectional, relying on self‐reported data, and the results have been inconsistent.
This register‐based study of 18 450 people with Type 1 diabetes shows that those who have survived ≥ 50 years without complications are significantly younger and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications.
HbA1c is a predictor of macrovascular disease, independently of diabetes duration, even after 50 years’ duration of Type 1 diabetes.
It is important to identify factors that may protect individuals with Type 1 diabetes from major complications.
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