Match!

The Anglo-Scandinavian Cardiac Outcomes Trial: 11-year mortality follow-up of the lipid-lowering arm in the UK

Published on Oct 1, 2011in European Heart Journal24.889
· DOI :10.1093/eurheartj/ehr333
Peter S. Sever72
Estimated H-index: 72
(Imperial College London),
C.L. Chang11
Estimated H-index: 11
(Imperial College London)
+ 2 AuthorsNeil Poulter74
Estimated H-index: 74
(Imperial College London)
Sources
Abstract
The aim of this study was to determine the outcome benefits in those originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial—8 years after closure of the lipid-lowering arm (LLA) of the trial (ASCOT-LLA) among the UK population. Methods and results ASCOT-LLA was a factorially designed double-blind placebo-controlled trial of atorvastatin in 10 305 hypertensive patients enrolled into the ASCOT-Blood Pressure Lowering Arm (BPLA) of the trial and with total cholesterol con- centrations, at baseline, of ,6.5 mmol/L. ASCOT-LLA was stopped prematurely after a median 3.3-year follow-up because of a 36% relative risk reduction (RRR) in non-fatal myocardial infarction and fatal coronary heart disease (CHD) (the primary outcome) in favour of atorvastatin and a non-significant reduction in CV deaths (16%) and all-cause mortality (13%). After a further 2.2 years at the end of ASCOT-BPLA, despite extensive crossovers from and to statin usage, the RRR in all endpoints remained essentially unchanged. A median 11 years after initial randomization and � 8 years after closure of LLA, all-cause mortality (n ¼ 520 and 460 in placebo and atorvastatin, respectively) remained significantly lower in those originally assigned atorvastatin (HR 0.86, CI 0.76-0.98, P ¼ 0.02). CV deaths were fewer, but not significant (HR 0.89, CI 0.72-1.11, P ¼ 0.32) and non-CV deaths were significantly lower (HR 0.85, CI 0.73-0.99, P ¼ 0.03) in those formerly assigned atorvastatin attributed to a reduction in deaths due to infection and respiratory illness. Conclusion Legacy effects of those originally assigned atorvastatin may contribute to long-term benefits on all-cause mortality. An explanation for long-term benefits on non-CV deaths has not been established.
Figures & Tables
  • References (19)
  • Citations (81)
📖 Papers frequently viewed together
201059.10The Lancet
11 Authors (Colin Baigent, ..., Rory Collins)
3,051 Citations
341 Citations
201159.10The Lancet
7 Authors (Richard Bulbulia, ..., Rory Collins)
177 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References19
Newest
#1Peter S. Sever (Imperial College London)H-Index: 72
#2Neil Poulter (Imperial College London)H-Index: 74
Last. Naveed Sattar (Glas.: University of Glasgow)H-Index: 128
view all 8 authors...
Aims We tested whether on-statin C-reactive protein is associated with cardiovascular (CV) outcome in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Methods and results ASCOT randomized a subset of 4853 patients with total cholesterol ≤6.5 mmol/L (250 mg/dL) to atorvastatin or placebo. In a case–control study during 5.5-year follow-up, 485 CV cases were age- and sex-matched with 1367 controls. Baseline LDL-cholesterol (LDL-c) and log-transformed C-reactive protein predicted CV events [od...
47 CitationsSource
#1Adrian Schröder (LMU: Ludwig Maximilian University of Munich)H-Index: 6
#2Johannes Wollnik (LMU: Ludwig Maximilian University of Munich)H-Index: 2
Last. Andreas Zell (LMU: Ludwig Maximilian University of Munich)H-Index: 46
view all 10 authors...
Motivation: Statins are the most widely used cholesterol-lowering drugs. The primary target of statins is HMG-CoA reductase, a key enzyme in cholesterol synthesis. However, statins elicit pleitropic responses including beneficial as well as adverse effects in the liver or other organs. Today, the regulatory mechanisms that cause these pleiotropic effects are not sufficiently understood. Results: In this work, genome-wide RNA expression changes in primary human hepatocytes of six individuals were...
18 CitationsSource
#1Sze Ma ('KCL': King's College London)H-Index: 1
#2Christopher Cheng-Hwa Ma ('KCL': King's College London)H-Index: 4
Abstract Background 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are a drug class that reduce the level of cholesterol in the blood. As a result, statins are used to suppress the progression of cardiovascular disease. Evidence points to another component of statins involving the non-lipid effects of the drug class in preventing cardiovascular disease. One specific mediator of this action is the transforming growth factor β (TGF-β) superfamily. The ...
26 CitationsSource
Better evidence than can be provided by observational studies is needed to determine the association
3 CitationsSource
#1James D. Chalmers (Edin.: University of Edinburgh)H-Index: 47
#2Philip M. Short (Ninewells Hospital)H-Index: 17
Last. Adam T. HillH-Index: 43
view all 5 authors...
Summary Statins are widely used to lower cholesterol and prevent complications of cardiovascular disease. The non-lipid lowering (pleiotropic) effects of statins may also have applications to the management of infections. These include effects on endothelial function, inflammation and coagulation pathways. Several observational studies have shown a significant reduction in 30-day mortality associated with prior statin therapy in hospitalised patients with sepsis and community acquired pneumonia....
56 CitationsSource
#1Imad M. TleyjehH-Index: 38
#2Tarek KashourH-Index: 16
Last. Talal IbrahimH-Index: 6
view all 7 authors...
Background Emerging epidemiological evidence suggests that statin use may reduce the risk of infections and infection-related complications. Our objective was to examine the association between statin use and the risk of infections and related outcomes. Methods We searched several electronic databases from inception through December 2007 for randomized trials and cohort studies that examined the association between statin use and the risk or outcome of infections. Data on study characteristics, ...
188 CitationsSource
#1Peter S. SeverH-Index: 72
#2Neil Poulter (Imperial College London)H-Index: 74
Last. Jan ÖstergrenH-Index: 48
view all 14 authors...
Aims To determine the cardiovascular benefits in those originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial—2.2 years after closure of the lipid-lowering arm of the trial (ASCOT-LLA). Methods and results The Blood Pressure Lowering Arm of the ASCOT trial (ASCOT-BPLA) compared two different antihypertensive treatment strategies on cardiovascular outcomes. ASCOT-LLA was a double-blind placebo-controlled trial of atorvastatin in those enrolled into ASCOT-BPLA with total...
83 CitationsSource
#1Ian Ford (UCD: University College Dublin)H-Index: 113
#2Heather Murray (UCD: University College Dublin)H-Index: 31
Last. Stuart M. CobbeH-Index: 60
view all 6 authors...
Background The West of Scotland Coronary Prevention Study was a randomized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infarction, with an average follow-up of approximately 5 years. The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infarction was reduced from 7.9 to 5.5% (P<0.001) in the treatment group. Extended follow-up data were obtained for approximately 10 years...
341 CitationsSource
#1James K. Liao (Brigham and Women's Hospital)H-Index: 93
Statins are potent inhibitors of cholesterol biosynthesis and exert beneficial effects in the primary and secondary prevention of coronary artery disease. However, the overall benefits observed with statins appear to occur much earlier and to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or “pleiotropic” effects of statins involve improving endothe...
223 CitationsSource
#1Björn Dahlöf (Sahlgrenska University Hospital)H-Index: 87
#2Peter S. Sever (Imperial College London)H-Index: 72
Last. Jan ÖstergrenH-Index: 48
view all 14 authors...
Summary Background The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and β blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics and β blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril...
2,258 CitationsSource
Cited By81
Newest
#1Manel Mata-Cases (Adria Airways)H-Index: 13
#2Josep Franch-Nadal (ISCIII: Carlos III Health Institute)H-Index: 15
Last. Didac Mauricio (Autonomous University of Barcelona)H-Index: 37
view all 4 authors...
In the context of type 2 diabetes, the definition of therapeutic inertia should include the failure not only to intensify therapy, but also to deintensify treatment when appropriate and should be distinguished from appropriate inaction in cases justified by particular circumstances. Therapy should be intensified when glycemic control deteriorates to prevent long periods of hyperglycemia, which increase the risk of complications. Strategic plans to overcome therapeutic inertia must include action...
Source
#1Nuno Sales Craveiro (UBI: University of Beira Interior)H-Index: 1
#2Bruno Silva LopesH-Index: 1
Last. Luís Costa Matos (UBI: University of Beira Interior)H-Index: 1
view all 7 authors...
INTRODUCTION: Statins are widely prescribed drugs with established efficacy in primary and secondary prevention of cardiovascular events. Although they are mostly well tolerated, several authors have been emphasizing that the statins' safety profile is not totally clarified especially when considering risk of cancer in patients with long-term exposure to statins. This meta-analysis was aimed at evaluating the risk of cancer in patients with prolonged exposure to statins. METHODS: Medline, Cochra...
1 CitationsSource
#1Matthew M.Y. Lee (Glas.: University of Glasgow)H-Index: 7
#2Naveed Sattar (Glas.: University of Glasgow)H-Index: 128
Last. Chris J. Packard (Glas.: University of Glasgow)H-Index: 94
view all 4 authors...
Purpose of Review We summarize the best evidence for statins in the prevention and treatment of heart failure.
2 CitationsSource
#1Keshav Kumar GuptaH-Index: 1
#2Shair Ali (St George's Hospital)H-Index: 1
Last. Ranjodh Singh SangheraH-Index: 1
view all 3 authors...
Coronary heart disease (CHD) is the leading cause of mortality worldwide and high low-density lipoprotein (LDL) cholesterol levels have been shown to be key in the pathogenesis of this condition. Lipid control has therefore been the subject of decades of research and has led to many large and robust randomized controlled trials, as well as the highest grossing drug of all time—Lipitor (atorvastatin). Statin therapy has long been indicated for secondary and more recently primary prevention. Howev...
2 CitationsSource
#1Xiaoling Cai (PKU: Peking University)H-Index: 11
#2Dayi Hu (PKU: Peking University)H-Index: 13
Last. Linong Ji (PKU: Peking University)H-Index: 34
view all 13 authors...
Nationwide data on glycemic control, blood pressure (BP) control and lipid control in patients with newly diagnosed type 2 diabetes were vacant in China. The aim of this study was to assess the clinical outcomes for these patients. This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes less than 6 months were enrolled. Hemoglobin A1c (HbA1c) levels, BP levels and lipid levels were collected at baseline and the follow-ups. This ...
Source
#1Wen-Han FengH-Index: 1
#2Chun-Yuan ChuH-Index: 10
Last. Sheng-Hsiung SheuH-Index: 20
view all 10 authors...
BACKGROUND: Secondary prevention therapy for patients with coronary artery disease using an antiplatelet agent, β-blocker, renin-angiotensin system blocker (RASB), or statin plays an important role in the reduction of coronary events after coronary artery bypass grafting (CABG) surgery or percutaneous coronary intervention (PCI). We analyzed the status and effects of secondary prevention after coronary revascularization in Taiwan. METHODS: This national population-based cohort study was conducte...
Source
#1Kyu Hong Kim (Yonsei University)H-Index: 6
#2Chan Joo Lee (Yonsei University)H-Index: 14
Last. Hye Sun Lee (Yonsei University)H-Index: 49
view all 15 authors...
Abstract Background and aims Limited data is available on the benefit of statin for primary prevention in the elderly. The aim of this study is to investigate whether statin for primary prevention is effective in lowering the cardiovascular risk and all-cause death in individuals aged >75 years. Methods This was a retrospective, propensity score-matched study and data were acquired between 2005 and 2016 in a tertiary university hospital. Of the 6414 patients screened, 1559 statin-naive patients ...
2 CitationsSource
#1Johanna L. Johnson (Duke University)H-Index: 16
#2Cris A. Slentz (Duke University)H-Index: 36
Last. William E. Kraus (Duke University)H-Index: 81
view all 5 authors...
Background: STRRIDE (Studies Targeting Risk Reduction Interventions through Defined Exercise) was an eight-month exercise study conducted from 1998-2003. Subjects were randomized to control or one of three exercise groups differing in intensity and amount. To determine if there were legacy effects, we invited 161 individuals who completed the intervention phase to return for a 10-year Reunion study. Methods: Subjects completed medical history and physical activity questionnaires. Height, body we...
3 CitationsSource
#1Anne Langsted (Copenhagen University Hospital)H-Index: 18
#2Børge G. Nordestgaard (UCPH: University of Copenhagen)H-Index: 125
Summary Before 2009 essentially all societies, guidelines, and statements required fasting before measuring a lipid profile for cardiovascular risk prediction. This was mainly due to the increase seen in triglycerides during a fat tolerance test. However, individuals eat much less fat during a normal day and nonfasting triglycerides have been shown to be superior to fasting in predicting cardiovascular risk. Lipids and lipoproteins only change minimally in response to normal food intake: in four...
3 CitationsSource
#1Chau L B Ho (UTAS: University of Tasmania)
#2Enayet K. Chowdhury (Monash University)H-Index: 12
Last. Malcolm J. WestH-Index: 39
view all 16 authors...
BACKGROUND: There is currently insufficient evidence to support the use of lipid-lowering drug treatment (LLT) for primary prevention of cardiovascular disease (CVD) in the elderly.OBJECTIVES: We examined the relationship of early initiation of LLT with short- and long-term allcause and CVD mortality in persons older than 65 years in this post hoc study from the Second Australian National Blood Pressure study (ANBP2).METHODS: This was an in- and post-trial observational study. About 4257 hyperte...
Source