Cochrane for Clinicians
Putting Evidence into Practice
Early Invasive Therapy or Conservative Management for Unstable Angina or NSTEMI?
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Clinical Scenario
A 58-year-old man presents to the hospital after 30 minutes of chest pressure and diaphoresis. Electrocardiography shows ST-segment depressions in the inferior leads, and the first set of cardiac enzymes are mildly elevated. The resident asks whether the patient needs to be transported to a facility able to perform heart catheterization.
Clinical Question
How effective is early invasive treatment of patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI) compared with conservative management?
Evidence-Based Answer
Compared with conservative management, early invasive treatment of patients with UA or NSTEMI using coronary angiography with or without revascularization reduces rehospitalization and refractory angina within the first year and significantly reduces mortality and myocardial infarction at two to five years. Patients undergoing early invasive treatment are more likely to have short-term complications such as bleeding and procedure-related myocardial infarction.1
Cochrane Abstract
Background: In patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), two strategies are possible. The first is a routine invasive strategy, in which all patients undergo coronary angiography shortly after admission and, if indicated, coronary revascularization. The second is a conservative strategy, in which medical therapy alone is used initially, with patients selected for angiography based on clinical symptoms or investigational evidence of persistent myocardial ischemia.
Objectives: To determine the benefits of an invasive compared with a conservative strategy for treating UA/NSTEMI in the stent era.
Search Strategy: The Cochrane Central Register of Controlled Trials (Issue 3 2005), Medline, and EMBASE were searched from 1996 to September 2005 with no language restrictions.
Selection Criteria: Included studies were prospective trials comparing invasive with conservative strategies in UA/NSTEMI.
Data Collection and Analysis: The authors1 identified five studies (7,818 participants). Using intention-to-treat analysis with random effects models, summary estimates of relative risk (95% confidence interval [CI]) were determined for primary end points of all-cause death; fatal or nonfatal myocardial infarction; all-cause death or nonfatal myocardial infarction; and refractory angina. Further analysis of included studies was undertaken depending on whether glycoprotein IIb/IIIa receptor antagonists were used routinely. Heterogeneity was assessed using chi-square and variance (I2) methods.
Primary Results: In the all-study analysis, mortality during initial hospitalization showed a trend to hazard with an invasive strategy (relative risk = 1.59; 95% CI, 0.96 to 2.64). Mortality and myocardial infarction assessed at two to five years in two trials were significantly decreased by an invasive strategy (relative risks = 0.75 [95% CI, 0.62 to 0.92] and 0.75 [95% CI, 0.61 to 0.91], respectively). The composite end point of death or nonfatal myocardial infarction was significantly decreased by an invasive strategy at several time points after initial hospitalization. The incidences of early (i.e., less than four months) and intermediate (i.e., six to 12 months) refractory angina were significantly decreased by an invasive strategy (relative risks = 0.47 [95% CI, 0.32 to 0.68] and 0.67 [95% CI, 0.55 to 0.83], respectively), as were early and intermediate rehospitalization rates (relative risks = 0.60 [95% CI, 0.41 to 0.88] and 0.67 [95% CI, 0.61 to 0.74], respectively). The invasive strategy was associated with a twofold increase in the relative risk of periprocedural myocardial infarction (as variably defined) and a 1.7-fold increase in the relative risk of bleeding.
Reviewers' Conclusions: An early invasive strategy is preferable to a conservative strategy in the treatment of UA/NSTEMI.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (http://www.cochrane.org).
Practice Pointers
Many patients with ischemic heart disease present to a primary care physician or emergency department with acute coronary syndrome (which encompasses UA, NSTEMI, and ST-segment elevation myocardial infarction [STEMI]).2 Patients with NSTEMI have elevated cardiac enzymes, whereas those with UA do not. Emergency coronary angiography followed by appropriate stenting or coronary artery bypass grafting (CABG) has become the preferred treatment for STEMI. For patients with UA or NSTEMI, there are two treatment strategies: routine coronary angiography (with or without coronary revascularization) or conservative management (i.e., medical therapy alone with angiography in select patients). The authors of this Cochrane review examined the evidence to determine whether emergent coronary angiography is more beneficial than conservative management for patients with UA or NSTEMI.
Five randomized controlled trials published between 1999 and 2005 were included in the review. The studies were heterogenous, making cross comparison difficult. The number of participants in each study ranged from 131 to 2,457. Patients with persistent STEMI were uniformly excluded, but inclusion criteria varied. Patients with and without a history of known coronary artery disease (CAD) were included. Two of the five studies included only patients with elevated cardiac enzymes; the other three studies included patients with angina and cardiac enzyme elevation, electrocardiography changes, or a history of CAD. Thus, some of the patient populations may have been at higher risk of persistent myocardial ischemia than others. The study durations also varied, and only two of the studies lasted longer than one year.
Conservative management strategies differed among the studies. Aspirin, some form of heparin, and statins were used in all studies, but the use of beta blockers, angiotensin-converting enzyme inhibitors, and clopidogrel (Plavix) varied. Glycoprotein IIb/IIIa receptor antagonists were used heavily in the early invasive groups of two of the studies, and in one of these studies they also were used in the conservative management group. Patients in the conservative management groups had access to coronary angiography, but only if medication management failed, angina persisted, electrocardiography changes evolved, or stress testing results were positive. By the various end points of the studies, the revascularization rates by stent, CABG, or both ranged from 61 to 79 percent among the early invasive groups and 38 to 54 percent among the conservative management groups.
The authors conclude that an early invasive strategy is preferable to a conservative management strategy in the treatment of patients with UA or NSTEMI; however, the absolute difference between strategies in long-term mortality was not large. Forty-three people would need to be treated with an early invasive strategy to prevent one death at two to five years (i.e., number needed to treat [NNT] = 43), and a comparable number of patients will experience bleeding or procedure-related myocardial infarction (number needed to harm [NNH] = 36 and 35, respectively). However, there was a clear benefit with early invasive treatment in preventing rehospitalization during the first year (NNT = 10).
The authors suggest that future studies may yield more meaningful results if participants are stratified using a validated risk stratification system such as the Thrombolysis in Myocardial Infarction score.3 In addition, future studies should include more women and have longer durations. For now, the most current practice guidelines from the American Heart Association Task Force give Level of Evidence A to an early invasive strategy in patients with UA or NSTEMI. The updated guidelines are available at http://www.acc.org/qualityandscience/clinical/guidelines/unstable/unstable.pdf.2
Address correspondence to Nathan Hitzeman, M.D., at hitzemn@sutterhealth.org. Reprints are not available from the author.
Author disclosure: Nothing to disclose.
REFERENCES
1. Hoenig MR, Doust JA, Aroney CN, Scott IA. Early invasive versus conservative strategies for unstable angina and non-ST-elevation myocardial infarction in the stent era. Cochrane Database Syst Rev 2006;(3):CD004815.
2. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Accessed October 25, 2006, at: http://www.acc.org/qualityandscience/clinical/guidelines/unstable/incorporated/index.htm.
3. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 2000;284:835-42.
Cochrane Briefs
Hepatitis B Vaccine for Infants of HBsAg-Positive Mothers
Clinical Question
Do hepatitis B vaccine and immune globulin prevent hepatitis B infection in newborns of mothers who are positive for hepatitis B surface antigen (HBsAg)?
Evidence-Based Answer
Hepatitis B vaccine, hepatis B immune globulin, and the combination of both reduce the risk of transmission of hepatitis B virus from mother to newborn, especially in newborns of mothers positive for hepatitis B e antigen (HBeAg). The combination of vaccine and immune globulin is more effective than vaccine alone.
Practice Pointers
Without intervention, 70 to 90 percent of infants born to women who are positive for both HBsAg and HBeAg will have chronic hepatitis B infection by six months of age.1 This Cochrane review of 29 clinical trials demonstrates that vaccine and immune globulin each are effective in preventing infection and that they are more effective in combination.
The reviewers found that compared with no intervention, hepatitis B immune globulin alone and the combination of immune globulin and vaccine reduced transmission of hepatitis B virus by 50 percent. The combination of vaccine and hepatitis B immune globulin also reduced transmission compared with vaccine alone (relative risk = 0.54; 95% confidence interval [CI], 0.41 to 0.73; 10 trials). Recombinant and plasma-derived vaccines were comparable in effectiveness, as were high-dose and low-dose vaccines.
Most of the trials included only mothers who tested positive for HBsAg and HBeAg. The number needed to treat to prevent transmission of hepatitis B from mothers who are positive for HBsAg but negative for HBeAg is likely to be much lower, but data for this population are limited.
The Advisory Committee on Immunization Practices recommends that all pregnant women be screened for HBsAg during routine prenatal care and that they be reevaluated and the results recorded when they report to the hospital in labor. Patients with positive results should be reported to local or state prenatal hepatitis B prevention programs and case-management tracking programs. Women who present in labor who are at high risk of infection or do not have HBsAg results should be tested as soon as possible. Newborns of mothers who are positive for HBsAg should receive single-antigen hepatitis B vaccine and hepatitis B immune globulin within 12 hours of birth. Thimerosal has been removed from vaccines, so neonatal vaccination can be performed.
Infants of mothers whose HBsAg status is unknown should receive single-antigen hepatitis B vaccine within 12 hours of birth. If the results of subsequent HBsAg testing of the mother are positive, the infant should receive hepatitis B immune globulin within seven days of birth. A complete hepatitis B vaccine series should be completed on all infants regardless of newborn vaccinations. At the end of the vaccination series at nine to 18 months, the infant should be tested for HBsAg and hepatitis B surface antibody.2
Source: Lee C, et al. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst Rev 2006;(2):CD004790.
REFERENCES
1. Wong VC, Ip HM, Reesink HW, Lelie PN, Reerink-Brongers EE, Yeung CY, et al. Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Double-blind randomised placebo-controlled study. Lancet 1984;1:921-6.
2. Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents [Published correction appears in MMWR Morb Mortal Wkly Rep 2006;55:158-9]. MMWR Recomm Rep 2005;54(RR-16):1-23. Accessed October 24, 2006, at: http://www.cdc.gov/MMWR/preview/mmwrhtml/rr5416a1.htm.
Clinical Question
Is humidified air an effective treatment for laryngotracheobronchitis (croup)?
Evidence-Based Answer
Available data do not support a clinically important benefit of humidified air for symptomatic treatment of children with croup. However, it does not appear to be harmful.
Practice Pointers
Although humidified air is recommended routinely to parents of children with croup as a way to relieve symptoms, it has not been studied well. In addition, animal studies have found that airway resistance is reduced more by warm or cool dry air than by warm moist air. The authors of this systematic review searched the literature and identified three studies with a total of 135 patients. The number of participants in each study was between 16 and 71, and the overall age range was three months to six years. All studies compared warm or cool humidified air with no treatment, took place in the emergency department or children's ward, and evaluated outcomes using a validated symptom score. The studies were generally of good quality, although only one had outcomes assessed by researchers blinded to the treatment assignment.
The authors combined symptom scores assessed at 20 to 60 minutes and found no significant benefit with humidified air. Although at 20 to 30 minutes, there was a trend toward benefit with mist; at 60 minutes, the trend favored no treatment (effect sizes = -0.4 [95% confidence interval (CI), -0.82 to 0.02] and 0.2 [95% CI, -0.64 to 1.05], respectively).
There are no standard national guidelines for the management of croup in the United States. A guideline from the Alberta Medical Association does not recommend mist therapy because it has not been shown to be effective,1 and an evidence-based guideline from Monash University in Australia states that mist and humidified air have not been demonstrated to be effective treatments for children with croup.2 Oral dexamethasone (Decadron; 0.6 mg per kg) improves outcomes and reduces the risk of hospital admission. For severe croup with stridor, respiratory distress, or lethargy, blow-by oxygen and nebulized racemic epinephrine 2.25% (0.5 mL in 2.5 mL saline) or L-epinephrine 1:1,000 (0.5 mL) also are treatment options.
Source: Moore M, et al. Humidified air inhalation for treating croup. Cochrane Database Syst Rev 2006;(3):CD002870.
REFERENCES
1. Alberta Clinical Practice Guideline Working Group. Diagnosis and management of croup. Edmonton, Alberta: Alberta Medical Association, 2005. Accessed October 24, 2006, at: http://www.topalbertadoctors.org/TOP/CPG/Croup/Croup.htm.
2. Health for Kids in the South East Croup Guideline Development Group. Evidence-based practice guideline for the management of croup in children. Clayton, Victoria, Australia: Monash Institute of Health Services Research, 2006. Accessed October 24, 2006, at: http://www.mihsr.monash.org/hfk/pdf/hfkcroupguidelinefinalweb.pdf.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). See Clinical Quiz on page 21.
The series coordinator for AFP is Clarissa Kripke, M.D., Department of Family and Community Medicine, University of California, San Francisco.
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