9 research outputs found

    Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry

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    Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

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    Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

    NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study

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    Objectives: This study examined the effects of sacubitril/valsartan on N-terminal pro\u2013B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response. Background: NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). Methods: Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to 641,000 pg/ml or &gt;30% from baseline. Results: In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p &lt; 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose 6549/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor\u2013naive or angiotensin receptor blocker\u2013naive, and no prior myocardial infarction. Conclusions: In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217

    Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial.

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    AIMS: The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). METHODS AND RESULTS: ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P &lt; 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium 656 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). CONCLUSION: This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM

    Eplerenone in patients with systolic heart failure and mild symptoms.

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    Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

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    BACKGROUN

    Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study

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    Aims: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF). Methods and results: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin–angiotensin–aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1–14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from. the day of discharge was Day –1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79–1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83–0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92–1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90–2.46). Conclusions: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks. Clinical Trial Registration: ClinicalTrials.gov ID: NCT02661217. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology

    Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

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    Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients
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