With statins reduce risk of coronary events even if already at low risk

reposted from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60367-5/abstract
pdf http://download.thelancet.com/pdfs/journals/lancet/PIIS0140673612603675.pdf?id=3d35b1b5aa0ec416:58d1b5c9:13bdbd3b67c:5911356606963137

crabsallover highlights, key points, comments / links.

The Lancet, Volume 380, Issue 9841, Pages 581 - 590, 11 August 2012

>

doi:10.1016/S0140-6736(12)60367-5

Published Online: 17 May 2012

The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials

Cholesterol Treatment Trialists' (CTT) Collaborators 
Summary

Background

Statins reduce LDL cholesterol and prevent vascular events, but their net effects in people at low risk of vascular events remain uncertain.

Methods

This meta-analysis included individual participant data from 22 trials of statin versus control (n=134 537; mean LDL cholesterol difference 1·08 mmol/L; median follow-up 4·8 years) and five trials of more versus less statin (n=39 612; difference 0·51 mmol/L; 5·1 years). Major vascular events were major coronary events (ie, non-fatal myocardial infarction or coronary death), strokes, or coronary revascularisations. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy (no statin or low-intensity statin) (<5%, ≥5% to <10%, ≥10% to <20%, ≥20% to <30%, ≥30%); in each, the rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated.

Findings

Reduction of LDL cholesterol with a statin reduced the risk of major vascular events (RR 0·79, 95% CI 0·77—0·81, per 1·0 mmol/L reduction), largely irrespective of age, sex, baseline LDL cholesterol or previous vascular disease, and of vascular and all-cause mortality. The proportional reduction in major vascular events was at least as big in the two lowest risk categories as in the higher risk categories (RR per 1·0 mmol/L reduction from lowest to highest risk: 0·62 [99% CI 0·47—0·81], 0·69 [99% CI 0·60—0·79], 0·79 [99% CI 0·74—0·85], 0·81 [99% CI 0·77—0·86], and 0·79 [99% CI 0·74—0·84]; trend p=0·04), which reflected significant reductions in these two lowest risk categories in major coronary events (RR 0·57, 99% CI 0·36—0·89, p=0·0012, and 0·61, 99% CI 0·50—0·74, p<0·0001) and in coronary revascularisations (RR 0·52, 99% CI 0·35—0·75, and 0·63, 99% CI 0·51—0·79; both p<0·0001). For stroke, the reduction in risk in participants with 5-year risk of major vascular events lower than 10% (RR per 1·0 mmol/L LDL cholesterol reduction 0·76, 99% CI 0·61—0·95, p=0·0012) was also similar to that seen in higher risk categories (trend p=0·3). In participants without a history of vascular disease, statins reduced the risks of vascular (RR per 1·0 mmol/L LDL cholesterol reduction 0·85, 95% CI 0·77—0·95) and all-cause mortality (RR 0·91, 95% CI 0·85—0·97), and the proportional reductions were similar by baseline risk. There was no evidence that reduction of LDL cholesterol with a statin increased cancer incidence (RR per 1·0 mmol/L LDL cholesterol reduction 1·00, 95% CI 0·96—1·04), cancer mortality (RR 0·99, 95% CI 0·93—1·06), or other non-vascular mortality.

Interpretation

In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered.

11 per 1000 over 5 years = 2.2 per 100 over 10 years, for 1mmol/L reduction in LDL cholesterol. My risk would reduce from 8 to 6 per 100 over 10 years or from 4% to 3% over 5 years if I take statins and reduce LDL cholesterol from 3.1 (3/1/13 result) to 2.1mmol/L.

Funding

British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.

NICE guidelines on Lipid Management & Statins being updated

reposted from: http://guidance.nice.org.uk/CG/WaveR/123

crabsallover highlights, key points, comments / links.

Following on from the CTT 2012 report, NICE are investigating new guidelines for use of statins for people with a <=10% risk of heart attack or stroke in next 10 years.

NICE guidelines on lipid management and use of Statins are being updated. See the scope and 2nd meeting (October 2012) minutes.

The risk assessment stage of the NHS Health Check (formerly known as the Vascular Check Programme) uses a risk engine for people aged 40–74 years to calculate their 10-year risk of CVD. Blood lipids, including cholesterol, are a modifiable risk factor for CVD. The risk of CVD is directly related to blood cholesterol levels and it is estimated that more than 50% of CVD in developed countries is a result of blood cholesterol levels higher than 3.8 mmol/litre. Blood cholesterol and other lipid components can be modified by drugs, physical activity and dietary changes; a multifactorial approach is likely to yield most benefit. (pg 2 of scope)

Key clinical issues that will be covered a) The most appropriate risk tool system to estimate a person’s absolute risk of developing CVD for: people without diabetes – for example, age alone, QRISK and Framingham risk assessment tools (10-year or lifetime risk)

Lipid modification strategy: for example, fixed dose or treating to a target lipid level.

c) Pharmacological interventions
(1) to reduce the risk of developing CVD (primary prevention) and (2) for secondary prevention in people with established CVD:
First-line treatment: statins.
Second-line treatment (alone or in combination with statins):
fibrates, anion-exchange resins, nicotinic acid group, omega-3 fatty acids.

5.1.1 NICE guidance to be updated
This guideline will update and replace the following NICE guidance:
Lipid modification. NICE clinical guideline 67 (2008).
Statins for the prevention of cardiovascular events. NICE technology appraisal guidance 94 (2006).

Statins—should we adjust the risk:benefit ratio?

reposted from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60111-6/fulltext?rss=yes

crabsallover highlights, key points, comments / links.

The Lancet

The prevailing opinion that statins are an elixir for long life was challenged with the recent publication of the Cochrane review, Statins for the primary prevention of cardiovascular disease. After analysing 16 trial arms with 34 272 participants, the authors found no evidence of harm, and mortality, composite cardiovascular endpoints, and revascularisations were reduced. But they concluded: “caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.”

The conclusion seems at odds with the findings. However, the authors found the evidence of insufficient quality to allow them to conclude differently; many trials included patients with a previous cardiovascular event, and the authors state that poor reporting of adverse events and selective reporting of outcomes contributed to their failure to draw a positive conclusion. They state that the evidence is “impossible to disentangle without individual patient data”.

The authors' conclusion is also at odds with the recent Cholesterol Treatment Trialists' (CTT) Collaboration meta-analysis, published in The Lancet. Individual patient data from around 70 000 patients with no previous cardiovascular disease were analysed, and showed that statins significantly reduced the relative risk of a cardiovascular event by 0·75 per 1 mmol fall in LDL cholesterol.

Unfortunately, the media are quick to forget, and have reported the Cochrane's headline-grabbing details with scant regard for the preceding evidence. This approach will have left many patients at best bewildered. The media have also largely ignored the Cochrane authors' conclusion that the results support guidelines from the UK's National Institute of Health and Clinical Excellence, which recommends statins are considered for primary prevention in patients with an annual incidence of cardiovascular events of over 2%.

So what should general practitioners (GPs), who are faced with increasing numbers of low-risk patients worried about mildly raised cholesterol, do? The Cochrane review has muddied the water, but the available evidence shows that statins are safe, and evidence from the CTT Collaboration also shows that reductions in cholesterol per se can produce benefits. So, the simple answer is that GPs should do what they always have done—clearly explain the risks and benefits to patients so that the patient is able to choose the strategy that is best for them.

Cholesterol Treatment Trialists' Collaboration (CTT) 170,000 patients in various trials (second cycle)

crabsallover highlights, key points, comments / links.
reposted from:  http://www.ctsu.ox.ac.uk/projects/ctt
I've already blogged the second cycle CCT trial here and in the last few days here. 

Cholesterol Treatment Trialists' Collaboration (CTT)

170,000 patients in various trials (second cycle)

First cycle

Second cycle

Publications

Funders

Objectives

The Cholesterol Treatment Trialists' (CTT) Collaboration was established in 1994 after it was identified that no single ongoing trial would have sufficient statistical power to address some key uncertainties about the effects of lowering cholesterol. It was recognised that, while the individual trials might be large enough to demonstrate effects on the aggregate of all coronary events, they might well over- or underestimate any effects on coronary death or on other specific vascular or non-vascular outcomes, especially when particular subgroups of participants were considered. Hence, it was planned to conduct periodic meta-analyses of individual participant data on mortality and morbidity from all relevant large-scale randomised trials of lipid-modifying treatments whose first results would appear subsequently (see published protocol¹).

First Cycle

Results

The first cycle of analyses included 14 randomised trials of statin therapy, and involved over 8000 deaths, 14,000 major vascular events, and 5000 cancers among 90,056 participants². The mean duration of treatment in these trials was about 5 years, and the overall average difference in LDL cholesterol at 1 year was 1·09 mmol/l. All analyses were weighted by the absolute difference in LDL cholesterol in each trial after 1 year of treatment. Overall, there was a 12% reduction in all-cause mortality per mmol/l LDL cholesterol reduction, attributable mainly to a proportional reduction of about one fifth in CHD deaths per mmol/l lower LDL cholesterol (figure). Among the non-vascular causes of death, there was no evidence that lowering LDL cholesterol with a statin adversely influenced the risk of death from cancer, respiratory disease, trauma, or other/unknown causes.

There was a significant trend towards greater proportional reductions in major vascular events being associated with greater LDL cholesterol reductions in the different trials (figure), but no heterogeneity among the results of the individual trials after adjusting for achieved differences in LDL cholesterol. Overall, there was a one fifth proportional reduction in the incidence of major vascular events per mmol/l LDL cholesterol reduction, reflecting similar proportional reductions of about one fifth in major coronary events, coronary revascularisation procedures, and strokes (figure). The one fifth reduction in stroke was mainly attributable to a reduction in ischaemic stroke, whilst there was no evidence of an adverse effect on haemorrhagic stroke (relative risk [RR] 1.05 [99% CI 0.78-1.41]; p=NS).

Given the large numbers of major vascular events, the effects of lowering LDL cholesterol with a statin could be examined particularly reliably in various different circumstances (e.g. sex, age, treated for hypertension, history of diabetes, LDL cholesterol).

The incidence of major vascular events was reduced by about one fifth per mmol/l LDL cholesterol reduction in each pre-specified subgroup, and was statistically significant in each of these subgroups considered separately (figure, figure cont.). There were also significant reductions in the incidence of major vascular events in a number of other subgroups of interest (including people with pre-treatment LDL cholesterol ≤2·6 mmol/l, diabetic individuals without pre-existing vascular disease, women and people aged over 75 years).

There was a significant 10% proportional reduction in major vascular events during the first year after randomisation, which was followed by highly significant annual reductions of around one-quarter during each subsequent year (figure).

There was no evidence that lowering LDL cholesterol with statin therapy increased the risk of developing cancer, nor was there any evidence of an excess incidence of cancer emerging with increasing duration of treatment (figure). Moreover, when cancer was analysed by site, there were no apparent excesses for any particular site-specific cancer (figure).

Benefits of statin therapy among patients with diabetes mellitus

The CTT collaboration explored the effects of statin therapy in more detail among the 18,686 individuals with diabetes (1466 type 1 and 17,220 type 2) included within the 14 trials³. During mean follow up of 4.3 years, 3247 of these diabetic individuals had major vascular events. Among them, there was a 9% proportional reduction in all-cause mortality per mmol/l reduction in LDL cholesterol, which was similar to the 13% reduction among those without diabetes (figure). This reflected a significant reduction in vascular mortality, but no apparent effect on non-vascular mortality (or on cancer incidence). There was a one fifth proportional reduction in major vascular events per mmol/l reduction in LDL cholesterol among people with diabetes, which again was similar to the effect observed in those without diabetes (figure). Among diabetic participants there were also separately significant reductions of about one fifth in myocardial infarction or coronary death, in coronary revascularisation, and in stroke. The reduction in major vascular events was similar among diabetic participants with pre-existing vascular disease and those with no such history (figure). Among diabetic individuals, there was no evidence that the relative effects of statin therapy differed by diabetes type (type 1 or 2), gender, age, systolic or diastolic blood pressure, smoking, body mass index, renal function, predicted annual risk of a major vascular event, (figure, figure cont.) or the baseline lipid profile (figure). The effects on major vascular events started to emerge within the first year, but were greater in subsequent years (figure). Consequently, these new analyses suggest that statin therapy should be considered routinely in all people with diabetes, unless there are particular reasons not to do so (e.g. pregnancy or a low absolute risk of vascular disease in a young adult with type I diabetes).

Publications

• Cholesterol Treatment Trialists' (CTT) Collaborators
  Protocol for a prospective collaborative overview of all current and planned randomized trials of cholesterol treatment regimens
  Am J Cardiol 1995; 75(16):1130-4
• Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R, Cholesterol Treatment Trialists' (CTT) Collaborators
  Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins
  Lancet 2005; 366(9493):1267-78
  • Slides: view^* or download
• Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Baigent C, Cholesterol Treatment Trialists' (CTT) Collaborators:
  Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis
  Lancet 2008; 371(9607):117–25
  • Slides: view^* or download

Main publications from trials included in the first cycle

• AFCAPS/TEXCAPS (AirForce/Texas Coronary Atherosclerosis Prevention Study)
• ALERT (Assessment of Lescol in Transplantation)
• ALLHAT-LLT (Antihypertensive Lipid Lowering Heart Attack Trial)
• ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial)
• CARDS (Collaborative Atorvastatin Diabetes Study)
• CARE (Cholesterol and Recurrent Events Study)
• GISSI Prevention (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico):
• HPS (Heart Protection Study)
• LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease)
• LIPS (Lescol Intervention Prevention Study)
• Post-CABG (Post-Coronary Artery Bypass Graft study)
• PROSPER (Prospective Study of Pravastatin in the Elderly at Risk)
• 4S (Scandinavian Simvastatin Survival Study)
• WOSCOPS (West of Scotland Coronary Prevention Study)

Second Cycle

The main purpose of the second cycle was to assess the effects of additional reductions in LDL cholesterol among patients receiving a standard statinregimen, but the meta-analyses of trials comparing statin versus control have also been updated.

Background

Comparisons of more versus less intensive regimens: The first cycle indicated that there was an approximately linear relationship between the absolute reductions in LDL cholesterol and the proportional reductions in major vascular events. However, a direct test of the hypothesis that further reductions in LDL-cholesterol would provide additional reduction in risk requires randomised trials of a more intensive versus less intensive LDL-lowering regimen. To date, five large trials have examined this hypothesis: two have been conducted among patients with a recent acute coronary syndrome (PROVE-IT [Pravastatin or Atorvastatin Evaluation and Infection Therapy]⁵ and A to Z⁶) and three among patients with aprior MI (TNT [Treating to New Targets]⁷, IDEAL [Incremental Decrease inEndpoints Through Aggressive Lipid Lowering]⁸ and SEARCH [Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine]⁹) (figure).

Extended comparisons of statin versus control: The first cycle included 14 trials comparing a statin versus a control regimen. In this updated analysis the additional trials are: ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events)¹⁰; 4D (Die Deutsche Diabetes Dialyze)¹¹; ASPEN (Atorvastatin Study for Prevention of coronary heart disease Endpoints in non-insulin dependent diabetes mellitus)¹²; MEGA (Management of Elevated cholesterol in the primary prevention group of Adult Japanese)¹³; JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)¹⁴; GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza cardiaca)¹⁵ and AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events)¹⁶ (figure).

Results

The second cycle of analyses included 26 randomised trials of statin therapy: 5 trials were of more vs. less statin therapy (39,612 patients, median follow up 5.1 years) and 21 trials were of statin vs. control (129,526 patients, median follow up 4.8 years). Taken together, these trials involved 15,969 deaths, 24,323 major vascular events, and 10,124 cancers among 169,138 participants⁴. The average difference in LDL cholesterol at 1 year among the statin vs. control trials was 1.07 mmol/L, whilst in the trials of more versus less intensive statin therapy the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Analyses were done both before and after weighting for the absolute difference in LDL cholesterol in each trial after 1 year of treatment.

Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events (figure), consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; 

p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005) (figure). Overall the weighted average further reduction in major vascular events was 28% (22-34; p<0.0001) per mmol/L reduction in LDL-cholesterol (figure) 

with separately significant reductions in each of the major components of this composite outcome (figure).

The results of the updated meta-analysis of the 21 statin vs. control trials were similar to those observed in the first cycle: there was a highly significant 21% (95% CI 19-23;p<0.0001) reduction per mmol/L LDL cholesterol reduction. The proportional reductions per mmol/L LDL cholesterol reduction were separately significant for coronary death or non-fatal myocardial infarction (24%, 95% CI 21–27;p<0·0001), coronary revascularisation (24%, 95% CI 20–27; p<0·0001), and ischaemic stroke (20%, 95% CI 14–26; p<0·0001) (figure).

When both types of trial were combined, similar proportional reductions in major vascular events per mmol/L LDL cholesterol reduction were found in all types of patient studied (figure, figure cont.) 

(rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen (figure).

Across all 26 trials, all-cause mortality was reduced by 10% per mmol/L LDL reduction (RR 0·90, 95% CI 0·87–0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74–0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81–0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84–1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81–1·18; p=0·8) (figure). 

No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92–1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96–1·04; p=0·9) (figure), even at low LDL cholesterol concentrations.

Publication

• Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R, Cholesterol Treatment Trialists’ (CTT) Collaboration
  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trialsLancet 2010; 376: 1670–81
• Slides: view* or download

Main publications from additional trials in the second cycle

• A to Z (Aggrastat to Zocor)
• IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering)
• PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy)
• SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine)
• TNT (Treating to New Targets)
• ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events)
• ASPEN (Atorvastatin Study for Prevention of Coronary Heart Disease Endpointsin Non-Insulin-Dependent Diabetes Mellitus)
• AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events)
• 4D (Die Deutsche Dialyse Studie)
• GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza cardiaca)
• JUPITER (Justification for the Use of Statins in Prevention: an InterventionTrial Evaluating Rosuvastatin)
• MEGA (Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese)

References

1. Cholesterol Treatment Trialists' (CTT) Collaborators. Protocol for a prospective collaborative overview of all current and planned randomized trials of cholesterol treatment regimens. Am J Cardiol 1995; 75(16):1130-4.
2. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R, Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366(9493):1267-78.
3. Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Baigent C, Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008; 371(9607): 117–25.
4. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R, Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet 2010; 376: 1670–81.
5. Cannon CP, Braunwald E, McCabe CH et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350:1495-504.
6. de Lemos JA, Blazing MA, Wiviott SD et al . Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292: 1307-16.
7. La Rosa JC, Grundy SM, Waters DD, et al. Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease. N Engl J Med 2005; 352:1425-1435.
8. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005; 294: 2437-45.
9. Armitage J, Bowman L, Wallendszus K, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 2010; 376: 1658–69.
10. Koren M, Hunninghake D, ALLIANCE Investigators. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: The ALLIANCE study. J Am Coll Cardiol 2004; 44: 1772-79.
11. Wanner C, Krane V, März W, et al. for the German Diabetes and Dialysis Study Group. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353: 238-48.
12. Knopp RH, d'Emden M, Smilde JG, et al. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006; 29: 1478-85.
13. Nakamura H, Arakawa K, Itakura H, et al. for the MEGA Study Group. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet 2006; 368: 1155-63.
14. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. N Engl J Med 2008;359:2195-207.
15. Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 1231–39.
16. Fellström, BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and Cardiovascular Events in Patients Undergoing Hemodialysis. N Engl J Med 2009;360:1395-407.

CTT Funders

UK

   

Australia