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| 2. |
- Jander, Nikolaus, et al.
(författare)
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Outcome of Patients With Low-Gradient "Severe" Aortic Stenosis and Preserved Ejection Fraction
- 2011
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Ingår i: Circulation. - 1524-4539 .- 0009-7322. ; 123:8, s. 887-895
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Tidskriftsartikel (refereegranskat)abstract
- Background-Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area <1.0 cm(2) and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient "severe" stenosis (defined as aortic valve area < 1.0 cm(2) and mean gradient <= 40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Methods and Results-Outcome in patients with low-gradient "severe" aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm(2); mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67 +/- 10 years; ejection fraction, >= 55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182 +/- 64 versus 212 +/- 68 g; P < 0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively (P=0.37; major cardiovascular events, 50.9% versus 48.5%, P=0.58; cardiovascular death, 7.8% versus 4.9%, P=0.19). Low-gradient severe stenosis patients with reduced stroke volume index (<= 35 mL/m(2); n=223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%; P=0.53). Conclusions-Patients with low-gradient "severe" aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis. (Circulation. 2011;123:887-895.)
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| 4. |
- Rossebo, Anne B., et al.
(författare)
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Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis
- 2008
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 359:13, s. 1343-1356
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results. Methods: We conducted a randomized, double-blind trial involving 1873 patients with mild-to-moderate, asymptomatic aortic stenosis. The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, aortic-valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events. Results: During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin-ezetimibe group and in 355 patients (38.2%) in the placebo group (hazard ratio in the simvastatin-ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P=0.59). Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin-ezetimibe group and in 278 patients (29.9%) in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P=0.97). Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P=0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01). Conclusions: Simvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (ClinicalTrials.gov number, NCT00092677.).
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| 6. |
- Greve, Anders M., et al.
(författare)
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Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study)
- 2018
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 121:6, s. 739-745
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Tidskriftsartikel (refereegranskat)abstract
- Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p >= 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p In conclusion, in a non prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677).
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| 7. |
- Greve, Anders M., et al.
(författare)
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Prognostic importance of atrial fibrillation in asymptomatic aortic stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis study
- 2013
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 166:1, s. 72-76
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Tidskriftsartikel (refereegranskat)abstract
- Background: The frequency and prognostic importance of atrial fibrillation (AF) in asymptomatic mild-to-moderate aortic stenosis (AS) has not been well described. Methods: Clinical examination, electrocardiography and echocardiography were obtained in asymptomatic patients with mild-to-moderate AS and preserved left ventricular (LV) systolic function, randomized to simvastatin/ezetimibe combination vs. placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. At inclusion, AF was categorized as episodic or longstanding. Rhythm change was assessed on annual in-study electrocardiograms. Impact of AF on cardiovascular morbidity and mortality was determined by adjusting for biomarkers, clinical- and echocardiographic covariates. Results: Mean follow-up was 4.3 +/- 0.8 years (6,721 patient-years of follow-up). At baseline, episodic AF was present in 87 patients (5.6%), longstanding AF in 55 (3.5%) and no AF in 1,421 (90.9%). Incidence of new-onset AF was 1.2%/year; highest in those with impaired LV function. In multivariable analysis, longstanding AF was compared to no AF at baseline, associated with a 4.1-fold higher risk of heart failure (CI 1.2 to 13.8, p = 0.02) and a 4.8-fold higher risk of non-hemorrhagic stroke (CI 1.7 to 13.6, p = 0.003). Conclusion: Rate of AF is moderate in asymptomatic AS. Longstanding but not episodic AF was, independently predictive of increased risk of heart failure and non-hemorrhagic stroke. New-onset AF was associated with cardiac decompensation. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 8. |
- Greve, Anders M., et al.
(författare)
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Relation of Lipid-Lowering Therapy to Need for Aortic Valve Replacement in Patients With Asymptomatic Mild to Moderate Aortic Stenosis
- 2019
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 124:11, s. 1736-1740
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we aimed to determine if pretreatment low-density lipoprotein (LDL) levels and aortic stenosis (AS) severity alter the efficacy of lipid-lowering therapy on reducing aortic valve replacement (AVR). We used 1,687 patients with asymptomatic mild-to-moderate AS, who were randomly assigned (1:1) to 40/10 mg simvastatin/ezetimibe combination versus. placebo in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial. Pretreatment LDL levels (>4 mmol/L) and peak aortic jet velocity (3 m/s) were used to partition study participants into 4 groups, which were followed for a primary endpoint of AVR. Cox regression with tests for interaction was used to study the effect of randomized treatment in each subgroup. During a median follow-up of 43 years (IQR 4.2 to 4.7 years; total 7,396 patient-years of follow-up), 478 (28%) patients underwent AVR and 146 (9%) died. A significant risk dependency was detected between simvastatin/ezetimibe combination, LDL levels and mild versus moderate AS on rates of AVR (p = 0.01 for interaction). In stratified analyses, randomized treatment, therefore, reduced the rate of AVR in patients with LDL levels >4 mmol and mild AS at baseline (HR 0.4; 95% CI: 0.2 to 0.9). There was no detectable effect of randomized treatment on the need for AVR in the 3 other participants subgroups. We conclude, that in a secondary analysis from a prospective randomized clinical trial, treatment with simvastatin/ezetimibe combination reduced the need for AVR in a subset of patients with mild AS and high pretreatment LDL levels.
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| 9. |
- Holme, Ingar, et al.
(författare)
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A risk score for predicting mortality in patients with asymptomatic mild to moderate aortic stenosis
- 2012
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Ingår i: Heart. - : BMJ Publishing Group Ltd & British Cardiovascular Society. - 1355-6037 .- 1468-201X. ; 98:5, s. 377-383
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Tidskriftsartikel (refereegranskat)abstract
- Background Prognostic information for asymptomatic patients with aortic stenosis (AS) from prospective studies is scarce and there is no risk score available to assess mortality. Objectives To develop an easily calculable score, from which clinicians could stratify patients into high and lower risk of mortality, using data from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Method A search for significant prognostic factors (p < 0.01) among SEAS patients was made by a combined judgemental and statistical elimination procedure to derive a set of three factors (age, gender and smoking) that were forced into the model, and four additional factors captured by the data: left-ventricular mass index, bilirubin, heart rate and natural logarithm of C reactive protein. Calibration was done by comparing observed with calculated number of deaths by tenths of calculated risk using coefficients from the simvastatin + ezetimibe group on placebo group patients. Results Discrimination was good with ROC area of 0.76 for all patients. Estimated probabilities of death were categorised into thirds. An optimised split point of estimated 5-year risk was about 15% (close to the upper 14% tertile split point), with risk 4 times as high in the upper compared to the two lower thirds. The SEAS score performed better than another established high risk score developed for other purposes. Conclusion A new seven factor model for risk stratification of patients with mild to moderate asymptomatic AS identified a high risk group for total mortality with good discrimination properties. Trial registration number ClinicalTrials.gov, NCT 00092677.
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| 10. |
- Holme, Ingar, et al.
(författare)
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Observed and predicted reduction of ischemic cardiovascular events in the Simvastatin and Ezetimibe in Aortic Stenosis trial.
- 2010
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 105:12, s. 1802-1808
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Tidskriftsartikel (refereegranskat)abstract
- In the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, combined ezetimibe (10 mg) and simvastatin (40 mg) decreased low-density lipoprotein cholesterol levels by 50% and ischemic cardiovascular event (ICE) risk by 22% compared to placebo. A larger decrease in ICE risk might have been expected for the degree of lipid-lowering observed. This analysis investigated relations between changes in lipoprotein components (LCs), and ICE risk decrease in the SEAS trial in all patients, by severity of aortic stenosis (AS), and compared to results of other clinical trials. A total of 1,570 patients with baseline aortic jet velocity (JV) data, baseline and 1-year low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B, and no ICEs during the first year were included in the analysis. Relations between on-treatment measurements of 1-year LCs and time-to-ICE occurrence were assessed in all patients and in JV tertiles (<2.8, 2.8 to 3.3, and >3.3 m/s). Observed and predicted ICE risk decreases were compared by Cox model. Decreases in LCs after 1 year of ezetimibe plus simvastatin were associated with decreased ICE risk in all patients and in the 2 lower JV tertiles (p <0.05 to <0.001) but not in tertile 3. In JV tertiles 1 and 2, ICE risk decreased by 47% and 36%, respectively, was reasonably well predicted by all LCs, and was consistent with findings from meta-regression analyses in other populations. In conclusion, the degree of lipid lowering by ezetimibe plus simvastatin may predict the extent of ICE risk decrease in patients with mild AS, but ICE risk prediction in patients with more severe AS is confounded by AS-associated cardiovascular events and a shorter interval of exposure to lipid lowering.
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