Elevated lipoprotein(a) increases risk of subsequent major adverse cardiovascular events (MACE) and coronary revascularisation in incident ASCVD patients: a cohort study from the UK biobank

Background and aims: Elevated lipoprotein(a) [Lp(a)] is a genetic driver for atherosclerotic cardiovascular disease (ASCVD). We aimed to provide novel insights on the associated risk of elevated versus normal Lp(a) levels on major adverse cardiovascular events (MACE) in an incident ASCVD cohort. Methods: This was an observational cohort study of incident ASCVD patients. MACE counts and incidence rates (IRs) per 100-person-years were reported for patients with normal (<65 nmol/L) and elevated (>150 nmol/L) Lp(a) within the first year after incident ASCVD diagnosis and overall follow-up. Cox proportional hazard models quantified the risk of MACE associated with a 100 nmol/L increase in Lp(a). Results: The study cohort included 32,537 incident ASCVD patients; 5204 with elevated and 22,257 with normal Lp(a). Of those with elevated Lp(a), 41.2% had a subsequent MACE, versus 35.61% with normal Lp(a). Within the first year of follow-up, the IRs of composite MACE and coronary revascularisation were significantly higher (p < 0.001) in patients with elevated versus normal Lp(a) (IR difference 6.79 and 4.66). This trend was also observed in the overall follow-up (median 4.7 years). Using time to first subsequent MACE, a 100 nmol/L increase in Lp(a) was associated with an 8.0% increased risk of composite MACE, and 18.6% increased risk of coronary revascularisation during the overall follow-up period. Conclusions: The association of elevated Lp(a) with increased risk of subsequent MACE and coronary revascularisation, highlights a population who may benefit from earlier and more targeted intervention for cardiovascular risk including Lp(a), particularly within the first year after ASCVD diagnosis. Proactive Lp(a) testing as part of routine clinical practice can help to identify and better manage these higher-risk individuals

Real-world comparative effectiveness of ARNI versus ACEi/ARB in HF with reduced or mildly reduced ejection fraction

Aims Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) with a class-1 guideline recommendation. We assessed the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) on all-cause and cardiovascular (CV)-related mortality and hospitalizations in heart failure (HF) with reduced or mildly reduced ejection fraction (EF). Methods Patient-level clinical, laboratory, drug dispensation, hospitalization, and mortality data were derived from the Swedish Heart Failure Registry (SwedeHF) and interlinked databases (1 April 2016-31 December 2020). Eligible ARNI:ACEi/ARB patients (n = 7275:24,604) had a left ventricular EF &amp;lt; 50%. Mortality and hospitalizations with ARNI (&amp;lt;= 3 months pre-/post-1 April 2016 index [SwedeHF]; n = 1506) versus ACEi/ARB (&amp;lt;= 3 months post-index; n = 17,108) were assessed using propensity score matching (1:1 ratio) with clinical variables, and sensitivity analysis (1:2/1:3 with, and 1:2 without clinical variables). Results ARNI induced a 23% reduction in all-cause mortality versus ACEi/ARB (1:1 hazard ratio [HR; 95% confidence interval (CI)]: 0.77 [0.63-0.95], p = 0.013), and a non-significant 23% relative risk reduction in CV-related mortality (0.77 [0.54-1.09], p = 0.13), but no difference in all-cause or CV-related hospitalization (1.02 [0.91-1.13]; p = 0.76; 1.01 [0.91-1.15]; p = 0.84, respectively). Sensitivity analyses confirmed all-cause mortality was reduced for ARNI versus ACEi/ARB (HR 0.90 [95% CI 0.82-0.99], p = 0.026), but not CV-related mortality (HR 1.04 [95% CI 0.89-1.22], p = 0.63). Conclusions In this nationwide real-world study including a population of patients with HF with reduced or mildly reduced EF, ARNI as part of guideline-led Swedish clinical practice was associated with a statistically significant relative risk reduction in all-cause mortality compared with ACEi/ARB.Funding Agencies|University of Gothenburg - Novartis Sweden AB</p

Clinical characteristics and mortality of patients with heart failure in Southern Sweden from 2013 to 2019 : a population-based cohort study

OBJECTIVES: To describe clinical characteristics and prognosis related to heart failure (HF) phenotypes in a community-based population by applying a novel algorithm to obtain ejection fractions (EF) from electronic medical records. DESIGN: Retrospective population-based cohort study. SETTING: Data were collected for all patients with HF in Southwest Sweden. The region consists of three acute care hospitals, 40 inpatient wards, 2 emergency departments, 30 outpatient specialty clinics and 48 primary healthcare. PARTICIPANTS: 8902 patients had an HF diagnosis based on the International Classification of Diseases, Tenth Revision during the study period. Patients <18 years as well as patients declining to participate were excluded resulting in a study population of 8775 patients. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was distribution of HF phenotypes by echocardiography. The secondary outcome measures were 1 year all-cause mortality and HR for all-cause mortality using Cox regression models. RESULTS: Out of 8775 patients with HF, 5023 (57%) had a conclusive echocardiography distributed into HF with reduced EF (35%), HF with mildly reduced EF (27%) and HF with preserved EF (38%). A total of 43% of the cohort did not have a conclusive echocardiography, and therefore no defined phenotype (HF-NDP). One-year all-cause mortality was 42% within the HF-NDP group and 30% among those with a conclusive EF. The HR of all-cause mortality in the HF-NDP group was 1.27 (95% CI 1.17 to 1.37) when compared with the confirmed EF group. There was no significant difference in survival within the HF phenotypes. CONCLUSIONS: This population-based study showed a distribution of HF phenotypes that varies from those in selected HF registries, with fewer patients with HF with reduced EF and more patients with HF with preserved EF. Furthermore, 1-year all-cause mortality was significantly higher among patients with HF who had not undergone a conclusive echocardiography at diagnosis, highlighting the importance of correct diagnostic procedure to improve treatment strategies and outcomes

Cost-effectiveness of pharmacogenetic testing to predict treatment response to angiotensin-converting enzyme inhibitor

OBJECTIVE: This study aimed to assess the potential cost-effectiveness of testing patients with nephropathies for the I/D polymorphism before starting angiotensin-converting enzyme (ACE) inhibitor therapy, using a 3-year time horizon and a healthcare perspective. METHODS: We used a combination of a decision analysis and Markov modeling technique to evaluate the potential economic value of this pharmacogenetic test by preventing unfavorable treatment in patients with nephropathies. The estimation of the predictive value of the I/D polymorphism is based on a systematic review showing that DD carriers tend to respond well to ACE inhibitors, while II carriers seem not to benefit adequately from this treatment. Data on the ACE inhibitor effectiveness in nephropathy were derived from the REIN (Ramipril Efficacy in Nephropathy) trial. We calculated the number of patients with end-stage renal disease (ESRD) prevented and the differences in the incremental costs and incremental effect expressed as life-years free of ESRD. A probabilistic sensitivity analysis was conducted to determine the robustness of the results. RESULTS: Compared with unselective treatment, testing patients for their ACE genotype could save 12 patients per 1000 from developing ESRD during the 3 years covered by the model. As the mean net cost savings was euro 356,000 per 1000 patient-years, and 9 life-years free of ESRD were gained, selective treatment seems to be dominant. CONCLUSION: The study suggests that genetic testing of the I/D polymorphism in patients with nephropathy before initiating ACE therapy will most likely be cost-effective, even if the risk for II carriers to develop ESRD when treated with ACE inhibitors is only 1.4% higher than for DD carriers. Further studies, however, are required to corroborate the difference in treatment response between ACE genotypes, before genetic testing can be justified in clinical practice

Healthcare resource utilisation and costs associated with a heart failure diagnosis : a retrospective, population-based cohort study in Sweden

Objectives To examine healthcare resource use (HRU) and costs among heart failure (HF) patients using population data from Sweden. Design Retrospective, non-interventional cohort study. Setting Two cohorts were identified from linked national health registers (cohort 1, 2005-2014) and electronic medical records (cohort 2, 2010-2012; primary/secondary care patients from Uppsala and Vasterbotten). Participants Patients (aged &gt;= 18 years) with primary or secondary diagnoses of HF (&gt;= 2 International Classification of Diseases and Related Health Problems, 10th revision classification) during the identification period of January 2005 to March 2015 were included. Outcome measures HRU across the HF phenotypes was assessed with logistic regression. Costs were estimated based on diagnosis-related group codes and general price lists. Results Total annual costs of secondary care of prevalent HF increased from SEK 6.23 (euro0.60) to 8.86 (euro0.85) billion between 2005 and 2014. Of 4648 incident patients, HF phenotype was known for 1715: reduced ejection fraction (HFrEF): 64.5%, preserved ejection fraction (HFpEF): 35.5%. Within 1 year of HF diagnosis, the proportion of patients hospitalised was only marginally higher for HFrEF versus HFpEF (all-cause (95% CI): 64.7% (60.8 to 68.4) vs 63.7% (60.8 to 66.5), HR 0.91, p=0.14; cardiovascular disease related (95% CI): 61.1% (57.1 to 64.8) vs 60.9% (58.0 to 63.7), HR 0.93, p=0.28). Frequency of hospitalisations and outpatient visits per patient declined after the first year. All-cause secondary care costs in the first year were SEK 122 758 (euro12 890)/patient/year, with HF-specific care accounting for 69% of the costs. Overall, 10% of the most expensive population (younger; predominantly male; more likely to have comorbidities) incurred similar to 40% of total secondary care costs. Conclusions HF-associated costs and HRU are high, especially during the first year of diagnosis. This is driven by high hospitalisations rates. Understanding the profile of resource-intensive patients being at younger age, male sex and high Charlson comorbidity index scores at the time of the HF diagnosis is most likely a sign of more severe disease

Economic burden of COPD in a Swedish cohort : the ARCTIC study

Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting. Patients and methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed. Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population ((sic)13,179) versus the reference population ((sic)2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (similar to(sic)28,000 per patient) were the largest economic burden in COPD patients of working age during 2013. Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease

Implementation of sacubitril/valsartan in Sweden : clinical characteristics, titration patterns, and determinants

Aims: The aim of this study is to study the introduction of sacubitril/valsartan (sac/val) in Sweden with regards to regional differences, clinical characteristics, titration patterns, and determinants of use and discontinuation. Methods and results: A national cohort of heart failure was defined from the Swedish Prescribed Drug Register and National Patient Register. A subcohort with additional data from the Swedish Heart Failure Registry (SwedeHF) was also studied. Cohorts were subdivided as per sac/val prescription and registration in SwedeHF. Median sac/val prescription rate was 20 per 100 000 inhabitants. Between April 2016 and December 2017, we identified 2037 patients with &gt;= 1 sac/val prescription, of which 1144 (56%) were registered in SwedeHF. Overall, patients prescribed with sac/val were younger, more frequently male, and had less prior cardiovascular disease than non-sac/val patients. In SwedeHF subcohort, patients prescribed with sac/val had lower ejection fraction. Overall, younger age [hazard ratio 2.81 (95% confidence interval 2.45-3.22)], registration in SwedeHF [1.97 (1.83-2.12)], male gender [1.50 (1.37-1.64)], ischaemic heart disease [1.50 (1.39-1.62)], lower left ventricular ejection fraction [3.06 (2.18-4.31)], and New York Heart Association IV [1.50 (1.22-1.84)] were predictors for sac/val use. As initiation dose in the sac/val cohort, 38% received 24/26 mg, 54% 49/51 mg, and 9% 97/103 mg. Up-titration to the target dose was achieved in 57% of the overall cohort over a median follow-up of 6 months. The estimated treatment persistence for any dose at 360 days was 82%. Conclusions: Implementation of sac/val in Sweden was slow and varied five-fold across different regions; younger age, male, SwedeHF registration, and ischaemic heart disease were among the independent predictors of receiving sac/val. Overall, treatment persistence and tolerability was high

Indacaterol/glycopyrronium is cost-effective compared to salmeterol/fluticasone in COPD : FLAME-based modelling in a Swedish population

Background: This study assessed the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD) patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year. Methods: A previously published and validated patient-level simulation model was adapted using clinical data from the FLAME trial and real-world cost data from the ARCTIC study. Costs (total monetary costs comprising drug, maintenance, exacerbation, and pneumonia costs) and health outcomes (life-years (LYs), quality-adjusted life-years (QALYs)) were projected over various time horizons (1, 5, 10 years, and lifetime) from the Swedish payer's perspective and were discounted at 3% annually. Uncertainty in model input values was studied through one-way and probabilistic sensitivity analyses. Subgroup analyses were also performed. Results: IND/GLY was associated with lower costs and better outcomes compared with SFC over all the analysed time horizons. Use of IND/GLY resulted in additional 0.192 LYs and 0.134 QALYs with cost savings of €1211 compared with SFC over lifetime. The net monetary benefit (NMB) was estimated to be €8560 based on a willingness-to-pay threshold of €55,000/QALY. The NMB was higher in the following subgroups: severe (GOLD 3), high risk and more symptoms (GOLD D), females, and current smokers. Conclusion: IND/GLY is a cost-effective treatment compared with SFC in COPD patients with mMRC dyspnea grade ≥ 2, moderate to very severe airflow limitation, and ≥1 exacerbation in the preceding year

Indacaterol/glycopyrronium (IND/GLY) is cost-effective compared with salmeterol/fluticasone (SFC) in Swedish chronic obstructive pulmonary disease (COPD) patients

Introduction/Aim: Results from the recent one-year FLAME study demonstrated superior efficacy of IND/GLY over SFC in reducing the annual rate of moderate and severe exacerbations in COPD patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year. This economic evaluation aims to determine whether this clinical effect translates into health economic benefits using a cost-effectiveness analysis from the Swedish payer’s perspective. Methods: A previously published and validated patient-level simulation model was updated with population and clinical data from the FLAME study and exacerbation and maintenance cost data from the real-world retrospective ARCTIC Swedish cohort study (n=18,586). Both direct costs and benefits were analyzed over various time horizons and were discounted at 3% per annum. Here, we present results for the time horizon of 3 years. Results: IND/GLY was associated with lower total direct costs and better outcomes compared with SFC over the time horizon of 3 years. Results showed that the use of IND/GLY over SFC resulted in an incremental gain in 0.008 quality-adjusted life-years and 0.005 life-years with cost savings of €732 per patient. The average number of moderate and severe exacerbations per patient was predicted lower with the use of IND/GLY compared with SFC at 3 years (1.98 vs. 2.39). Conclusion: This cost-effectiveness analysis showed that treatment with IND/GLY is more effective and less costly compared to treatment with SFC in Swedish COPD patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year

Additional file 1: of Indacaterol/glycopyrronium is cost-effective compared to salmeterol/fluticasone in COPD: FLAME-based modelling in a Swedish population

Methods and Results (additional details) (ZIP 535 kb