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| CARDIOVASCULAR NEWS |
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| Year : 2004 | Volume
: 5
| Issue : 1 | Page : 2-7 |
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Cardiovascular News
| Date of Web Publication | 22-Jun-2010 |
Correspondence Address:
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How to cite this article:
. Cardiovascular News. Heart Views 2004;5:2-7 |
Serum Deoxyribonuclease I: A New Early-Phase Marker in Acute Myocardial Infarction?
The delayed release of serum cardiac markers such as creatine kinase isoenzyme MB and equivocal early electrocardiographic changes have hampered a diagnosis of acute myocardial infarction (AMI) in the early phase after its onset. Therefore, a reliable serum biochemical marker for the diagnosis of AMI in the very early phase is desirable.
Deoxyribonuclease I (DNase I) was the first enzyme to be recognized as specific for DNA. One of its proposed roles is DNA breakdown during apoptosis. DNase I has been detected in human myocardium, and it has been reported that the activity level increases in heart failure due to idiopathic dilated cardiomyopathy. However, the association between serum DNase I activity level and coronary heart disease (CHD) has not yet been clarified. In the present study, the authors assessed the serum DNase I activity in patients with AMI and related CHD and found that there is a specific elevation of serum DNase I activity in the very early stages of AMI. The authors suggest that serum DNase I activity could be used as a new diagnostic marker for the early detection of AMI.
Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment-Elevation Myocardial Infarction
The clinical benefits of insulin previously observed in acute ST-segment-elevation myocardial infarction (STEMI) may be partially explained by an anti-inflammatory effect. This potential effect of insulin in STEMI patients treated with fibrinolytics was assessed.
Thirty-two patients receiving reteplase were randomly assigned infusions of either insulin at 2.5 U/h, dextrose, and potassium (GIK) or normal saline and potassium (C) for 48 hours. Plasma concentrations of high-sensitivity C-reactive protein (CRP), serum amyloid A (SAA), plasminogen activator inhibitor-1 (PAI-1), creatine kinase (CK), and CK-MB were measured at baseline and sequentially for 48 hours. Total p47phox protein in mononuclear cells was measured in a subgroup of 13 subjects. Baseline CRP and SAA were significantly increased (2- to 4-fold) at 24 and 48 hours in each group (P<0.01). However, in the insulin group, there was a significant (P<0.05) attenuation of the absolute rise in concentration of CRP and SAA from baseline. The absolute increase of CRP and SAA was reduced by 40% (CRP) and 50% (SAA) at 24 hours and at 48 hours compared with the control group. The absolute increase in PAI-1 from baseline and the percentage increase in p47phox over 48 hours were significantly (P<0.05) lower in the insulin-treated group. CK-MB peaked earlier and tended to be lower in insulin-treated subjects, especially in patients with inferior MI.
Insulin has an anti-inflammatory and profibrinolytic effect in patients with acute MI. These effects may contribute to the clinical benefits of insulin in STEMI.
Cardiovascular Events in Diabetic and Nondiabetic Adults With or Without History of Myocardial Infarction (ARIC)
Whether diabetic patients without a history of myocardial infarction (MI) have the same risk of coronary heart disease (CHD) events as nondiabetic patients with a history of MI remains controversial. Risks of CHD and stroke events and mortality from cardiovascular disease (CVD) in diabetic and nondiabetic men and women with and without a history of MI were compared.
We followed a total of 13,790 African American and white men and women ages 45 to 64 years who participated in the Atherosclerosis Risk in Communities study, beginning in 1987 to 1989. There were 634 fatal CHD or nonfatal MI events, 312 fatal or nonfatal strokes, and 358 deaths from CVD during an average of 9 years of follow-up (125 998 person-years). After adjustment for age, sex, race, Atherosclerosis Risk in Communities field center, and multiple baseline risk factors, patients who had a history of MI without diabetes at baseline had 1.9 times the risk of fatal CHD or nonfatal MI (95% CI, 1.35 to 2.56; P<0.001) compared with diabetic patients without a prior history of MI. The nondiabetic patients with MI also had 1.8 times the risk of CVD mortality compared with diabetic patients without MI (95% CI, 1.22 to 2.72; P=0.003). However, stroke risk was similar between diabetic patients without MI and nondiabetic patients with MI (RR, 1.05; 95% CI, 0.61 to 1.79; P=0.87). We also observed that nondiabetic patients with MI had a carotid artery wall thickness similar to diabetic patients without MI (P=0.77).
Diabetic patients without MI had lower risk of CHD events and mortality from CVD compared with nondiabetic patients with MI, but stroke risk was similar between these 2 groups.
In-Stent Intimal Hyperplasia in Diabetic Patients Treated With or Without Abcimixab (DANTE Trial)
In diabetic patients in the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, abciximab reduced target vessel revascularization by 50% compared with placebo. Whether this is a result of a lower restenosis rate caused by inhibition of intimal hyperplasia remains to be defined.
The purpose of this study was to determine whether abciximab at the time of stent implantation would reduce in-stent intimal hyperplasia measured by intravascular ultrasound at 6-month follow-up in type 2 diabetics. Ninety-six diabetic patients (96 lesions) who underwent elective stent implantation for a de novo lesion in a native coronary artery were randomly assigned to receive abciximab or no abciximab. In-stent intimal hyperplasia volume, expressed as percentage of stent volume, did not differ between groups: 41.3±21.0% for those treated with abciximab versus 40.5±18.3% for those treated without abciximab (P=0.9). There were also no significant differences in angiographic minimal luminal diameter at follow-up (1.74±0.69 versus 1.66±0.63 mm; P=0.5), late loss (1.03±0.63 versus 1.07±0.58 mm; P=0.7), restenosis rate (17.8% versus 22.9%; P=0.5), or cumulative incidence of major adverse cardiac events at 12 months (19.1% versus 20.4%; P=0.9).
Six-month intravascular ultrasound volumetric analysis showed that abciximab, at the time of coronary stent implantation, was not associated with a reduction of in-stent intimal hyperplasia in diabetic patients.
Clinical and Angiographic Predictors of Restenosis after stent deployment in diabetic patients
Restenosis and consequent adverse cardiac events are increased in diabetics undergoing percutaneous coronary intervention. Use of intracoronary stents may ameliorate such risks; however, factors influencing the likelihood of restenosis after stent deployment in this high-risk patient subgroup are unknown.
All stented diabetic patients in 16 studies of percutaneous coronary intervention, all of which underwent core angiographic analysis were retrospectively analyzed at Cardialysis, Rotterdam. Univariate and multivariate analyses, with 37 clinical and angiographic variables, compared those with and without restenosis and predicted restenosis rates calculated through the use of reference charts derived from angiographic data.
Within the studies, 418 of 3090 (14%) stented patients with 6-month angiographic follow-up had diabetes. Restenosis (50% diameter stenosis at follow-up) occurred in 550 of 2672 (20.6%) nondiabetic and 130 of 418 (31.1%) diabetic patients (P<0.001). Univariate predictors of restenosis in diabetics were smaller vessel reference diameter (RD) (P<0.001), smaller minimal luminal diameter before stenting (P=0.01), smaller minimal luminal diameter and percent diameter stenosis after stenting (P<0.001, P=0.04), greater stented length of vessel (P<0.001), and reduced body mass index (BMI) (P=0.04). With the use of multivariate analysis, only smaller RD (P=0.003), greater stented length of vessel (P=0.04), and reduced BMI (P=0.04) were associated with restenosis. Reference charts demonstrated an incremental risk of restenosis that appears solely dependent on vessel RD.
Restenosis after stent deployment is significantly increased in diabetic patients. Vessel caliber, stented length of vessel, and lower BMI are predictors of in-stent restenosis in patients with diabetes. Furthermore, vessel caliber affected the predicted risk of restenosis incrementally.
Effects of GP Ib/IIIa Inhibition and Coronary Artery Stenting in the Invasive Management of Unstable Angina/Non-ST-Elevation Myocardial Infarction
Effects of GP IIb/IIIa Inhibition and Coronary Artery Stenting in the Invasive Management of Unstable Angina/Non-ST-Elevation Myocardial Infarction
TIMI IIIB and TACTICS-TIMI 18 were 2 trials of an early invasive strategy in unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI) that were conducted nearly a decade apart but with virtually identical enrollment criteria and designs, except that upstream glycoprotein IIb/IIIa inhibition was mandated and coronary artery stenting was routinely used in TACTICS-TIMI 18. Investigators sought to examine the effect of these advances on clinical outcomes and the benefits of an early invasive strategy in UA/NSTEMI by comparing the results of TIMI IIIB and TACTICS-TIMI 18 trials.
Patients were stratified on the basis of their TIMI risk score into low-, intermediate-, and high-risk categories. Within each risk category, the rates of clinical outcomes and the benefit of an early invasive strategy were compared. Compared with patients in TIMI IIIB and adjusting for baseline risk, patients in TACTICS-TIMI 18 had lower rates of death, MI, or rehospitalization for acute coronary syndromes (OR, 0.62; P<0.0001). Across both trials, the benefit of an early invasive strategy was significantly greater with increasing baseline risk: OR, 1.39 in low-risk, 0.80 in intermediate-risk, and 0.57 in high-risk patients (P ≤ 0.004 for interactions). After adjustment for baseline risk, an early invasive strategy tended toward a more favorable result in TACTICS-TIMI 18 than in TIMI IIIB (OR, 0.79; 95% CI, 0.56 to 1.11).
Advances in the care of patients with UA/NSTEMI, including glycoprotein IIb/IIIa inhibition and stenting, were associated with lower rates of death, MI, and rehospitalization for acute coronary syndromes and a trend toward a greater benefit of an early invasive strategy.
The Medical Therapy, angioplasty, or surgery for multivessel coronary artery disease?
Despite routine use of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI), there is no conclusive evidence that either one is superior to medical therapy (MT) alone for the treatment of multivessel CAD.
The relative efficacies of three possible therapeutic strategies for patients with multivessel coronary artery disease (CAD), stable angina, and preserved ventricular function were evaluated. The primary end point was defined as cardiac mortality, Q-wave myocardial infarction (MI), or refractory angina requiring revascularization. All data were analyzed according to the intention-to-treat principle.
A total of 611 patients were randomly assigned to either a CABG (n = 203), PCI (n = 205), or MT (n = 203) group. The one-year survival rates were 96.0% for CABG, 95.6% for PCI, and 98.5% for MT. The rates for one-year survival free of Q-wave MI were 98% for CABG, 92% for PCI, and 97% for MT. After one-year follow-up, 8.3% of MT patients and 13.3% of PCI patients underwent additional interventions, compared with only 0.5% of CABG patients. At one-year follow-up, 88% of the patients in the CABG group, 79% in the PCI group, and 46% in the MT group were free of angina (p < 0.0001).
Medical therapy for multivessel CAD was associated with a lower incidence of short-term events and a reduced need for additional revascularization, compared with PCI. In addition, CABG was superior to MT for eliminating anginal symptoms. All three therapeutic regimens yielded relatively low rates of cardiac-related deaths.
Beta-blocker therapy improves clinical outcomes in AMI after successful primary angioplasty
It has been shown that pre-treatment with beta-blockers has a beneficial effect on short-term clinical outcomes in patients undergoing primary PCI for AMI. It is unknown if beta-blocker therapy after successful primary PCI improves prognosis of AMI. The effect of beta-blocker therapy on clinical outcomes in the setting of acute myocardial infarction (AMI) after successful primary percutaneous coronary intervention (PCI) was studied.
Investigators analyzed clinical, angiographic, and outcomes data in 2,442 patients who underwent successful primary PCI in the Primary Angioplasty in Acute Myocardial Infarction-2 (PAMI-2), PAMI No Surgery-on-Site (PAMI noSOS), Stent PAMI, and Air PAMI trials. Patients were classified into beta group (those who received beta-blockers after successful PCI, N = 1,661) and no-beta group (n = 781). We compared death and major adverse cardiac events (MACE) (death, reinfarction, and ischemia-driven target vessel revascularization) at six months between groups receiving and not receiving beta-blockers.
At six months, beta patients were less likely to die (2.2% vs. 6.6%, p < 0.0001) or experience MACE (14 vs. 17%, P = 0.036). In multivariate analysis, beta-blockers were independently associated with lower six-month mortality (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.26 to 0.73, P = 0.0016). Beta-blocker therapy was an independent predictor of lower six-month events in high-risk subgroups: ejection fraction 50% (death: OR 0.34, 95% CI 0.19 to 0.60, P = 0.0002) or multi-vessel coronary artery disease (CAD) (death: OR 0.26, 95% CI 0.14 to 0.48, p < 0.0001; MACE: OR 0.57, 95% CI 0.41 to 0.80, P = 0.0011).
Treatment with beta-blockers after successful primary PCI is associated with reduced six-month mortality, with the greatest benefit in patients with a low ejection fraction or multi-vessel CAD.
Effect of IV Beta-Blockade before primary angioplasty on survival in AMI patients
Studies of primary PCI but not thrombolysis have suggested that beta-blocker administration before reperfusion may enhance survival. Whether oral beta-blocker use before admission modulates this effect is unknown. Hence, the effect of intravenous beta-blockers administered before primary percutaneous coronary intervention (PCI) on survival and myocardial recovery after acute myocardial infarction (AMI) was studied.
The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial randomized 2,082 AMI patients to either stenting or balloon angioplasty, each ± abciximab. In accordance with the protocol, intravenous beta-blockers were administered before PCI in the absence of contraindications.
A total of 1,136 patients (54.5%, BB+ group) received beta-blockers before PCI, whereas 946 (45.5%, BB - group) did not. The 30-day mortality was significantly lower in the BB+ group than in the BB - group (1.5% vs. 2.8%, P = 0.03), an effect entirely limited to patients who had not been receiving beta-blockers before admission (1.2% vs. 2.9%, P = 0.007). In contrast, no survival benefit with pre-procedural beta-blockers was observed in patients receiving beta-blockers at home (3.3% vs. 1.9%, respectively, P = 0.47). By multivariate analysis, pre-procedural beta-blocker use was an independent predictor of lower 30-day mortality among patients without previous beta-blocker therapy (relative RISK = 0.38 [95% confidence interval 0.17 to 0.87], P = 0.02). The improvement in left ventricular ejection fraction from baseline to seven months was also greater after intravenous beta-blockers (3.8% vs. 1.3%, P = 0.01), an effect limited to patients not receiving oral beta-blockers before admission.
In patients with AMI undergoing primary PCI, myocardial recovery is enhanced and 30-day mortality is reduced with pre-procedural intravenous beta-blockade. The effects were confined to patients untreated with oral beta-blocker medication before admission.
Predictors of Outcome After Alcohol Septal Ablation Therapy in Patients with Hypertrophic Obstructive Cardiomyopathy
Alcohol septal ablation (ASA) therapy results in clinical and hemodynamic improvement in patients with hypertrophic obstructive cardiomyopathy. However, a subset remains symptomatic afterward, requiring additional procedures. Investigators sought to examine the determinants of an unsatisfactory outcome, defined as unchanged symptoms with <50% reduction of baseline left ventricular outflow tract (LVOT) gradient.
Of 173 consecutive hypertrophic obstructive cardiomyopathy patients who underwent ASA, 39 had an unsatisfactory outcome after the first procedure. Patients with an unsatisfactory outcome had a higher baseline LVOT gradient, fewer septal arteries injected with ethanol, lower peak creatine kinase (CK), smaller septal area opacified by contrast echocardiography, and higher residual gradient in the catheterization laboratory after ASA (all P<0.05). Symptoms, septal thickness, mitral regurgitation severity, and ventricular function were not determinants of outcome. On multiple logistic regression, LVOT gradient reduction after ASA in the catheterization laboratory to 25 mmHg (OR, 5.5; P=0.01) and peak CK <1300 U/L (OR, 2.5; P=0.04) were the independent predictors of an unsatisfactory outcome.
The residual LVOT gradient in the catheterization laboratory and peak CK leak after ASA are the independent predictors of ASA outcome.
In-Hospital Morbidity in Off-pump CABG not Lower Compared to On-Pump CABG
There is increasing evidence that cardiopulmonary bypass (CPB) may be responsible for the morbidity associated with coronary artery bypass grafting (CABG) surgery. Recent developments in cardiac stabilization devices have made CABG without CPB feasible. However, there is conflicting evidence to date from published trials comparing outcomes between CABG performed with and without CPB, with some trials indicating an advantage to the avoidance of CPB and others showing little benefit.
In a single-center randomized trial, 300 patients requiring CABG surgery at a single institution were prospectively randomized to have the procedure performed with CPB (n=150) or on the beating heart (n=150). Exclusion criteria for the trial included emergency procedure, concomitant major cardiac procedures, ejection fraction <30%, and reoperation. In-hospital outcomes were analyzed on an intention-to-treat basis. A mean of 3.0±0.9 grafts were performed in the CPB group compared with 2.8±0.9 grafts in the beating-heart group (P=0.06). There were no significant differences between the CPB group and the beating-heart group in mortality (0.7% versus 1.3%; P=1.0), transfusion (8.7% versus 9.3%), perioperative myocardial infarction (0.7% versus 2.7%; P=0.37), permanent stroke (0% versus 1.3%; P=0.50), new atrial fibrillation (32% versus 25%; P=0.20), and deep sternal wound infection (0.7% versus 0%; P=1.0). The mean time to extubation was 4 hours, the mean stay in the intensive care unit was 22 hours, and the median length of hospitalization was 5 days in both groups (P=NS).
The investigators conclude that in contrast to published trials, their study did not demonstrate any advantage with CABG performed without CPB in terms of patient morbidity. Excellent results can be obtained with either surgical approach.
Cardiac-Resynchronization Therapy with or without an Implantable Defibrillator in Advanced Chronic Heart Failure
The study sought to determine whether biventricular pacing with or without and implantable deibrillator (ICD) reduce the risk of death and hospitalization in patients with Class III-IV congestive (CHF) and a bundle branch block.
In this multicenter trial (COMPANION), 1,520 patients (mean age 67 years) with class III-IV CHF (mean ejection fraction 21%) and a QRS duration >120 ms were randomly assigned to receive optimal pharmacologic therapy for CHF (control group, 308 patients), a biventricular pacemaker (617 patients), or a biventricular pacemaker-ICD (595 patients). The duration of follow-up was 12-16 months in the three study groups.
The one-year incidence of death/hospitalization from any cause was 68% in the control group. There was a relative risk reduction in this end point of 20% in both groups that received a biventricular pacemaker. Biventricular pacing improved quality of life, CHF class, and functional capacity. Compared to the control group, death from any cause was lowered significantly by biventricular pacing-ICD therapy (relative risk reduction 36%), but not by biventricular pacing by itself.
Biventricular pacing with or without an ICD reduces the combined risk of death/hospitalization from any cause in patients with severe CHF and bundle branch block, whereas only the biventricular pacemaker-ICD reduces total mortality.
Lipid-Lowering Therapy Following Major Noncardiac Surgery Reduce In-Hospital Mortality
Cardiovascular complications following major noncardiac surgery are an important source of perioperative morbidity and mortality. What is the association between treatment with lipid-lowering medications and in-hospital mortality following major noncardiac?
The study was a retrospective cohort study of 780,591 patients aged 18 years or older who underwent major noncardiac surgery from January 1, 2000, to December 31, 2001, at 329 hospitals throughout the United States. Only patients who survived through at least the second hospital day were included. Lipid-lowering therapy was defined as use during the first two hospital days. Propensity matching was used to adjust for numerous baseline differences. The primary outcome was in-hospital mortality.
Of the 780,591 patients, 77,082 patients (9.9%) received lipid-lowering therapy perioperatively and 23,100 (2.96%) died during the hospitalization. Treatment with lipid-lowering agents was associated with lower crude mortality (2.13% vs 3.05%, P<.001). After adjusting for residual differences in the propensity matched groups using conditional logistic regression, risk of mortality remained lower among treated patients (adjusted odds ratio [OR], 0.62; 95% confidence interval [CI], 0.58-0.67). Based on this adjusted OR, the number needed to treat to prevent a postoperative death in the propensity matched cohort was 85 (95% CI, 77-98) and varied from 186 among patients at lowest risk to 30 among those with a revised cardiac risk index score of four or more. In a further analysis using the entire study cohort and adjusting for quintile of propensity, a significant effect of treatment persisted (adjusted OR, 0.71; 95% CI, 0.67-0.75).
The authors concluded that treatment with lipid-lowering agents may reduce risk of death following major noncardiac surgery.
Thrombus formation is a risk associated with LA ablation procedures
This study reports the incidence of, risk factors for, and management of left atrial (LA) thrombus documented by intracardiac echocardiography (ICE) during LA ablation for atrial fibrillation (AF).
Intracardiac echocardiography imaging was performed in 232 patients (184 men, average age 55 ± 11 years) with AF undergoing pulmonary vein ostial ablation.
Anticoagulation (activated clotting time >250 s) was maintained after dual transseptal catheterization. Left atrial thrombus (n = 30) was observed in 24 of 232 patients (10.3%). Thrombi measured 12.9 ± 11.1 mm (length) and 2.2 ± 1.3 mm (width) and were attached to a sheath or mapping catheter. Most thrombi (27 of 30, 90%) were eliminated from the LA by withdrawal of the sheath and catheter into the right atrium (RA). Two thrombi became wedged in the interatrial septum and incompletely withdrawn into the RA, and one was recognized only on post-procedure review of ICE images. Patients with LA thrombus had an increased LA diameter (4.8 ± 0.5 vs. 4.5 ± 0.6 cm, p < 0.02), spontaneous echo contrast (67% vs. 3%, p < 0.0001) and a history of persistent AF (29% vs. 6%, p < 0.0002). Multivariate discriminant analysis showed that spontaneous echo contrast (f = 97.9, p < 0.0001) was the most important determinant of LA thrombus formation. No patient with LA thrombus suffered a clinical thromboembolic complication.
Left atrial thrombus identified on ICE may occur during LA catheter ablation procedures despite aggressive anticoagulation. Spontaneous echo contrast may predict risk for LA thrombus formation. Left atrial thrombus may be successfully withdrawn into the RA under ICE imaging with no overt complications.
Antiischemic Therapy at the Time of Testing Affects Prognostic Value of Pharmacological Stress Echocardiography
The aim of this study was to determine whether antianginal medications affect the prognostic value of pharmacological stress echocardiography.
From the EPIC (Echo-Persantine International Cooperative and EDIC Echo-Dobutamine International Cooperative) Data Bank, and (7333 patients (5452 men; age; 59 ± 10 years) underwent pharmacological stress echocardiography with either high-dose dipyridamole (0.84 mg/kg over 10 minutes; n = 4984) or high-dose dobutamine (up to 40 μg · kg-1 · min-1; n=2349) (DET) for diagnostic purposes. At the time of testing, 1791 patients were on antiischemic therapy (nitrates and/or calcium antagonists and/or b-blockers). Patients were followed up for a mean of 2.6 years (range, 1 to 206 months). DET was positive for myocardial ischemia in 2854 patients (39%) and negative in 4479 (61%). Total mortality was 336 (4.5%). Death was attributed to cardiac causes in 161 patients (2.1%). Survival was highest in patients with negative DET off therapy and lowest in patients with positive DET studied on therapy (95% versus 81%; P=0.0000). Survival was comparable in patients with a negative test on therapy and in patients with a positive test off therapy (88% versus 84%, P=NS).
Ongoing antiischemic therapy at the time of testing heavily modulates the prognostic value of pharmacological stress echo. In the presence of concomitant antiischemic therapy, a positive test is more prognostically malignant, and a negative test less prognostically benign.
Effects of Conjugated Equine Estrogen in Postmenopausal Women with Hysterectomy. The Women's Health Initiative Randomized Controlled Trial
Does postmenopausal hormone replacement therapy reduce the prevalence of chronic diseases?
A randomized, double-blind, placebo controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative (WHI) began in 1993 and enrolled 10,739 postmenopausal women, aged 50-79 years, with a prior hysterectomy. Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. Primary outcome was coronary heart disease (CHD) incidence, (nonfatal myocardial infarction or CHD death), and invasive breast cancer incidence was the primary safety outcome. The summary overall effect was expressed via a global index of risks and benefits: primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes.
The mean age at entry was 63 years, 31% were 50-59years, and 25% were non-white. Age at the time of the hysterectomy was less than 50 years in 82%, and 40% had undergone bilateral oophorectomy. About 52% had not used prior CEE. BMI averaged over 30kg/m2, about 10% were current smokers, 15% had elevated cholesterol, and nearly 50% had hypertension, and 12% had CVD at baseline. In 2004 the National Institutes of Health ended the trial early. The incident number of cases and estimated hazard ratios (HRs) and 95%CI for CEE versus placebo for the major clinical outcomes at an average follow-up 6.8 years were: 376 CHD, 0.91 (0.75-1.12); 218 breast cancer, 0.77 (0.59-1.01); 276 strokes, 1.39 (1.10-1.77); 85 PE, 1.34 (0.87-2.06); 119 colorectal cancers, 1.08 (0.75-1.55); 102 hip fractures, 0.61 (0.41-0.91). Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10,000 person-years and an absolute risk reduction of six fewer hip fractures per 10,000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant two events per 10,000 person-years.
The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.
[ Perspective: This study of CEE was conducted in a high-risk group, and is one of many high quality clinical trials demonstrating why placebo controlled trials are necessary prior to incorporating drug therapy into practice based simply on biologic plausibility or observational studies. However, the size of this study and the relatively low incremental risk (1.2 per 1000 patient-years) of strokes and very small (2 per 10,000 patient-years) excess risk of all events allows the woman and her physician to decide whether estrogen therapy targeting postmenopausal symptoms is worth it after weighing the knowledge regarding risk and benefits. (Source Content provided by the American College of Cardiology Foundation); Cardiosource.com
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