Research Area:	Clinical Epidemiology
Technology Exchange:	Medical statistics
Scientific Themes:	Clinical Trials & Epidemiology
Keywords:	Clinical trials, Meta-analysis, Epidemiology and Cardiovascular disease
Web Links:	CTSU website Podcast 'Lowering cholesterol in chronic kidney disease' Podcast 'Wider statin use saves lives'

Colin Baigent’s main research interest is the use of large-scale evidence, typically involving randomized trials and meta-analyses of those trials, for the prevention and treatment of cardiovascular disease. He coordinates two separate areas of research:

1. Large-scale collaborative meta-analyses of randomized trials: These very large projects generally involve detailed individual participant data from each trial, and the resulting analyses can provide reliable assessments of the benefits and risks of drug regimens for particular types of patients. They include the well-known Antithrombotic Trialists’ (ATT) and Cholesterol Treatment Trialists’ (CTT) Collaborations, which have helped establish the appropriate use of aspirin and statins in a wide range of people and conditions. More recently a new collaborative meta-analysis of trials has been completed that assesses the cardiovascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs and COX-2 inhibitors.
2. Cardiovascular complications of chronic kidney disease (CKD): Patients with chronic kidney disease are at substantially increased risk of cardiovascular disease, but the causes of such disease are unclear and there is little information available regarding its prevention. One major problem is that observational studies seeking to identify risk factors for cardiovascular disease are seriously distorted by the effects of renal disease on those risk factors (eg, CKD causes dyslipidaemia and hypertension). The most effective way of avoiding such bias is to randomize to treatments that modify disease risk factors, and Colin led the Study of Heart and Renal Protection (SHARP) among over 9000 kidney patients— the largest ever randomized trial in nephrology—which showed that lowering cholesterol reduces the risk of atherosclerotic vascular disease in CKD. His current research is utilising the extensive store of blood, urine and DNA from that trial in order to further explore the causes of cardiovascular disease in CKD.

Name	Department	Institution	Country
Prof Sir Rory E Collins	Clinical Trial Service Unit	Oxford University	UK
Carlo Patrono		University of Rome "La Sapienza"	Italy
Prof Sir Richard Peto FRS	Clinical Trial Service Unit	Oxford University	UK
David Wheeler		Royal Free Hospital	UK
Dr Martin J Landray	Clinical Trial Service Unit	Oxford University	UK

Cholesterol Treatment Trialists' (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C. 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. Lancet, 380 (9841), pp. 581-590. Read abstract | Read more

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

Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellström B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Grönhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R, SHARP Investigators et al. 2011. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet, 377 (9784), pp. 2181-2192. Read abstract | Read more

Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Hide abstract

Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R et al. 2010. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet, 376 (9753), pp. 1670-1681. Read abstract | Read more

Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy. Hide abstract

Antithrombotic Trialists' (ATT) Collaboration, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A et al. 2009. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet, 373 (9678), pp. 1849-1860. Read abstract | Read more

Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention. Hide abstract

Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R. 2008. Analyses of cancer data from three ezetimibe trials. N Engl J Med, 359 (13), pp. 1357-1366. Read abstract | Read more

Five years of statin therapy lowers low-density lipoprotein (LDL) cholesterol substantially and, over a 5-year period, results in reductions in the incidence of cardiovascular events. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial (ClinicalTrials.gov number, NCT00092677) has raised the hypothesis that adding ezetimibe to statin therapy for larger LDL cholesterol reductions might increase the incidence of cancer. Hide abstract

Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes J. 2008. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised controlled trials of statins (vol 366, pg 1267, 2005) LANCET, 371 (9630), pp. 2084-2084.

Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C. 2008. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet, 371 (9607), pp. 117-125. Read abstract | Read more

Although statin therapy reduces the risk of occlusive vascular events in people with diabetes mellitus, there is uncertainty about the effects on particular outcomes and whether such effects depend on the type of diabetes, lipid profile, or other factors. We undertook a prospective meta-analysis to help resolve these uncertainties. Hide abstract

Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. 2006. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ, 332 (7553), pp. 1302-1308. Read abstract | Read more

To assess the effects of selective cyclo-oxygenase-2 (COX 2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of vascular events. Hide abstract

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 et al. 2005. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet, 366 (9493), pp. 1267-1278. Read abstract | Read more

Results of previous randomised trials have shown that interventions that lower LDL cholesterol concentrations can significantly reduce the incidence of coronary heart disease (CHD) and other major vascular events in a wide range of individuals. But each separate trial has limited power to assess particular outcomes or particular categories of participant. Hide abstract

Baigent C, Landray M, Leaper C, Altmann P, Armitage J, Baxter A, Cairns HS, Collins R, Foley RN, Frighi V, Kourellias K, Ratcliffe PJ, Rogerson M, Scoble JE, Tomson CR, Warwick G, Wheeler DC et al. 2005. First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. Am J Kidney Dis, 45 (3), pp. 473-484. Read abstract | Read more

Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group. Hide abstract

Baigent C, Landry M. 2003. Study of Heart and Renal Protection (SHARP). Kidney Int Suppl, 63 (84), pp. S207-S210. Read abstract

Among patients with preexisting coronary heart disease, large-scale randomized trials have demonstrated that lowering low-density lipoprotein (LDL)-cholesterol concentration by about 1 mmol/L for 4-5 years reduces the risk of coronary events and strokes by about 25%. Patients with established chronic kidney disease (CKD) are at high risk of vascular disease, so the benefits of cholesterol-lowering therapy might be expected to be substantial in this population. Patients with CKD have generally been excluded from previous trials, however, and there is currently no reliable randomized evidence that lowering LDL-cholesterol would be beneficial among them. There are several reasons why the demonstrated benefits of lowering blood cholesterol in other populations might not translate to patients with CKD. First, observational studies among dialysis patients have reported a negative association between blood total cholesterol and mortality. Second, only about one quarter of cardiac mortality in such patients appears to be attributable to acute myocardial infarction, and potentially avoidable with cholesterol lowering, while the other common causes (e.g., cardiac arrest, arrhythmia, and heart failure) may not be as dependent on cholesterol levels. Finally, the long-term safety of cholesterol reduction among patients with CKD remains unclear. Hence, there is an important need for reliable direct evidence on whether lowering cholesterol prevents a worthwhile proportion of vascular events, without unacceptable toxicity, among patients with CKD. The Study of Heart and Renal Protection (SHARP) aims to assess the effects of cholesterol-lowering therapy with a combination of simvastatin and the cholesterol-absorption inhibitor ezetimide among around 9000 patients with CKD. Hide abstract

Antithrombotic Trialists' Collaboration. 2002. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ, 324 (7329), pp. 71-86. Read abstract

To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. Hide abstract

Baigent C, Burbury K, Wheeler D. 2000. Premature cardiovascular disease in chronic renal failure. Lancet, 356 (9224), pp. 147-152. Read abstract | Read more

There is a remarkable lack of reliable information about the determinants of risk of cardiovascular disease (CVD) among patients with chronic renal failure. Indeed, such patients have often been deliberately excluded from randomised trials of treatments of CVD, perhaps because of concerns about drug safety. But the absolute risk of CVD among them may be large, so the potential absolute benefits of treatments may also be large, and may well exceed any increased hazards. Hence, as well as further investigation of the underlying mechanisms of cardiac disease, it would be helpful to have some large-scale randomised trials in a wide range of renal patients of interventions (such as cholesterol-lowering drugs, antihypertensives, aspirin, B-vitamins, and antioxidant vitamins) that are of proven or suspected benefit in other settings. If safe and effective treatments can be identified, and started early in the natural history of renal failure, the exceptionally high risk of CVD experienced by these patients could be decreased before and after end-stage renal failure has occurred. Hide abstract

Peto R, Baigent C. 1998. Trials: the next 50 years. Large scale randomised evidence of moderate benefits. BMJ, 317 (7167), pp. 1170-1171.