المؤلفون: Shen, L., Claggett, B. L., Jhund, P. S., Abraham, W. T., Desai, A. S., Dickstein, K., Gong, J. J., Kober, L. V., Lefkowitz, M. P., Rouleau, J. L., Shi, V. C., Swedberg, Karl, 1944, Zile, M. R., Solomon, S. D., McMurray, J. J. V.

المصدر: Clinical Research in Cardiology. 110:1334-1349

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, Sudden death, Pump failure death, Model, Risk, Heart failure, Device, seattle heart-failure, implantable cardioverter-defibrillator, risk, score, proportional risk, mortality, survival, outcomes, morbidity, enalapril, Cardiovascular System & Cardiology

الوصف: Background Sudden death (SD) and pump failure death (PFD) are the two leading causes of death in patients with heart failure and reduced ejection fraction (HFrEF). Objective Identifying patients at higher risk for mode-specific death would allow better targeting of individual patients for relevant device and other therapies. Methods We developed models in 7156 patients with HFrEF from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, using Fine-Gray regressions counting other deaths as competing risks. The derived models were externally validated in the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure (ATMOSPHERE) trial. Results NYHA class and NT-proBNP were independent predictors for both modes of death. The SD model additionally included male sex, Asian or Black race, prior CABG or PCI, cancer history, MI history, treatment with LCZ696 vs. enalapril, QRS duration and ECG left ventricular hypertrophy. While LVEF, ischemic etiology, systolic blood pressure, HF duration, ECG bundle branch block, and serum albumin, chloride and creatinine were included in the PFD model. Model discrimination was good for SD and excellent for PFD with Harrell's C of 0.67 and 0.78 after correction for optimism, respectively. The observed and predicted incidences were similar in each quartile of risk scores at 3 years in each model. The performance of both models remained robust in ATMOSPHERE. Conclusion We developed and validated models which separately predict SD and PFD in patients with HFrEF. These models may help clinicians and patients consider therapies targeted at these modes of death.

URL الوصول: https://gup.ub.gu.se/publication/306986

المؤلفون: Rohde, L. E., Claggett, B. L., Wolsk, E., Packer, M., Zile, M., Swedberg, Karl, 1944, Rouleau, J., Pfeffer, M. A., Desai, A. S., Lund, L. H., Kober, L., Anand, I., Merkely, B., Senni, M., Shi, V., Rizkala, A., Lefkowitz, M., McMurray, J. J. V., Solomon, S. D.

المصدر: Circulation-Heart Failure. 14(3):361-371

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, heart failure, mortality, prognosis, therapeutics, Cardiovascular System & Cardiology

الوصف: Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan across the spectrum of left ventricular ejection fraction. Methods: We combined data from 2 global trials that evaluated the efficacy of sacubitril/valsartan compared with a renin-angiotensin antagonist in symptomatic HF patients (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure; n=8399] and PARAGON-HF [Prospective Comparison of Angiotensin-Converting Enzyme Inhibitor With Angiotensin Receptors Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction; n=4796]). We decomposed the previously validated Meta-Analysis Global Group in Chronic Heart Failure risk score into cardiac (left ventricular ejection fraction, New York Heart Association class, blood pressure, time since HF diagnosis, HF medications), noncardiac comorbid (body mass index, creatinine, diabetes, chronic obstructive pulmonary disease, smoking), and demographic (age, gender) categories. Based on these domains, an index representing the balance of cardiac to noncardiac comorbid burden was created (cardiac-comorbid index). Clinical outcomes were time to first HF hospitalization or cardiovascular deaths and all-cause mortality. Results: Higher scores of the cardiac domain were observed in PARADIGM-HF (10 [7-13] versus 5 [3-6], P<0.001) and higher scores of the demographic domain in PARAGON-HF (10 [8-13] versus 5 [2-9], P<0.001). In PARADIGM-HF, the contribution of the cardiac domain to clinical outcomes was greater than the noncardiac domain (P<0.001), while in PARAGON-HF the attributable risk of the comorbid and demographic categories predominated. Individual scores from each sub-domain were linearly associated with the risk of clinical outcomes (P<0.001). Beneficial effects of sacubitril/valsartan were observed in patients with preponderance of cardiac over noncardiac comorbid burden (cardiac-comorbid index >5 points), suggesting a significant treatment effect modification (interaction P<0.05 for both outcomes). Conclusions: Domains of disease burden are clinically relevant features that influence the prognosis and treatment of patients with HF. The therapeutic benefits of sacubitril/valsartan vary according to the balance of components of disease burden, across different ranges of left ventricular ejection fraction.

URL الوصول: https://gup.ub.gu.se/publication/304998

المؤلفون: Selvaraj, S., Claggett, B., Pozzi, A., McMurray, J. J. V., Jhund, P. S., Packer, M., Desai, A. S., Lewis, E. F., Vaduganathan, M., Lefkowitz, M. P., Rouleau, J. L., Shi, V. C., Zile, M. R., Swedberg, Karl, 1944, Solomon, S. D.

المصدر: Circulation. 140(17):1369-1379

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, congestion, congestive heart failure, physical exam, sacubitril, valsartan, peptide-guided therapy, high-risk, hospitalization, hemodynamics, signs, care, mortality, enalapril, symptoms, survival, Cardiovascular System & Cardiology

الوصف: AbstractBackground:The contemporary prognostic value of the physical examination— beyond traditional risk factors including natriuretic peptides, risk scores, and symptoms—in heart failure (HF) with reduced ejection fraction is unknown. We aimed to determine the association between physical signs of congestion at baseline and during study follow-up with quality of life and clinical outcomes and to assess the treatment effects of sacubitril/valsartan on congestion.Methods:We analyzed participants from PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) with an available physical examination at baseline. We examined the association of the number of signs of congestion (jugular venous distention, edema, rales, and third heart sound) with the primary outcome (cardiovascular death or HF hospitalization), its individual components, and all-cause mortality using time-updated, multivariable-adjusted Cox regression. We further evaluated whether sacubitril/valsartan reduced congestion during follow-up and whether improvement in congestion is related to changes in clinical outcomes and quality of life, assessed by Kansas City Cardiomyopathy Questionnaire overall summary scores.Results:Among 8380 participants, 0, 1, 2, and 3+ signs of congestion were present in 70%, 21%, 7%, and 2% of patients, respectively. Patients with baseline congestion were older, more often female, had higher MAGGIC risk scores (Meta-Analysis Global Group in Chronic Heart Failure) and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (P<0.05). After adjusting for baseline natriuretic peptides, time-updated Meta-Analysis Global Group in Chronic Heart Failure score, and time-updated New York Heart Association class, increasing time-updated congestion was associated with all outcomes (P<0.001). Sacubitril/valsartan reduced the risk of the primary outcome irrespective of clinical signs of congestion at baseline (P=0.16 for interaction), and treatment with the drug improved congestion to a greater extent than did enalapril (P=0.011). Each 1-sign reduction was independently associated with a 5.1 (95% CI, 4.7–5.5) point improvement in Kansas City Cardiomyopathy Questionnaire overall summary scores. Change in congestion strongly predicted outcomes even after adjusting for baseline congestion (P<0.001).Conclusions:In HF with reduced ejection fraction, the physical exam continues to provide significant independent prognostic value even beyond symptoms, natriuretic peptides, and Meta-Analysis Global Group in Chronic Heart Failure risk score. Sacubitril/valsartan improved congestion to a greater extent than did enalapril. Reducing congestion in the outpatient setting is independently associated with improved quality of life and reduced cardiovascular events, including mortality.

URL الوصول: https://gup.ub.gu.se/publication/285341

المؤلفون: Vardeny, O., Claggett, B., Kachadourian, J., Desai, A. S., Packer, M., Rouleau, J., Zile, M. R., Swedberg, Karl, 1944, Lefkowitz, M., Shi, V., McMurray, J. J. V., Solomon, S. D.

المصدر: European Journal of Heart Failure. 21(3):337-341

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, Diuretics, Randomized clinical trial, Heart failure with reduced ejection fraction, Sacubitril/valsartan, Enalapril, progressive heart-failure, death, hospitalization, inhibition, neprilysin, mortality, system, Cardiovascular System & Cardiology

الوصف: Aims To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. Methods and results Overall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2mg for sacubitril/valsartan and 49.6mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24months, respectively, with similar findings in an on-treatment analysis. Conclusion Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

URL الوصول: https://gup.ub.gu.se/publication/279673

المؤلفون: Ehteshami-Afshar, S., Mooney, L., Dewan, P., Desai, A. S., Lang, N. N., Lefkowitz, M. P., Petrie, M. C., Rizkala, A. R., Rouleau, J. L., Solomon, S. D., Swedberg, Karl, 1944, Shi, V. C., Zile, M. R., Packer, M., McMurray, J. J. V., Jhund, P. S., Hawkins, N. M.

المصدر: Journal of the American Heart Association. 10(4)

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, chronic obstructive pulmonary disease, ejection fraction, heart failure, hospitalization, mortality, neprilysin, right ventricle, Cardiovascular System & Cardiology

الوصف: BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. METHODS AND RESULTS: We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non-COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P<0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; P<0.001) and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (73 versus 81; P<0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta-blockade (87% versus 94%; P<0.001) and diuretics (85% versus 80%; P<0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13-1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05-1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94-1.30), or all-cause mortality (HR, 1.14; 95% CI, 0.99-1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05-1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29-1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. CONCLUSIONS: In PARADIGM-HF, COPD was associated with lower use of beta-blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high-risk subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01035255.

URL الوصول: https://gup.ub.gu.se/publication/302623

المؤلفون: Desai, A. S., Claggett, B. L., Packer, M., Zile, M. R., Rouleau, J. L., Swedberg, Karl, 1944, Shi, V., Lefkowitz, M., Starling, R., Teerlink, J., McMurray, J. J. V., Solomon, S. D.

المصدر: Journal of the American College of Cardiology. 68(3):242-248

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, hospitalization, neprilysin, readmission, sacubitril/valsartan, all-cause readmission, medicare beneficiaries, neprilysin inhibition, care, association, population, guidelines, enalapril, statement, mortality, Cardiovascular System & Cardiology

الوصف: BACKGROUND Patients with heart failure (HF) are at high risk for hospital readmission in the first 30 days following HF hospitalization. OBJECTIVES This study sought to determine if treatment with sacubitril/valsartan (LCZ696) reduces rates of hospital readmission at 30-days following HF hospitalization compared with enalapril. METHODS We assessed the risk of 30-day readmission for any cause following investigator-reported hospitalizations for HF in the PARADIGM-HF trial, which randomized 8,399 participants with HF and reduced ejection fraction to treatment with LCZ696 or enalapril. RESULTS Accounting for multiple hospitalizations per patient, there were 2,383 investigator-reported HF hospitalizations, of which 1,076 (45.2%) occurred in subjects assigned to LCZ696 and 1,307 (54.8%) occurred in subjects assigned to enalapril. Rates of readmission for any cause at 30 days were 17.8% in LCZ696-assigned subjects and 21.0% in enalapril-assigned subjects (odds ratio: 0.74; 95% confidence interval: 0.56 to 0.97; p = 0.031). Rates of readmission for HF at 30-days were also lower in subjects assigned to LCZ696 (9.7% vs. 13.4%; odds ratio: 0.62; 95% confidence interval: 0.45 to 0.87; p = 0.006). The reduction in both all-cause and HF readmissions with LCZ696 was maintained when the time window from discharge was extended to 60 days and in sensitivity analyses restricted to adjudicated HF hospitalizations. CONCLUSIONS Compared with enalapril, treatment with LCZ696 reduces 30-day readmissions for any cause following discharge from HF hospitalization.

URL الوصول: https://gup.ub.gu.se/publication/239619

المؤلفون: Okumura, N., Jhund, P. S., Gong, J. J., Lefkowitz, M. P., Rizkala, A. R., Rouleau, J. L., Shi, V. C., Swedberg, Karl, 1944, Zile, M. R., Solomon, S. D., Packer, M., McMurray, J. J. V.

المصدر: Circulation. 133(23):2254-2262

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, emergency service, hospital, heart failure, hospitalization, mortality, neprilysin, sacubitril/valsartan, emergency-department, neprilysin inhibition, hospital readmission, subsequent mortality, care, enalapril, inpatient, outcomes, therapy, risk, Cardiovascular System & Cardiology

الوصف: Background-Many episodes of worsening of heart failure (HF) are treated by increasing oral therapy or temporary intravenous treatment in the community or emergency department (ED), without hospital admission. We studied the frequency and prognostic importance of these episodes of worsening in the Prospective Comparison of ARNI (angiotensin-receptor-neprilysin inhibitor) with ACEI (angiotensin-converting enzyme inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF). Methods and Results-Outpatient intensification of HF therapy was added to an expanded composite outcome with ED visits, HF hospitalizations, and cardiovascular deaths. In an examination of first nonfatal events, 361 of 8399 patients (4.3%) had outpatient intensification of HF therapy without a subsequent event (ie, ED visit/HF hospitalizations) within 30 days; 78 of 8399 (1.0%) had an ED visit without previous outpatient intensification of HF therapy or a subsequent event within 30 days; and 1107 of 8399 (13.2%) had HF hospitalizations without a preceding event. The risk of death (in comparison with no-event patients) was similar after each manifestation of worsening: outpatient intensification of HF therapy (hazard ratio, 4.8; 95% confidence interval, 3.9-5.9); ED visit (hazard ratio, 4.5; 95% confidence interval, 3.0-6.7); HF hospitalizations (hazard ratio, 5.9; 95% confidence interval, 5.2-6.6). The expanded composite added 14% more events and shortened time to accrual of a fixed number of events. The benefit of sacubitril/valsartan over enalapril was similar to the primary outcome for the expanded composite (hazard ratio, 0.79; 95% confidence interval, 0.73-0.86) and was consistent across the components of the latter. Conclusions-Focusing only on HF hospitalizations underestimates the frequency of worsening and the serious implications of all manifestations of worsening. For clinical trials conducted in an era of heightened efforts to avoid HF hospitalizations, inclusion of episodes of outpatient treatment intensification (and ED visits) in a composite outcome adds an important number of events and shortens the time taken to accrue a target number of end points in an event-driven trial.

URL الوصول: https://gup.ub.gu.se/publication/238291

المؤلفون: Simpson, J., Jhund, P. S., Cardoso, J. S., Martinez, F., Mosterd, A., Ramires, F., Rizkala, A. R., Senni, M., Squire, I., Gong, J. J., Lefkowitz, M. P., Shi, V. C., Desai, A. S., Rouleau, J. L., Swedberg, Karl, 1944, Zile, M. R., McMurray, J. J. V., Packer, M., Solomon, S. D.

المصدر: Journal of the American College of Cardiology. 66(19):2059-2071

مصطلحات موضوعية: Clinical Medicine, Klinisk medicin, angiotensin receptor neprilysin inhibitor, prognostic model, risk score, survival, heart-failure, neprilysin inhibition, predicting survival, mortality, morbidity, impact, trial, Cardiovascular System & Cardiology

الوصف: BACKGROUND Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure. OBJECTIVES The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum. METHODS This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorizepatients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696. RESULTS The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p < 0.001) and a 7% increased risk for cardiovascular death (p < 0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings. CONCLUSIONS Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255)

URL الوصول: https://gup.ub.gu.se/publication/225987

المؤلفون: Jhund, P. S., Fu, M., Bayram, E., Chen, C. H., Negrusz-Kawecka, M., Rosenthal, A., Desai, A. S., Lefkowitz, M. P., Rizkala, A. R., Rouleau, J. L., Shi, V. C., Solomon, S. D., Swedberg, Karl, 1944, Zile, M. R., McMurray, J. J. V., Packer, M.

المصدر: European Heart Journal. 36(38):2576-2584

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, Heart failure, Neprilysin, Receptors, Angiotensin, Age, systolic heart-failure, clinical-trials, neprilysin inhibition, enalapril, comorbidities, management, mortality, program, risk, Cardiovascular System & Cardiology

الوصف: Background The age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age. We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Methods In PARADIGM-HF, 8399 patients aged 18-96 years and in New York Heart Association functional class II-IV with an LVEF <= 40% were randomized to either enalapril or LCZ696. We examined the pre-specified efficacy and safety outcomes according to age category (years): <55 (n = 1624), 55-64 (n = 2655), 65-74 (n = 2557), and >= 75 (n = 1563). Findings The rate (per 100 patient-years) of the primary outcome of cardiovascular (CV) death or heart failure hospitalization (HFH) increased from 13.4 to 14.8 across the age categories. The LCZ696: enalapril hazard ratio (HR) was <1.0 in all categories (P for interaction between age category and treatment = 0.94) with an overall HR of 0.80 (0.73, 0.87), P < 0.001. The findings for HFH were similar for CV and all-cause mortality and the age category by treatment interactions were not significant. The pre-specified safety outcomes of hypotension, renal impairment and hyperkalaemia increased in both treatment groups with age, although the differences between treatment (more hypotension but less renal impairment and hyperkalaemia with LCZ696) were consistent across age categories. Interpretation LCZ696 was more beneficial than enalapril across the spectrum of age in PARADIGM-HF with a favourable benefit-risk profile in all age groups.

URL الوصول: https://gup.ub.gu.se/publication/225388

المؤلفون: Desai, A. S., McMurray, J. J. V., Packer, M., Swedberg, Karl, 1944, Rouleau, J. L., Chen, F. B., Gong, J. J., Rizkala, A. R., Brahimi, A., Claggett, B., Finn, P. V., Hartley, L. H., Liu, J. K., Lefkowitz, M., Shi, V., Zile, M. R., Solomon, S. D.

المصدر: European Heart Journal. 36(30):1990-1997

مصطلحات موضوعية: Cardiac and Cardiovascular Systems, Kardiologi, Heart failure, Clinical trial, Pharmacotherapy, Neprilysin inhibition, Angiotensin-receptor blocker, CONVERTING-ENZYME-INHIBITORS, CARDIAC-RESYNCHRONIZATION, MYOCARDIAL-INFARCTION, MORBIDITY, MORTALITY, TRIAL, SURVIVAL, DYSFUNCTION, CANDESARTAN, LISINOPRIL, Cardiac & Cardiovascular Systems

الوصف: Aims The angiotensin-receptor-neprilysin inhibitor (ARNI) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospective comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. To more completely understand the components of this mortality benefit, we examined the effect of LCZ696 on mode of death. Methods and results PARADIGM-HF was a prospective, double-blind, randomized trial in 8399 patients with chronic heart failure, New York Heart Association Class II-IV symptoms, and left ventricular ejection fraction <= 40% receiving guideline-recommended medical therapy and followed for a median of 27 months. Mode of death was adjudicated by a blinded clinical endpoints committee. The majority of deaths were cardiovascular (80.9%), and the risk of cardiovascular death was significantly reduced by treatment with LCZ (hazard ratio, HR 0.80, 95% CI 0.72-0.89, P < 0.001). Among cardiovascular deaths, both sudden cardiac death (HR 0.80, 95% CI 0.68-0.94, P = 0.008) and death due to worsening heart failure (HR 0.79, 95% CI 0.64-0.98, P = 0.034) were reduced by treatment with LCZ696 compared with enalapril. Deaths attributed to other cardiovascular causes, including myocardial infarction and stroke, were infrequent and distributed evenly between treatment groups, as were non-cardiovascular deaths. Conclusions LCZ696 was superior to enalapril in reducing both sudden cardiac deaths and deaths from worsening heart failure, which accounted for the majority of cardiovascular deaths.

URL الوصول: https://gup.ub.gu.se/publication/222789