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C Baigent

Publications and source records attributed to C Baigent.

At least 19 recordsLinked to original sources
PubMed2005

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.

BACKGROUND: 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. METHODS: A prospective meta-analysis of data from 90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol. FINDINGS: During a mean of 5 years, there were 8186 deaths, 14,348 individuals had major vascular events, and 5103 developed cancer. Mean LDL cholesterol differences at 1 year ranged from 0.35 mmol/L to 1.77 mmol/L (mean 1.09) in these trials. There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0.88, 95% CI 0.84-0.91; p<0.0001). This reflected a 19% reduction in coronary mortality (0.81, 0.76-0.85; p<0.0001), and non-significant reductions in non-coronary vascular mortality (0.93, 0.83-1.03; p=0.2) and non-vascular mortality (0.95, 0.90-1.01; p=0.1). There were corresponding reductions in myocardial infarction or coronary death (0.77, 0.74-0.80; p<0.0001), in the need for coronary revascularisation (0.76, 0.73-0.80; p<0.0001), in fatal or non-fatal stroke (0.83, 0.78-0.88; p<0.0001), and, combining these, of 21% in any such major vascular event (0.79, 0.77-0.81; p<0.0001). The proportional reduction in major vascular events differed significantly (p<0.0001) according to the absolute reduction in LDL cholesterol achieved, but not otherwise. These benefits were significant within the first year, but were greater in subsequent years. Taking all years together, the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 (95% CI 39-57) fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 (19-31) per 1000 among participants with no such history. There was no evidence that statins increased the incidence of cancer overall (1.00, 0.95-1.06; p=0.9) or at any particular site. INTERPRETATION: Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individual's absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event.

Cause of Death↗
PubMed2005

Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis.

OBJECTIVES: To assess the benefits in terms of reductions in the risks of deep vein thrombosis (DVT) and of pulmonary embolism (PE), and hazards in terms of major bleeding, of: (i) mechanical compression; (ii) oral anticoagulants; (iii) dextran; and (iv) regional anaesthesia (as an alternative to general anaesthesia) in surgical and medical patients. DATA SOURCES: Electronic databases, search of Antithrombotic Trialists' Collaboration database, contact with trialists and manufacturers. REVIEW METHODS: All trials identified as fitting the selection criteria were independently assessed. The primary outcomes were DVT, PE and major bleeding events, and proximal venous thrombosis (PVT) and fatal PE were secondary outcomes. Trials were subdivided into those that had assessed a method as the only means of thromboprophylaxis ('monotherapy') and those that had assessed the effects of adding a method to another form of thromboprophylaxis ('adjunctive therapy'). RESULTS: Mechanical compression methods reduced the risk of DVT by about two-thirds when used as monotherapy and by about half when added to a pharmacological method. These benefits were similar irrespective of the particular method used (graduated compression stockings, intermittent pneumatic compression or footpumps) and were similar in each of the surgical groups studied. Mechanical methods reduced the risk of PVT by about half and the risk of PE by two-fifths. Oral anticoagulants, when used as monotherapy, reduced the risk of DVT and of PVT by about half, and this protective effect appeared similar in each of the surgical groups studied. There was an apparently large four-fifths reduction in the role of PE, but not only was the magnitude of this reduction statistically uncertain, but also pulmonary embolism was reported by a minority of trials, so it may be subject to selection bias. Oral anticoagulant regimens approximately doubled the risk of major bleeding and appeared less effective at preventing DVT than heparin regimens, although were associated with less major bleeding. Dextran reduced the risk of DVT and of PVT by about half, again irrespective of the type of surgery, but too few studies had reported PE to provide reliable estimates of effect on this outcome. Dextran appeared to be less effective at preventing DVT than the heparin regimens studied. Dextran was associated with an increased risk of bleeding, but too few bleeds had occurred for the size of this excess risk to be estimated reliably. Compared with general anaesthesia, regional anaesthesia reduced the risk of DVT by about half, and this benefit appeared similar in each of the surgical settings studied. Regional anaesthesia was associated with less major bleeding than general anaesthesia. CONCLUSIONS: In the absence of a clear contraindication (such as severe peripheral arterial disease), patients undergoing a surgical procedure would be expected to derive net benefit from a mechanical compression method of thromboprophylaxis (such as graduated compression stockings), irrespective of their absolute risk of venous thromboembolism. Patients who are considered to be at particularly high risk of venous thromboembolism may also benefit from a pharmacological thromboprophylactic agent, but since oral anticoagulant and dextran regimens appear less effective at preventing DVT than standard low-dose unfractionated heparin or low molecular weight heparin regimens, they may be less suitable for patients at high risk of venous thromboembolism, even though they are associated with less bleeding. Whenever feasible, the use of regional anaesthesia as an alternative to general anaesthesia may also provide additional protection against venous thromboembolism. There is little information on the prevention of venous thromboembolism among high-risk medical patients (such as those with stroke), so further randomised trials in this area would be helpful.

Administration, Oral↗
PubMed2001

Epidemiological evaluation of known and suspected cardiovascular risk factors in chronic renal impairment.

Patients with chronic renal impairment (CRI) are at greatly increased risk for premature vascular disease; however, little is known about its evolution. This paper describes a cohort of patients with CRI and reports study design, baseline demographic and biochemical data, and comparisons with two contemporaneous age- and sex-matched control groups, one with established coronary artery disease and the other without overt vascular disease. Among 369 individuals (median age, 63 years; range, 18 to 88 years; 67% men) with CRI, 34% had a history of vascular disease and 21% had electrocardiographic left ventricular hypertrophy (LVH). Even in those with mild renal impairment (serum creatinine < 2.1 mg/dL), approximately one third had vascular disease and 12% had LVH. A history of hypertension was present in 76% of the CRI group, but as compared with controls, systolic and diastolic blood pressures were not elevated. Low-density lipoprotein (LDL) cholesterol concentration also was not elevated, but CRI was associated with elevated serum triglyceride and plasma homocysteine levels and reduced high-density lipoprotein (HDL) cholesterol, hemoglobin, and serum albumin concentrations. Across the spectrum of CRI, more severe renal dysfunction was associated with lower levels of diastolic blood pressure, LDL and HDL cholesterol, albumin, and hemoglobin, but increased levels of plasma homocysteine. This cross-sectional analysis shows that vascular disease is common in individuals with mild CRI attending a nephrology program and also suggests trends in the levels of a number of potential vascular risk factors with respect to severity of renal dysfunction. These results will be further quantified in a prospective biennial follow-up.

Adolescent↗
PubMed2000

Premature cardiovascular disease in chronic renal failure.

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.

Acute-Phase Proteins↗
PubMed2000

Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group.

OBJECTIVES: We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA). BACKGROUND: Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI. METHODS: This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0-36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial). RESULTS: Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use. CONCLUSIONS: Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.

Aged↗
PubMed1998

ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group.

OBJECTIVE: To assess effects of intravenous streptokinase, one month of oral aspirin, or both, on long term survival after suspected acute myocardial infarction. DESIGN: Randomised, "2 x 2 factorial," placebo controlled trial. SETTING: 417 hospitals in 16 countries. SUBJECTS: 17 187 patients with suspected acute myocardial infarction randomised between March 1985 and December 1987. Follow up of vital status complete to at least 1 January 1990 for 95% of all patients and to mid-1997 for the 6213 patients in United Kingdom. INTERVENTIONS: Intravenous streptokinase (1.5 MU in 1 hour) and oral aspirin (162 mg daily for 1 month) versus matching placebos. MAIN OUTCOME MEASURES: Mortality from all causes during up to 10 years' follow up, with subgroup analyses based on 4 year follow up. RESULTS: After randomisation, 1841 deaths were recorded in days 0-35, 991 from day 36 to end of year 1, 1478 in years 2-4, and 1230 in years 5-10. Allocation to streptokinase was associated with 29 (95% confidence interval 20 to 38) fewer deaths per 1000 patients during days 0-35. This early benefit persisted (death rate ratio 0.98 (0.92 to 1.04) for additional deaths between day 36 and end of year 10), so that there were 28 (14 to 42) and 23 (2 to 44) fewer deaths per 1000 patients treated with streptokinase after 4 years and 10 years respectively. There was no evidence that absolute survival benefit increased with prolonged follow up among any category of patient, including those presenting early after symptoms started or with anterior ST elevation. Nor did the early benefits seem to be lost in any category (including those aged over 70). Allocation to one month of aspirin was associated with 26 (16 to 35) fewer deaths per 1000 during first 35 days, with little further benefit or loss during subsequent years (death rate ratio 0.99 (0.93 to 1.06) between day 36 and end of year 10). The early benefit obtained with combination of streptokinase and one month of aspirin also seemed to persist long term. CONCLUSIONS: The early survival advantages produced by fibrinolytic therapy and one month of aspirin started in acute myocardial infarction seem to be maintained for at least 10 years.

Administration, Oral↗
PubMed1997

The need for large-scale randomized evidence.

The reliable detection of moderate differences in major health outcomes that arise as a result of treatment requires large-scale randomized evidence (and the appropriate interpretation of this evidence once it has been generated). This may take the form of a single mega-trial or, exceptionally, a meta-analysis of many smaller randomized trials may provide worthwhile information. Small or non-randomized studies cannot generally be trusted to distinguish reliably between a moderate benefit, a moderate hazard, and a negligible difference in major outcomes. Simple design, streamlined data collection, and use of the "uncertainty principle' to guide eligibility would all encourage the recruitment of larger samples in randomized trials. Future trials need to adopt these methods in order to detect any moderate improvements in major outcomes that may await discovery.

Clinical Trials, Phase III as Topic↗
PubMed1996

Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer reinfarctions per 1000 (2P = 0.04) and 1 (0.5) fewer pulmonary emboli per 1000 (2P = 0.01), but there was a small non-significant excess of stroke and a definite excess of 3 (1) major bleeds per 1000 (2P < 0.0001). CONCLUSIONS: The clinical evidence from randomised trials dose not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardial infarction (irrespective of whether any type of fibrinolytic therapy is used).

Anticoagulants↗