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PubMed2001

Effects of quinapril on clinical outcome after coronary artery bypass grafting (The QUO VADIS Study). QUinapril on Vascular Ace and Determinants of Ischemia.

The QUO VADIS study was designed to explore whether 1 year of angiotensin-converting enzyme inhibition with quinapril (40 mg/day) would decrease ischemia in patients who underwent coronary artery bypass grafting (CABG). Patients (n = 149) scheduled for CABG were randomized 4 weeks before surgery. Study medication was used from randomization up to 1 year after CABG. Exercise testing was performed at randomization; the exercise test was repeated 1 year after CABG and patients underwent 48-hour Holter monitoring. Clinical ischemic events were recorded and defined as death, revascularization, myocardial infarction, recurrence of angina pectoris, ischemic stroke, or transient ischemic attack. Baseline characteristics were similar between groups. Total exercise time increased overall by 75 +/- 76 seconds 1 year after CABG (placebo +79 +/- 75 seconds, quinapril +72 +/- 79 seconds, p = 0.6). All patients had ischemic ST-segment changes at randomization; 33% of patients had ischemic ST-segment changes 1 year after CABG (placebo 29%, quinapril 37%, p = 0.4). On Holter monitoring, the number of patients experiencing > or = 1 episodes of ischemia was equal in both groups. Treatment with quinapril significantly reduced clinical ischemic events after CABG: 15% in patients on placebo versus 4% of patients on quinapril (hazard ratio 0.23, 95% confidence interval 0.06 to 0.87, p = 0.02). Long-term quinapril treatment significantly reduced clinical ischemic events within 1 year after CABG, although ischemia at exercise testing and Holter monitoring was unchanged.

Aftercare↗

PubMed2001

Development and validation of a clinical prediction rule for major adverse outcomes in coronary bypass grafting.

In this study, we develop and internally validate a clinical prediction rule for in-hospital major adverse outcomes, defined as death, renal failure, reinfarction, cardiac arrest, cerebrovascular accident, or coma, in patients who underwent coronary artery bypass grafting (CABG). All adult patients (n = 9,498) who underwent a CABG and no other concomitant surgery at 12 academic medical centers from August 1993 to October 1995 were included in the study. We assessed in-hospital major adverse outcomes and their predictors using information on admission, coronary angiography, and postoperative hospital course. Predictor variables were limited to information available before the procedure, and outcome variables were represented only by events that occurred postoperatively. We developed and internally validated a clinical prediction rule for any major adverse outcome after CABG. The rule's ability to discriminate outcomes and its calibration were assessed using receiver-operating characteristic analysis and the Hosmer-Lemeshow goodness-of-fit statistic, respectively. A major adverse outcome occurred in 6.5% of patients in the derivation set and 7.2% in the validation set. Death occurred in 2.5% of patients in the derivation set and 2.2% in the validation set. Sixteen variables were independently correlated with major adverse outcomes, with the risk score value attributed to each risk factor ranging from 2 to 12 points. The rule stratified patients into 6 levels of risk based on the total risk score. The spread in probability between the lowest and highest risk groups of having a major adverse outcome was 1.7% to 32.3% in the derivation set and 2.2% to 22.3% in the validation set. The prediction model performed well in both outcome discrimination and calibration. Thus, this clinical prediction rule allows accurate stratification of potential CABG candidates before surgery according to the risk of experiencing a major adverse outcome postoperatively.

Aged↗

PubMed1998

Rationale and design of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study that evaluates atorvastatin in unstable angina pectoris and in non-Q-wave acute myocardial infarction.

The goal of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study is to determine whether early, rapid, and profound cholesterol lowering therapy with atorvastatin can reduce early recurrent ischemic events in patients with unstable angina or non-Q-wave acute myocardial infarction. Within 1 to 4 days of hospitalization for one of these conditions, 2,100 patients will be randomly assigned to receive atorvastatin, 80 mg/day, or placebo in a double-blind design. Both groups receive dietary counseling. Over a 16-week follow-up period, the primary outcome measure is the time to occurrence of an ischemic event, defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. Secondary outcome measures are the time to occurrence and incidence of each of the primary outcome components, as well as nonfatal stroke, worsening angina, congestive heart failure requiring hospitalization, and need for coronary revascularization not anticipated before randomization. The sample size of 1,050 patients in each group is expected to provide 95% power to detect a 30% reduction in the primary outcome measure with a 5% level of significance. The results of the MIRACL study will determine the utility of profound cholesterol lowering as an early intervention in acute coronary syndromes.

Angina, Unstable↗

PubMed1999

Primary coronary infarct artery stenting in acute myocardial infarction.

Completed and ongoing randomized trials have provided results that favor primary infarct-related artery (IRA) stenting as opposed to primary percutaneous transluminal coronary angioplasty, but the applicability of the trial results to all patients with acute myocardial infarction (AMI) has not yet been investigated. This study sought to determine the applicability of an unconditional IRA stenting strategy in nonselected patients with AMI. After successful mechanical recanalization of the IRA, all patients with AMI and a reference diameter > or =2.5 mm were considered eligible for primary IRA stenting without any restriction regarding age or clinical status on presentation. The primary end point of the study was a composite end point defined as death, reinfarction, or repeat target lesion revascularization. Primary IRA stenting was successfully performed in 161 of 190 consecutive patients with AMI (85%), and of 162 (99%) considered suitable for stenting. Patients with nonstented IRA had a reference IRA diameter smaller than patients with a stent (2.71+/-0.48 vs 3.20+/-0.41 mm, p <0.001). Overall, the 6-month mortality was 5%. Mortality was 2% for patients without, and 32% for patients with cardiogenic shock. The incidences of reinfarction and of repeat target lesion revascularization were 1% and 12%, respectively. The 6-month angiographic follow-up showed an IRA patency rate of 94% and a restenosis rate of 26%. The results of this study strengthen the hypothesis that unconditional primary IRA stenting is highly feasible, and may actually improve the outcome of patients with AMI.

Adult↗

PubMed2000

Ten-year outcome after coronary angioplasty in patients with single-vessel coronary artery disease and comparison with the results of the Coronary Artery Surgery Study (CASS).

The 10-year results of randomized trials comparing percutaneous transluminal coronary angioplasty (PTCA) in patients with single-vessel coronary artery disease (CAD) with coronary artery bypass grafting (CABG) and medical treatment are not available yet. The aim of this evaluation was to compare our 10-year follow-up results after PTCA in patients with single-vessel CAD with the 10-year follow-up results after CABG and medical treatment in the Coronary Artery Surgery Study (CASS) trial. We evaluated the clinical outcome of 509 patients with single-vessel CAD 10 years after coronary angioplasty. The data were compared with the results of 214 patients with single-vessel CAD after CABG or medical treatment from the CASS trial. End points were defined as death and myocardial infarction. Statistical evaluation was performed by life-table analysis and 2-sided Fisher's exact test. The rate of survival was 86% 10 years after PTCA compared with 85% after CABG and 82% after medical treatment in patients from the CASS trial (p = NS). Survival free from myocardial infarction was 77% after coronary angioplasty, 70% after CABG, and 72% after medical treatment (p = NS). Thus, in patients with single-vessel CAD, infarct-free survival 10 years after coronary angioplasty compared favorably with the results after bypass surgery or medical treatment from the CASS trial.

Adrenergic beta-Antagonists↗

PubMed1995

Prognostic value of predischarge exercise stress echocardiography after acute myocardial infarction.

A predischarge exercise test was performed by 70 patients 7 +/- 4 days (mean +/- SD) after acute myocardial infarction (AMI) to determine the short- and long-term prognostic value of predischarge exercise stress echocardiography (Ex-Echo) compared with exercise stress electrocardiography (Ex-ECG). Two-dimensional echocardiograms were obtained at rest and immediately after exercise; a wall motion score index was obtained both at rest and immediately after exercise. Results of the Ex-Echo were positive in 27 patients (39%), whereas those of Ex-ECG were positive in 34 (49%). The wall motion index after exercise was lower in patients who died during follow-up (85 vs 98, p = 0.01) and in those with cardiac events, defined as death, nonfatal reinfarction, or revascularization (88 vs 98, p = 0.005). More patients with a positive Ex-Echo result had short-term cardiac events (within 2 weeks) than patients with a negative Ex-Echo (6 [22%] vs 2 [5%], p = 0.04). The same was true for long-term mortality (12 [44%] vs 3 [7%], p = 0.0002), reinfarctions (10 [37%] vs 4 [9%], p = 0.01), revascularization procedures (11 [41%] vs 7 [16%], p = 0.023), and cardiac events (22 [81%] vs 12 [28%], p < 0.0001). Survival time was shorter in patients with positive compared with negative Ex-Echo results (34% difference between groups, 95% confidence interval [CI] 10% to 58%, p = 0.002). The same applied for cumulative survival free from cardiac events (43%, p = 0.001, 95% CI 9% to 77%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1996

Regression of Henoch-Schönlein disease with intensive immunosuppressive treatment.

OBJECTIVE: To assess the results of a new immunosuppressive cycle, which had given favorable results in other immune-mediated glomerulonephritides, in the treatment of Henoch-Schönlein disease. METHODS: Eight patients (seven male and one female; age range, 13 to 61 years) with biopsy-proved Henoch-Schönlein were treated with the following protocol: (1) induction with 250 to 750 mg intravenous methylprednisolone every day for 3 to 7 days plus 100 to 200 mg oral cyclophosphamide every day, (2) maintenance with 100 to 200 mg oral prednisone on alternate days plus cyclophosphamide, as before, for 30 to 75 days; (3) tapering, with prednisone reduced on average by 25 mg every month while the cyclophosphamide dose remained the same, and (4) discontinuation, after at least 6 months, with abrupt interruption of cyclophosphamide and slow tapering of prednisone. The results were assessed in terms of remission, improvement, progression of disease, kidney failure, and death, unambiguously defined. The follow-up extended up to 12 years. RESULTS: Seven of eight patients had a complete remission that was maintained indefinitely thereafter. Plasma creatinine levels decreased on average from 211 +/- 81 to 92 +/- 27 mumol/L (p < 0.01) and urine protein excretion decreased from 1.9 +/- 0.8 to 0.3 +/- 0.1 gm/day (p < 0.01). One patient died of intestinal infarction caused by atherosclerotic mesenteric artery thrombosis. CONCLUSIONS: Our data suggest that an intensive immunosuppressive regimen that combines prednisone and cyclophosphamide at high doses can be effective in healing Henoch-Schönlein disease.

Administration, Oral↗

PubMed2003

Role of IgG-seropositivity to Chlamydia pneumoniae in early thrombotic events after coronary stent placement.

AIMS: Since infection of endothelial or smooth muscle cells with Chlamydia pneumoniae increased expression of tissue factor and plasminogen activator inhibitor I (PAI-1), C. pneumoniae might be involved in triggering acute thrombotic events in patients with coronary artery disease. Therefore, we explored a potential relationship between IgG-seropositivity to C. pneumoniae and early thrombotic events after coronary stent placement. METHODS AND RESULTS: In a prospective randomized placebo-controlled study 1010 patients with successful coronary stent placement received roxithromycin or placebo for 4 weeks after coronary stent placement, which showed no effect of roxithromycin on early thrombotic events, as expected. Venous blood samples were collected from patients immediately before treatment. Plasma was analyzed for C. pneumoniae-specific IgG antibody levels by microimmuno-fluorescence. Thrombotic events were defined as death, non-fatal myocardial infarction, or urgent target vessel reintervention within 30 days after stent placement. We found no significant difference concerning the frequency of early thrombotic events in patients positive or negative for C. pneumoniae-specific antibodies. If patients were stratified according to their antibody levels, again no significant difference in the frequency of thrombotic events was observed. CONCLUSION: Our findings do not suggest a role of C. pneumoniae in the development of early complications after stent placement.

Aged↗

PubMed1999

Triglyceride as a risk factor for ischaemic heart disease in British men: effect of adjusting for measurement error.

OBJECTIVE: To assess the influence of differential precision in the measurement of the correlated variables total cholesterol and high density lipoprotein (HDL) cholesterol on the estimates of the risk of ischaemic heart disease (IHD) associated with plasma triglyceride levels. DESIGN, SETTING AND PARTICIPANTS: The Caerphilly Heart Disease Study (CHDS), a prospective cohort study of 2512 middle-aged men living in the town of Caerphilly, south Wales, UK. The results from two sub-studies were used to estimate the degree of measurement imprecision (laboratory error and within-person variation) in triglycerides, total cholesterol and HDL cholesterol. MAIN OUTCOME MEASURES: Multivariable risk estimates for major IHD calculated from logistic regression analysis, adjusted and not adjusted for measurement imprecision. Major IHD events were defined as death from IHD, clinical non-fatal myocardial infarction or electrocardiographic myocardial infarction. RESULTS: There were 261 men with major IHD events during follow-up. In age-adjusted analyses, taking measurement imprecision into account strengthened associations with IHD for all lipid factors. The odds ratio (OR) for one S.D. increase in triglycerides, ignoring measurement imprecision, was 1.36 (95% confidence interval [95% CI] 1.20-1.55) but 1.57 (95% CI 1.30-1.89) when taking imprecision into account. The standardised odds ratio for triglycerides adjusted for measurement imprecision and the two other lipid factors was 1.35 (95% CI 1.09-1.69). In this model, the triglyceride level showed a stronger association than total cholesterol (OR 1.28; 95% CI 1.05-1.56) and HDL cholesterol (OR for one S.D. decrease 1.20; 95% CI 0.97-1.49). When adding fasting blood glucose and diastolic blood pressure, however, the effect of triglycerides was reduced and ceased to be statistically significant (OR 1.19; 95% CI 0.95-1.49). This was further attenuated upon inclusion of body mass index, smoking status and history of pre-existing IHD. Total cholesterol remained a statistically significant (P < 0.05) risk factor in all models. CONCLUSIONS: In contrast to other cohort studies, triglyceride concentration in the CHDS shows an association with the risk of IHD which is independent of total and HDL cholesterol. This effect was pronounced after adjustment for measurement imprecision. It was reduced, however, when adjusted for other factors. While hypertriglyceridaemia may exert an influence independent of other lipid factors, insulin resistance is probably the underlying metabolic disturbance.

Adult↗

PubMed1996

Multivariable predictive models for adverse outcome of invasive meningococcal disease in children.

For prediction of adverse outcome (AO, defined as death or limb amputation) of invasive meningococcal disease (IMD) in children, two multivariable models were derived and validated by reviewing the data in the medical records of patients with IMD, who ranged from birth to 19 years of age, at three pediatric referral hospitals between 1985 and 1990 (derivation set, n = 153, 19 AO) and between 1991 and 1994 (validation set, n = 92, 11 AO). Variables in the derivation set significantly associated with AO (p < 0.05) were entered into a logistic regression analysis. Because coagulation studies (prothrombin time, partial thromboplastin time, and serum fibrinogen concentration) were available for only 50% of patients, two analyses were performed, either excluding (model 1) or including (model 2) coagulation studies. These analyses identified an absolute neutrophil count less than 3000/mm3, poor perfusion, and a platelet count less than 150,000/mm3 (model 1), and a serum fibrinogen concentration less than 2.5 gm/L (250 mg/dl) and an absolute neutrophil count less than 3000/mm3 (model 2), as independent predictors of AO (p < 0.05). When the models were tested on the validation set, the presence of at least two of the three predictors in model 1 had a sensitivity of 82% and a specificity of 97% in predicting AO; the presence of both predictors in model 2 had a sensitivity of 89% and a specificity of 97%. These models can reliably identify patients with IMD at high risk of AO for whom consideration of novel therapies is justified.

Adolescent↗

PubMed2000

Transmyocardial laser revascularization combined with coronary artery bypass grafting: a multicenter, blinded, prospective, randomized, controlled trial.

OBJECTIVE: We sought to assess the safety and efficacy of transmyocardial revascularization combined with coronary artery bypass grafting in patients not amenable to complete revascularization by coronary bypass alone. METHODS: A total of 263 patients whose standard of care was coronary artery bypass grafting and who had one or more ischemic areas not amenable to bypass grafting were prospectively randomized to receive coronary bypass of suitable vessels plus transmyocardial revascularization to areas not graftable (n = 132) or coronary bypass alone with nongraftable areas left unrevascularized (n = 131). Group preoperative demographics and operative characteristics were similar. RESULTS: The operative mortality rate after coronary bypass/transmyocardial revascularization was 1.5% (2/132) versus 7.6% (10/131) after coronary bypass alone (P =.02). Patients undergoing both coronary bypass and transmyocardial revascularization required less postoperative inotropic support (30% vs 55%, P =.0001) and had a trend toward fewer insertions of intra-aortic balloon pumps (4% vs 8%, P =.13) than did patients having coronary bypass alone. Multivariable predictors of operative mortality were coronary artery bypass alone (odds ratio, 5.3; 95% confidence interval, 1.1-25.7; P =.04) and increased age (odds ratio, 1.1; 95% confidence interval, 1. 0-1.2; P =.03). One-year Kaplan-Meier survival (95% vs 89%, P =.05) and freedom from major adverse cardiac events defined as death or myocardial infarction (92% vs 86%, P =.09) favored the combination of coronary bypass and transmyocardial revascularization. Baseline to 12-month improvement in angina and exercise treadmill scores was similar between groups. CONCLUSIONS: In a prospective, randomized, multicenter trial, transmyocardial revascularization combined with coronary artery bypass grafting in patients not amenable to complete revascularization by coronary bypass alone was safe; however, angina relief and exercise treadmill improvement were indistinguishable between groups at 12 months of follow-up. Operative and 1-year survival benefits observed after adjunctive transmyocardial revascularization require confirmation by a larger validation study, which is ongoing.

Coronary Artery Bypass↗

PubMed1998

Thirty-day operative mortality for thoracotomy in lung cancer.

OBJECTIVE: The 30-day operative mortality for thoracotomy in lung cancer is described herein. METHODS: From January 1994 through December 1994, the Japanese Association for Chest Surgery surveyed the number of thoracotomies for lung cancer by operative procedure, age, and operative mortality. The operative mortality was defined as death within 30 days of operation. RESULTS: The total number of operations was 7099. The overall 30-day operative mortality was 1.3%. By operative procedure, the mortalities were 3.2% for pneumonectomy, 1.2% for lobectomy, and 0.8% for a lesser operation, which showed a significant difference between pneumonectomy and lobectomy (p < 0.01). The mortality by age was 0.4% for patients younger than 60 years, 1.3% for those aged 60 to 69, 2.0% for those aged 70 to 79, and 2.2% for those aged 80 or older, which showed significant differences between the less than 60-year and 60- to 69-year-old groups, and between the 60- and 69-year-old and 70- and 79-year-old groups (p < 0.01 and p = 0.047, respectively). Pneumonia and respiratory failure caused most deaths (51.6%). CONCLUSIONS: The operative mortality in Japan for thoracotomy in lung cancer was satisfactorily low. The results of this study on a large population could serve as a standard when discussing the operative outcome of lung cancer.

Age Factors↗

PubMed1999

Prognostic markers in twin pregnancies with an acardiac fetus.

OBJECTIVE: With twin reversed arterial perfusion sequence, the normal cotwin is at risk of heart failure. The purpose of this study was to identify ultrasonographic variables that can help predict prognosis. We hypothesized that variables reflecting the hyperdynamic circulatory condition of the normal fetus and the changes in circulatory impedance in the acardiac mass would correlate with final outcome. METHODS: Ten twin pregnancies with this condition were identified. Follow-up was available for nine. Adverse outcome was defined as death, cardiac failure, or delivery before 30 weeks' gestation for reasons related to the presence of the mass. The following data were collected on the normal fetus: cardiothoracic ratio and left ventricular shortening fraction; and on the mass: maximal length, presence and size of cysts, and presence of a rudimentary heart. The pulsatility index (PI) of the umbilical arteries (UA) of both twins was measured. RESULTS: Four fetuses died, two in utero (22 weeks) and two after cesarean (26 and 31 weeks) for advanced cardiac failure. In the five other cases, the outcome was favorable. The cardiothoracic ratio and presence of cysts or of a rudimentary heart did not correlate with outcome. A PI in the mass' UA significantly lower than that of the normal twin (ratio of 0.71 compared with 1.04 for good outcome, P<.05), an elevated shortening fraction in the second trimester, and a rapid growth rate of the mass were associated with a poor prognosis. CONCLUSION: In pregnancies with twin reversed arterial perfusion sequence, final outcome and treatment decisions can be determined based on hemodynamic criteria.

Adult↗

PubMed2002

Use of localised intracoronary beta radiation in treatment of in-stent restenosis: the INHIBIT randomised controlled trial.

BACKGROUND: In-stent restenosis is a major limitation of intracoronary stenting. Ionising gamma radiation has been shown to reduce recurrence of restenosis after stent placement. We aimed to compare the effects of intracoronary beta radiation treatment with those of placebo for clinical and angiographic outcomes of patients with diffuse in-stent restenosis. METHODS: 332 patients with in-stent restenosis underwent successful coronary intervention, and were then randomly allocated to intracoronary beta radiation with a phosphorus-32 source (n=166) or placebo (166) delivered into a centreing balloon catheter through an automatic afterloader. Longer lesions (>22 mm of dilated length) were treated with tandem positioning of the study wire. The primary safety endpoint was major adverse cardiac events, defined as death, myocardial infarction, and repeat target-lesion revascularisation at 9 months. The primary efficacy endpoint was binary angiographic restenosis rate in the analysis segment during 9-months' follow-up. Analysis was by intention to treat. FINDINGS: Procedural success, and in-hospital and 30-day complications were similar among the two groups. 24 (15%) patients in the radiated group had the primary safety endpoint of death, myocardial infarction, or repeat target-lesion revascularisation over 290 days compared with 51 [corrected] (31%) in the placebo group (difference 16% [95% CI 7-25], p = 0.0006). Binary angiographic restenosis rate was lower in the radiated group than the placebo group for the entire analysed segment (difference 25% [14--37], p < 0.0001). INTERPRETATION: Vascular brachytherapy using pure beta-emitter 32P delivered into a centreing catheter via an automatic afterloader can be used to reduce overall revascularisation in patients undergoing treatment for diffuse in-stent restenosis.

Brachytherapy↗

PubMedDate not supplied

Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study.

BACKGROUND: In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis. METHODS: In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses. FINDINGS: Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported. INTERPRETATION: Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.

Adolescent↗

PubMed2006

Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study.

BACKGROUND: Despite the prognostic value of metabolic syndrome for predicting cardiovascular events, few trials have investigated the effects of statin therapy on cardiovascular morbidity and mortality in patients with the metabolic syndrome. Our post hoc analysis of the Treating to New Targets (TNT) study assessed whether intensive lowering of low-density lipoprotein cholesterol with high-dose atorvastatin therapy results in cardiovascular benefits for patients with both coronary heart disease and the metabolic syndrome. METHODS: The TNT study was a prospective, double blind, parallel-group trial done at 256 sites in 14 countries between April, 1998, and August, 2004, with a median follow-up of 4.9 years. 10,001 patients were enrolled aged 35-75 years with clinically evident coronary heart disease. Our analysis includes 5584 patients with metabolic syndrome based on the 2005 NCEP ATP III criteria. Patients were randomly assigned to receive either atorvastatin 10 mg per day (n=2820) or 80 mg per day (n=2764). The primary outcome measure was time to first major cardiovascular event, defined as death from coronary heart disease, non-fatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or non-fatal stroke. FINDINGS: In patients with coronary heart disease and metabolic syndrome, mean on-treatment low-density lipoprotein cholesterol concentrations at 3 months were 2.6 mmol/L (99.3 mg/dL) with atorvastatin 10 mg, and 1.9 mmol/L (72.6 mg/dL) with atorvastatin 80 mg. At a median follow-up of 4.9 years, major cardiovascular events occurred in 367 (13%) patients receiving atorvastatin 10 mg, compared with 262 (9.5%) receiving atorvastatin 80 mg (hazard ratio 0.71; 95% CI 0.61-0.84; p<0.0001). Irrespective of treatment assignment, significantly more patients with metabolic syndrome (11.3%) had a major cardiovascular event at a median of 4.9 years than those without metabolic syndrome (8.0%; hazard ratio 1.44; 95% CI 1.26-1.64; p<0.0001). This increased risk was significantly reduced by intensive therapy with atorvastatin 80 mg beyond that achieved with atorvastatin 10 mg. INTERPRETATION: These data indicate that patients with coronary heart disease and metabolic syndrome derive incremental benefit from high-dose atorvastatin therapy, irrespective of the presence of diabetes.

Adult↗

PubMed2006

A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial.

BACKGROUND: Long-term data from randomised trials on the consequences of treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST trial, which compared initial treatment strategies for clinical, immunological, and virological outcomes. METHODS: Between 1999 and 2002, 1397 antiretroviral-treatment-naive patients, presenting at 18 clinical trial units with 80 research sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI; n=464). Primary endpoints were a composite of an AIDS-defining event, death, or CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI comparison, and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison. Analyses were by intention-to-treat. This study is registered ClinicalTrials.gov, number NCT00000922. FINDINGS: 1397 patients were assessed for the composite endpoint. A total of 388 participants developed the composite endpoint, 302 developed AIDS or died, and 188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for AIDS or death, for death, and for virological failure were 1.02 (95% CI 0.79-1.31), 1.07 (0.80-1.41), 0.95 (0.66-1.37), and 0.66 (0.56-0.78), respectively. 1196 patients were assessed for the three-class versus combined two-class primary endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per mm3 and +227 cells per mm3 for the three-class and the combined two-class strategies (p=0.62), respectively. HRs (three-class vs combined two-class) for AIDS or death and virological failure were 1.15 (0.91-1.45) and 0.87 (0.75-1.00), respectively. HRs (three-class vs combined two-class) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm3 (p=0.38 for interaction), and for participants with baseline HIV RNA concentrations less than 100 000 copies per mL and 100,000 copies per mL or more (p=0.26 for interaction). Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies (HR 1.58; p<0.0001). INTERPRETATION: Initial treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV.

Adult↗

PubMed1998

Systematic review of early prediction of poor outcome in anoxic-ischaemic coma.

BACKGROUND: Studies to assess the prognostic value of early neurological and neurophysiological findings in patients with anoxic-ischaemic coma have not led to precise, generally accepted, prognostic rules. We did a systematic review of the relevant literature to assess whether such rules could be derived from the combined results of these studies. METHODS: From Medline and Embase databases we selected studies concerning patients older than 10 years with anoxic-ischaemic coma in which findings from early neurological examination, electroencephalogram (EEG), or somatosensory evoked potentials (SSEP) were related to poor outcome--defined as death or survival in a vegetative state. We selected variables with a specificity of 100% for poor outcome in all studies, and expressed the overall prognostic accuracy of these variables as pooled positive-likelihood ratios and as 95% CIs of the pooled false-positive test rates. FINDINGS: In 33 studies, 14 prognostic variables were studied, three of which had a specificity of 100%: absence of pupillary light reflexes on day 3 (pooled positive-likelihood ratio 10.5 [95% CI 2.1-52.4]; 95% CI pooled false-positive test rate 0-11.9%); absent motor response to pain on day 3 (16.8 [3.4-84.1]; 0-6.7%); and bilateral absence of early cortical SSEP within the first week (12.0 [5.3-27.6]; 0-2.0%). EEG recordings with an isoelectric or burst-suppression pattern had a specificity of 100% in five of six relevant studies (pooled positive-likelihood ratio 9.0 [2.5-33.1]; 95%CI pooled false-positive test rate 0.2-5.9%). These characteristics were present in 19%, 31%, 33%, and 33% of pooled patient populations, respectively. For the 11 SSEP studies, results did not significantly differ between studies in which the treating physicians were or were not masked from the test result, prospective and retrospective studies, studies with short and long follow-up periods, and studies with high or low overall poor outcome. INTERPRETATION: SSEP has the smallest CI of its pooled positive-likelihood ratio and its pooled false-positive test rate. Because evoked potentials are also the least susceptible to metabolic changes and drugs, recording of SSEP is the most useful method to predict poor outcome.

Adolescent↗