PubMed Health⌕ Search

Biomedical subjects

Colin Baigent

Publications and source records attributed to Colin Baigent.

16 recordsLinked to original sources
PubMed2006

Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials.

OBJECTIVE: 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. DESIGN: Meta-analysis of published and unpublished tabular data from randomised trials, with indirect estimation of the effects of traditional NSAIDs. DATA SOURCES: Medline and Embase (January 1966 to April 2005); Food and Drug Administration records; and data on file from Novartis, Pfizer, and Merck. REVIEW METHODS: Eligible studies were randomised trials that included a comparison of a selective COX 2 inhibitor versus placebo or a selective COX 2 inhibitor versus a traditional NSAID, of at least four weeks' duration, with information on serious vascular events (defined as myocardial infarction, stroke, or vascular death). Individual investigators and manufacturers provided information on the number of patients randomised, numbers of vascular events, and the person time of follow-up for each randomised group. RESULTS: In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; P = 0.003), with no significant heterogeneity among the different selective COX 2 inhibitors. This was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; 1.86, 1.33 to 2.59; P = 0.0003), with little apparent difference in other vascular outcomes. Among trials of at least one year's duration (mean 2.7 years), the rate ratio for vascular events was 1.45 (1.12 to 1.89; P = 0.005). Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9%/year; 1.16, 0.97 to 1.38; P = 0.1). However, statistical heterogeneity (P = 0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (1.57, 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (0.88, 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac. CONCLUSIONS: Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD.

BACKGROUND: Evaluating the effects of decreasing low-density lipoprotein (LDL) cholesterol levels requires large randomized trials. In preparation for such a trial, we assessed the biochemical efficacy, safety, and tolerability of adding ezetimibe, 10 mg/d, to simvastatin, 20 mg/d, as initial therapy for such patients. METHODS: Two hundred three patients (152 predialysis patients with creatinine levels > or = 1.7 mg/dL [> or = 150 micromol/L], 18 patients on peritoneal dialysis therapy, and 33 patients on hemodialysis therapy) were randomly assigned to the administration of simvastatin, 20 mg/d, plus ezetimibe, 10 mg/d; or simvastatin, 20 mg, plus placebo ezetimibe daily. RESULTS: After 6 months, allocation to simvastatin monotherapy was associated with a 31-mg/dL (0.8-mmol/L) decrease in nonfasting LDL cholesterol levels compared with baseline. Allocation to simvastatin plus ezetimibe produced an additional 18-mg/dL (0.47-mmol/L) decrease in LDL cholesterol level, representing an incremental 21% reduction over that achieved with simvastatin monotherapy (P < 0.0001). There were no statistically significant effects of the addition of ezetimibe to simvastatin on triglyceride or high-density lipoprotein cholesterol levels. Ezetimibe was not associated with an excess risk of abnormal liver function test results or of elevated creatine kinase levels and did not impair absorption of fat-soluble vitamins. There were no serious adverse events caused by study treatment. CONCLUSION: This 6-month study shows that the addition of ezetimibe to simvastatin, 20 mg/d, as initial therapy for patients with chronic kidney disease was well tolerated and produced an additional 21% decrease in LDL cholesterol levels. The clinical efficacy and safety of combination therapy in this population are now being assessed in a large randomized trial.

Anticholesteremic Agents↗
PubMed2006

Statins: are any questions unanswered?

PURPOSE OF REVIEW: To summarize recent and ongoing randomized trials of statin therapy for the prevention of major vascular events. RECENT FINDINGS: Four large-scale randomized trials have compared high-dose vs. standard doses of statin therapy among patients with coronary heart disease, and their results suggest that higher doses are more effective for preventing major vascular events, albeit with evidence of increased toxicity. There is now clear evidence that statin therapy is effective among most patients with type 2 diabetes, although uncertainty remains about the benefits in those with advanced nephropathy. Ongoing trials will assess whether statin therapy is beneficial among patients with noncoronary vascular disease (such as congestive heart failure, cerebrovascular disease, or aortic stenosis), and among people with comorbid conditions or risk factors that increase the risk of vascular disease (including chronic kidney disease and raised C-reactive protein with below average low-density lipoprotein cholesterol). SUMMARY: Statin therapy safely reduces the risk of vascular events in a wide range of patients. Uncertainties persist about the effects of higher statin doses and the role of statins among patients with specific conditions or risk factors.

Cardiovascular Diseases↗
PubMed2005

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.

BACKGROUND: 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. METHODS: Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo. RESULTS: Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level > or = 1.7 mg/dL [> or =150 micromol/L], 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients [2%] versus placebo, 6 of 223 patients [3%]; P = not significant [NS]), although there was a 3-fold excess of minor bleeds (34 of 225 [15%] versus 12 of 223 patients [5%]; P = 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 [4%] versus 6 of 188 patients [3%]; P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients [34%] versus 56 of 188 patients [30%]; P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL [4.22 mmol/L] versus placebo, 196 mg/dL [5.08 mmol/L]; P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL [2.31 mmol/L] versus 114 mg/dL [2.96 mmol/L]; P < 0.0001), and triglyceride levels by 13% (166 mg/dL [1.87 mmol/L] versus 186 mg/dL [2.10 mmol/L]; P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase; P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels. CONCLUSION: During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events.

Adult↗
PubMed2004

Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study.

BACKGROUND: Studies in the general population suggest that low-grade inflammation, endothelial dysfunction, and platelet activation are associated with an increased risk of cardiovascular events. METHODS: Markers of inflammation, endothelial dysfunction, and platelet activation were measured in 334 patients with chronic kidney disease (serum creatinine >1.47 mg/dL [>130 micromol/L] at screening) and compared with 2 age- and sex-matched control groups, 1 comprising 92 patients with coronary artery disease and the other comprising 96 apparently healthy individuals with no history of cardiovascular or kidney disease. RESULTS: There was evidence of low-grade inflammation in the chronic renal impairment group compared with healthy controls, with higher concentrations of C-reactive protein (3.70 versus 2.18 mg/L, P < 0.01) and fibrinogen (3.48 versus 2.67 g/L, P < 0.001) and lower serum albumin concentration (41.8 versus 44.0 g/dL [418 versus 440 g/L], P < 0.001). More severe renal impairment was associated with a trend towards higher fibrinogen and lower albumin concentrations (both P < 0.001), although there was no association with higher C-reactive protein level. As compared to healthy controls, plasma von Willebrand factor (142 versus 108 IU/dL, P < 0.001) and soluble P-selectin concentrations (57.0 versus 43.3 ng/mL, P < 0.001) were also higher in the chronic renal impairment group. More severe renal impairment was associated with a trend towards higher levels of von Willebrand factor (P < 0.001) and of soluble P selectin (P < 0.05). CONCLUSION: This cross-sectional analysis demonstrates that chronic kidney disease is associated with low-grade inflammation, endothelial dysfunction, and platelet activation, even among patients with moderate renal impairment.

Adult↗
PubMed2004

Statin therapy in kidney disease populations: potential benefits beyond lipid lowering and the need for clinical trials.

PURPOSE OF REVIEW: This review outlines the limited information currently available on the effects of statins among patients with chronic kidney disease, and summarizes the ongoing randomized trials designed to address this question. RECENT FINDINGS: The effects of fluvastatin on major coronary events among renal transplant patients, and the effects of pravastatin and simvastatin in small subgroups of coronary patients with minor degrees of renal impairment, appear broadly compatible with those observed in trials conducted in non-renal populations. In addition, recent evidence from trials among patients with vascular disease or diabetes suggests that statin therapy may delay progressive loss of renal function. However, there remains substantial uncertainty regarding the effects of statin therapy among patients with established chronic kidney disease (pre-dialysis or dialysis patients). In particular, there does not appear to be a strongly positive relationship between blood cholesterol and cardiovascular events in such patients. This may be because uraemic cardiomyopathy and arteriosclerosis, which cause the majority of these events in chronic kidney disease patients, do not depend strongly on blood cholesterol. SUMMARY: Statins appear effective for the prevention of vascular events in people with established vascular disease and mild renal impairment, and may delay renal disease progression in such individuals. However, the effects of statins in patients with established chronic kidney disease are unknown, and we await the results of ongoing large-scale randomized trials of statin therapy among such patients.

Cardiovascular Diseases↗
PubMed2003

Study of Heart and Renal Protection (SHARP).

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.

Cholesterol, LDL↗
PubMed2003

Cholesterol and the risk of renal dysfunction in apparently healthy men.

Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as >/= 1.5 mg/dl (133 micromol/L), and reduced estimated creatinine clearance, defined as </=55 ml/min. Cholesterol parameters included total cholesterol (<200, 200 to 239, and >/= 240 mg/dl), HDL (<40 or >/= 40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval [CI], 1.10 to 2.86) for total cholesterol >/= 240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL <40 mg/dl, 2.34 (95% CI, 1.34 to 4.07) for the highest quartile of total cholesterol/HDL ratio (>/= >6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (>/= 196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine <1.5 mg/dl.

Cholesterol↗