| 1. |
- Bang, Casper N., et al.
(författare)
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Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis : The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study
- 2012
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 163:4, s. 690-696
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Tidskriftsartikel (refereegranskat)abstract
- Background Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS). Methods Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1: 1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events. Results During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P < .001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P < .001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03). Conclusions Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis. (Am Heart J 2012;163:690-6.)
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| 2. |
- Bang, Casper N., et al.
(författare)
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Renin-angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis
- 2014
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 175:3, s. 492-498
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renin-angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS. Methods: All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses. Results: 769 (41%) patients received RASI. During a median follow-up of 4.3 +/- 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95% CI: 0.50-2.83], p = 0.694), cardiovascular (HR: 1.05 [95% CI: 0.62-1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95% CI: 0.55-1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040). Conclusions: RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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| 3. |
- 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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| 4. |
- Greve, Anders M., et al.
(författare)
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Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis : The SEAS study
- 2015
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 180, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- Background: An elevated resting heart rate (RHR) may be an early sign of cardiac failure, but its prognostic value during watchful waiting in asymptomatic aortic stenosis (AS) is largely unknown. Methods: RHR was determined by annual ECGs in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study of asymptomatic mild-to-moderate AS patients. Primary endpoint in this substudy was major cardiovascular events (MCEs) and secondary outcomes its individual components. Multivariable Cox-models using serially-measured RHR were used to examine the prognostic impact of RHR per se. Results: 1563 patients were followed for a mean of 4.3 years (6751 patient-years of follow-up), 553 (35%) MCEs occurred, 10% (n = 151) died, including 75 cardiovascular deaths. In multivariable analysis, baseline RHR was independently associated with MCEs (HR 1.1 per 10 min(-1) faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10 min(-1) faster, 95% CI: 1.0-1.7, both p <= 0.03). Updating RHR with annual in-study reexaminations, time-varying RHR was highly associated with excess MCEs (HR 1.1 per 10 min(-1) faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10 min(-1) faster, 95% CI: 1.2-1.7, both p <= 0.006). The association of RHR with MCEs and cardiovascular mortality was not dependent on atrial fibrillation status (both p >= 0.06 for interaction). Conclusions: RHR is independently associated with MCEs and cardiovascular death in asymptomatic AS (Clinicaltrials.gov; unique identifier NCT00092677).
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