Cochrane for Clinicians
Putting Evidence into Practice
Early Invasive Therapy or Conservative Management for Unstable Angina or NSTEMI?
Am Fam Physician. 2007 Jan 1;75(1):47-49.
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.
How effective is early invasive treatment of patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI) compared with conservative management?
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
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.
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 non-fatal 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 SystematicReviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org)
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 email@example.com. Reprints are not available from the author.
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.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Nathan Hitzeman, M.D., presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a critique of the review. The practice recommendations in this activity are available at http://www.cochrane.org/reviews/en/AB004815.html.
The series coordinator for AFP is Clarissa Kripke, M.D., Department of Family and Community Medicine, University of California, San Francisco.
Copyright © 2007 by the American Academy of Family Physicians.
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