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1.
Can J Cardiol ; 37(4): 531-546, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827756

RESUMO

In this update of the Canadian Cardiovascular Society heart failure (HF) guidelines, we provide comprehensive recommendations and practical tips for the pharmacologic management of patients with HF with reduced ejection fraction (HFrEF). Since the 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of HF, substantial new evidence has emerged that has informed the care of these patients. In particular, we focus on the role of novel pharmacologic therapies for HFrEF including angiotensin receptor-neprilysin inhibitors, sinus node inhibitors, sodium glucose transport 2 inhibitors, and soluble guanylate cyclase stimulators in conjunction with other long established HFrEF therapies. Updated recommendations are also provided in the context of the clinical setting for which each of these agents might be prescribed; the potential value of each therapy is reviewed, where relevant, for chronic HF, new onset HF, and for HF hospitalization. We define a new standard of pharmacologic care for HFrEF that incorporates 4 key therapeutic drug classes as standard therapy for most patients: an angiotensin receptor-neprilysin inhibitor (as first-line therapy or after angiotensin converting enzyme inhibitor/angiotensin receptor blocker titration); a ß-blocker; a mineralocorticoid receptor antagonist; and a sodium glucose transport 2 inhibitor. Additionally, many patients with HFrEF will have clinical characteristics for which we recommended other key therapies to improve HF outcomes, including sinus node inhibitors, soluble guanylate cyclase stimulators, hydralazine/nitrates in combination, and/or digoxin. Finally, an approach to management that integrates prioritized pharmacologic with nonpharmacologic and invasive therapies after a diagnosis of HFrEF is highlighted.

3.
Can J Cardiol ; 37(4): 632-643, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33453357

RESUMO

The advent of newly available medical therapies for heart failure with reduced ejection fraction (HFrEF) has resulted in many potential therapeutic combinations, increasing treatment complexity. Publication of expert consensus guidelines and initiatives aimed to improve implementation of treatment has emphasized sequential stepwise initiation and titration of medical therapy, which is labour intensive. Data taken from heart failure registries show suboptimal use of medications, prolonged titration times, and consequently little change in dose intensity, all of which indicate therapeutic inertia. Recently published evidence indicates that 4 medication classes-renin-angiotensin-neprilysin inhibitors, ß-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter inhibitors-which we refer to as Foundational Therapy, confer rapid and robust reduction in both morbidity and mortality in most patients with HFrEF and that they work in additive fashion. Additional morbidity and mortality may be observed following addition of several personalized therapies in specific subgroups of patients. In this review, we discuss mechanisms of action of these therapies and propose a framework for their implementation, based on several principles. These include the critical importance of rapid initiation of all 4 Foundational Therapies followed by their titration to target doses, emphasis on multiple simultaneous drug changes with each patient encounter, attention to patient-specific factors in choice of medication class, leveraging inpatient care, use of the entire health care team, and alternative (ie, virtual visits) modes of care. We have incorporated these principles into a Cluster Scheme designed to facilitate timely and optimal medical treatment for patients with HFrEF.

5.
Eur Heart J ; 42(6): 700-710, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33351892

RESUMO

AIMS: The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF). METHODS AND RESULTS: HF patients with reduced EF (HFrEF) (≤40%, N = 312, EMPERIAL-Reduced) or preserved EF (>40%, N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were -4.0 m (-16.0, 6.0; P = 0.42) and 4.0 m (-5.0, 13.0; P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported. CONCLUSION: The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed.

6.
CJC Open ; 2(6): 447-453, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33305203

RESUMO

Background: Angiotensin receptor neprilysin inhibitor (ARNi) therapy improves clinical outcomes in patients with heart failure and reduced left ventricular ejection fraction. However, ARNi therapy uptake remains modest, potentially in part due to perceived cost considerations of early transition from angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy. Methods: We constructed a decision-analytic Markov model to assess cost-effectiveness of 3 different ARNi initiation strategies according to timing of initiation: (1) de novo, or immediate initiation at baseline, (2) Early or after 3 months, or (3) Late, or after 9 months. Initiation strategies were compared with (4) current care, with utilization of ARNi derived from a large observational database. Total costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) were estimated over a 5-year time horizon in the base case analysis. Results: Current care was associated with the lowest total cost (CAD$26,664) and accrued benefit (3.28 QALYs). The de novo strategy yielded an ICER of $34,727 per QALY gained, whereas Early and Late initiation strategies yielded a less favourable ICER per QALY gained of $35,871 and $40,234, respectively. The model was most sensitive to the cost of ARNi therapy. Conclusion: A strategy of de novo ARNi initiation is economically attractive and becomes less favourable as the delay of initiation increases. Our results suggest that ARNi therapy should be initiated as soon as possible for patients with heart failure and reduced left ventricular ejection fraction.

7.
CJC Open ; 2(6): 497-505, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33305209

RESUMO

Background: Quality improvement initiatives improve health care delivery but may be resource intensive and disrupt clinical care. An embedded heart failure order set (HFOS) within a computerized physician order-entry system may mitigate these concerns. Methods: An HFOS, based on proven interventions, was implemented within an existing computerized physician order-entry system in all adult acute-care hospitals in a single Canadian metropolitan city and interrogated between January 1, 2013 and December 31, 2015. The composite of repeat hospitalization or death within 30 days of hospital discharge and hospital length of stay were reported. Results: In total, 8969 patients were included with mean age 75.6 ± 13.5 years; 4673 (52.1%) were male. The HFOS was used in 731 (8.2%) patients. After analysis of 724 pairs of propensity-score matched cohorts, patients with HFOS use experienced a lower median length of stay (8.6 vs 9.4 days, P = 0.016) and a trend toward lower composite repeat hospitalization or death (14.5% vs 17.7%, P = 0.115, hazard ratio 0.79 (0.60-1.05). Patients with HFOS use were more likely to undergo a test for left ventricular ejection fraction (88.6% vs 76.7%, P < 0.001, and to be referred to a heart failure clinic (48.5% vs 6.3%), with similar rates of discharge prescription of beta-blockers (88.7% vs 86.3) and angiotensin-converting enzyme inhibitors (87.4% vs 89.0%). Conclusions: Use of a designated HFOS within a computerized physician order-entry system is associated with shorter hospital length of stay without increase in deaths or readmissions. These findings should be confirmed in a prospective controlled trial.

8.
N Engl J Med ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185990

RESUMO

BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).

9.
Eur J Heart Fail ; 22(11): 2160-2171, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32985088

RESUMO

AIMS: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. METHODS AND RESULTS: Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m2 (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). CONCLUSIONS: GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.

10.
Eur Heart J ; 41(36): 3402-3418, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820334

RESUMO

AIMS: Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). METHODS AND RESULTS: Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined. CONCLUSION: Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.

11.
Circulation ; 142(11): 1040-1054, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32673497

RESUMO

BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

12.
ESC Heart Fail ; 7(5): 2725-2733, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32592541

RESUMO

AIMS: The aim of this study is to determine factors associated with long-term recovery of left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF) and if further recovery also occurs in this group. METHODS AND RESULTS: Among 621 participants enrolled in the Alberta Heart Failure Etiology and Analysis Team (HEART) Study, 316 with Stage C HF underwent comprehensive imaging and biomarker testing at enrolment and at 1-year follow up. Using pre-enrolment data, HF with recovered EF (HFrecEF) was defined as an absolute improvement ≥5% in LVEF from the prior lowest LVEF value, with a final LVEF value > 35% at or prior to study baseline. Participants with all LVEF > 40% were included for comparison. Hospitalization-free survival to 5 years was performed. The median cohort age was 66 years, and time from diagnosis was 4 years; 82% were male patients. Of the 316 patients, 95 (30%) patients had HFrecEF and 56 (18%) patients pHFrEF. On multivariate analysis, only shorter duration of HF was predictive of HFrecEF status. Over 1 year, LVEF increased in the HFrecEF group 4.0% (0.15-7.90, P = 0.042) as compared with persistent HFrEF, who in turn demonstrated higher baseline serum high sensitivity Troponin-T with further increase at follow up 0.55(0.33-0.86, P = 0.011). No change in any parameter in the HFpEF/HFmrEF group at follow up was observed. CONCLUSIONS: Patients with HFrecEF demonstrate evidence of additional late improvement in LVEF and unchanged troponin levels, in contrast to those with persistent HFrEF, where LVEF does not improve and serum troponin rises over time. These data help to inform mechanisms relating to late LV remodelling.

15.
Can J Cardiol ; 36(5): 596-624, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32389335

RESUMO

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

16.
CJC Open ; 2(3): 151-160, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32462129

RESUMO

This joint Canadian Heart Failure Society and the CCS Heart Failure guidelines report has been developed to provide a pan-Canadian snapshot of the current state of clinic-based ambulatory heart failure (HF) care in Canada with specific reference to elements and processes of care associated with quality and high performing health systems. It includes the viewpoints of persons with lived experience, patient care providers, and administrators. It is imperative to build on the themes identified in this survey, through engaging all health care professionals, to develop integrated and shared care models that will allow better patient outcomes. Several patient and organizational barriers to care were identified in this survey, which must inform the development of regional care models and pragmatic solutions to improve transitions for this patient population. Unfortunately, we were unsuccessful in incorporating the perspectives of primary care providers and internal medicine specialists who provide the majority of HF care in Canada, which in turn limits our ability to comment on strategies for capacity building outside the HF clinic setting. These considerations must be taken into account when interpreting our findings. Engaging all HF care providers, to build on the themes identified in this survey, will be an important next step in developing integrated and shared care models known to improve patient outcomes.

17.
Can J Cardiol ; 36(3): 322-334, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32145862

RESUMO

Cardiac amyloidosis is an under-recognized and potentially fatal cause of heart failure and other cardiovascular manifestations. It is caused by deposition of misfolded precursor proteins as fibrillary amyloid deposits in cardiac tissues. The two primary subtypes of systemic amyloidosis causing cardiac involvement are immunoglobulin light chain (AL), a plasma cell dyscrasia, and transthyretin (ATTR), itself subdivided into a hereditary subtype caused by a gene mutation of the ATTR protein, and an age-related wild type, which occurs in the absence of a gene mutation. Clinical recognition requires a high index of suspicion, inclusive of the extracardiac manifestations of both subtypes. Diagnostic workup includes screening for serum and/or urine monoclonal protein suggestive of immunoglobulin light chains, along with serum cardiac biomarker measurement and performance of cardiac imaging for findings consistent with amyloid infiltration. Modern cardiac imaging techniques, including the use of nuclear scintigraphy with bone-seeking radiotracer to noninvasively diagnose ATTR cardiac amyloidosis, have reduced reliance on the gold standard endomyocardial biopsy. Disease-modifying therapeutic approaches have evolved significantly, particularly for ATTR, and pharmacologic therapies that slow or halt disease progression are becoming available. This Canadian Cardiovascular Society/Canadian Heart Failure Society joint position statement provides evidence-based recommendations that support the early recognition and optimal diagnostic approach and management strategies for patients with cardiac amyloidosis. This includes recommendations for the symptomatic management of heart failure and other cardiovascular complications such as arrhythmia, risk stratification, follow-up surveillance, use of ATTR disease-modifying therapies, and optimal clinical care settings for patients with this complex multisystem disease.


Assuntos
Amiloidose/diagnóstico , Amiloidose/terapia , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Algoritmos , Humanos
18.
Can J Cardiol ; 36(3): 432-440, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32145870

RESUMO

BACKGROUND: Right heart function is an important prognostic determinant in cardiac amyloidosis. In this study we characterized serial changes in right and left heart function and evaluated their prognostic significance. METHODS: Cardiac amyloidosis patients with baseline and follow-up echocardiograms were included. Right and left heart function measured at baseline, 1 year, and most recent follow-up were compared and correlated with all-cause mortality or cardiovascular hospitalization. RESULTS: Ninety-three patients were included; 36 (39%) with light chain amyloidosis and 57 (61%) with transthyretin amyloidosis. Among measures of right heart function for the study population and light chain and transthyretin amyloidosis subtypes, only absolute right ventricular (RV) free wall longitudinal strain (FWLS) changed significantly from baseline to 1 year and most recent follow-up echocardiogram. After a median of 26 months (range, 14-35 months), 21 (22%) patients died and 17 (18%) had a cardiovascular hospitalization. Baseline RV FWLS was significantly associated with the primary endpoint (hazard ratio, 1.2 per % change; 95% confidence interval, 0.8-2.6; P < 0.01), whereas change from baseline to 1 year was not for any measure of right heart function. Baseline left ventricular (LV) global longitudinal strain (GLS) and 1 year change were significantly associated with the primary end point. Change in RV FWLS at 1 year was significantly correlated with baseline LV GLS (r = 0.68; P = 0.01) and change at 1 year follow-up (r = 0.72; P < 0.01). CONCLUSIONS: In cardiac amyloidosis patients, baseline RV FWLS was associated with adverse outcomes whereas changes at follow-up was not. Change in RV FWLS was significantly correlated with baseline and follow-up change in LV GLS, possibly reflecting progressive biventricular amyloid deposition.


Assuntos
Amiloidose/mortalidade , Amiloidose/fisiopatologia , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Idoso , Feminino , Testes de Função Cardíaca , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
19.
Eur Heart J ; 41(25): 2379-2392, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32221582

RESUMO

AIMS: In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy. METHODS AND RESULTS: In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and <50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n = 4744) were treated with a diuretic (84%), renin-angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65-0.85] for the primary composite endpoint (P < 0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61-0.86) compared with 0.77 (95% CI 0.63-0.94) in those not on all three of these treatments (P-interaction 0.64). CONCLUSION: The benefit of dapagliflozin was consistent regardless of background therapy for HF.

20.
Can J Cardiol ; 36(2): 159-169, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32036861

RESUMO

In this update, we focus on selected topics of high clinical relevance for health care providers who treat patients with heart failure (HF), on the basis of clinical trials published after 2017. Our objective was to review the evidence, and provide recommendations and practical tips regarding the management of candidates for the following HF therapies: (1) transcatheter mitral valve repair in HF with reduced ejection fraction; (2) a novel treatment for transthyretin amyloidosis or transthyretin cardiac amyloidosis; (3) angiotensin receptor-neprilysin inhibition in patients with HF and preserved ejection fraction (HFpEF); and (4) sodium glucose cotransport inhibitors for the prevention and treatment of HF in patients with and without type 2 diabetes. We emphasize the roles of optimal guideline-directed medical therapy and of multidisciplinary teams when considering transcatheter mitral valve repair, to ensure excellent evaluation and care of those patients. In the presence of suggestive clinical indices, health care providers should consider the possibility of cardiac amyloidosis and proceed with proper investigation. Tafamidis is the first agent shown in a prospective study to alter outcomes in patients with transthyretin cardiac amyloidosis. Patient subgroups with HFpEF might benefit from use of sacubitril/valsartan, however, further data are needed to clarify the effect of this therapy in patients with HFpEF. Sodium glucose cotransport inhibitors reduce the risk of incident HF, HF-related hospitalizations, and cardiovascular death in patients with type 2 diabetes and cardiovascular disease. A large clinical trial recently showed that dapagliflozin provides significant outcome benefits in well treated patients with HF with reduced ejection fraction (left ventricular ejection fraction ≤ 40%), with or without type 2 diabetes.


Assuntos
Amiloidose/complicações , Amiloidose/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Benzoxazóis/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Neprilisina/antagonistas & inibidores , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Cardiopatias/complicações , Cardiopatias/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Insuficiência da Valva Mitral/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Volume Sistólico
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