Unstable angina / non ST elevation myocardial infarction initial conservative versus initial invasive strategies


 * Associate Editor-In-Chief: Smita Kohli, M.D.

Overview of Initial Conservative versus Initial Invasive Strategies in Unstable angina/NSTEMI
Two approaches to the use of cardiac catheterization and revascularization in UA/NSTEMI include:
 * An initial invasive strategy, involving routine early cardiac catheterization and revascularization with percutaneous coronary intervention (PCI) or coronary bypass grafting (CABG).
 * The second one is a more conservative approach with initial medical management with catheterization and revascularization only for recurrent ischemia either at rest or on a noninvasive stress test.

The objective of this is to provide a strategy that has the most potential to yield the best clinical outcome and improve long-term prognosis.

Trials supporting Initial Invasive Strategy
More recently conducted randomized trials have shown benefit of early invasive strategy.
 * FRISC II was a prospective randomized multicenter study conducted in 58 Scandinivian hospitals involving of 2457 patients with unstable angina. Patients were assigned in an early invasive or non-invasive treatment strategy with placebo-controlled long-term low-molecular-mass heparin (dalteparin) for 3 months. Coronary angiography was done within the first 7 days in 96% and 10%, and revascularization within the first 10 days in 71% and 9% of patients in the invasive and non-invasive groups, respectively. Patients were followed up at 6 months for composite endpoint of death or myocardial infarction. There was a significant decrease in myocardial infarction alone and non-significant reduction in mortality, independent of dalteparin treatment. Additional analyses showed greater benefit of the invasive strategy in higher risk groups identified by ST segment depression on the admission ECG or troponin elevation.


 * TACTICS-TIMI 18 trial enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. During follow up, the rate of death, MI, or rehospitalization for ACS at 6 months fell from 19.4 percent in the conservative group to 15.9 percent in the early invasive group. Death or nonfatal MI was significantly reduced at 30 days and at 6 months. Using the TIMI risk score, there was significant benefit of the early invasive strategy in intermediate(score 3 to 4) and high-risk patients (5 to 7); whereas low-risk (0 to 2) patients had similar outcomes when managed with either strategy. Interestingly, this study also showed that invasive approach was cost effective as well.


 * The Randomized Intervention Trial of Unstable Angina (RITA-3 trial), a randomised multicentre trial of 1810 patients with non-ST-elevation acute coronary syndromes, an interventional strategy was found to be beneficial when compared to a conservative strategy, mainly because of the halving of refractory or severe angina, and with no increased risk of death or myocardial infarction.


 * ISAR-COOL trial also demonstrated benefit of early intervention. In this study, patients with UA/NSTEMI were randomly allocated to antithrombotic pretreatment for 3 to 5 days or to early intervention after pretreatment for less than 6 hours. Both groups received antithrombotic pretreatment with intravenous unfractionated heparin, aspirin, oral clopidogrel, and intravenous tirofiban. Patients were followed for composite 30-day incidence of large nonfatal myocardial infarction or death from any cause. The study concluded that in patients with unstable angina, deferral of intervention for prolonged antithrombotic pretreatment does not improve the outcome compared with immediate intervention accompanied by intense antiplatelet treatment.


 * A meta-analysis of seven randomized trials by Bavry et al also concluded that in the management of non ST elevation MI, an early invasive strategy improves long term survival and reduces late myocardial infarction and rehospitalization for unstable angina.

Trials supporting Initial Conservative Strategy

 * TIMI IIIB trial studied 1473 patients with unstable angina or non q wave MI were assigned to either tPA versus placebo and early invasive strategy versus conservative approach. The end point for the comparison of the two strategies (death, myocardial infarction, or an unsatisfactory symptom-limited exercise stress test at 6 weeks) occurred in 18.1% of patients assigned to the early conservative strategy and 16.2% of patients assigned to the early invasive strategy (P = NS). It concluded that both strategies can be used to achieve similar low mortality at the end of 6 weeks. However, it did show reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs in early invasive strategy group.


 * VANQWISH trial randomly assigned 920 patients to either invasive management or conservative management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia, within 72 hours of the onset of a non q wave MI. Overall mortality during follow-up(one month and one year) did not differ significantly between patients assigned to the conservative-strategy group and those assigned to the invasive-strategy group.

Indications

 * Initial Invasive strategy:
 * Based on multiple randomized trials, an early invasive strategy is now recommended in patients with UA/NSTEMI with ST segment changes and/or positive troponin on admission or that evolves over the next 24 hours.
 * Some patients may also require urgent catheterization and revascularization in the absence of ST deviation because of ongoing ischemic symptoms or hemodynamic or rhythm instability. Such patients are not candidates for conservative strategy.
 * In patients with other high-risk indicators, such as recurrent ischemia or evidence of congestive heart failure, cardiogenic shock, prior PCI within past 6 months and prior CABG; an early invasive approach is indicated.


 * Initial Conservative strategy:
 * Patients for whom a conservative approach is chosen should undergo a stress test(e.g., exercise or pharmacological stress) for the assessment of ischemia is recommended before discharge or shortly thereafter to identify patients who may also benefit from revascularization. Hence, a plan for noninvasive evaluation is required to detect severe ischemia that occurs spontaneously or at a low threshold of stress and to promptly refer these patients for coronary angiography and revascularization when possible.
 * Also, early assessment of left ventricular function is recommended with an echocardiogram.
 * In recent times, the use of aggressive anticoagulant and antiplatelet agents has reduced the incidence of adverse outcomes in patients managed conservatively.

Timing of an Invasive Strategy
There has been an ongoing debate about what should be the timing for an invasive strategy, once it is decided that the patient will be managed with this strategy.
 * Based on previous trials, patients treated with an invasive strategy generally undergo coronary angiography as early as 2 hrs to as late as 48hrs of admission with variable outcomes.
 * However, based on the recent trial results, it is reasonable for high risk patients to undergo early invasive strategy within 12-24 hours of admission.
 * Recent 2009 update of PCI guidelines by ACC/AHA was based on a large multicenter randomized trial by the TIMACS investigators . This trial randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization). The primary outcome was the composite of death, MI, or stroke at 6 months, and a prespecified secondary outcome was death, MI, or refractory ischemia. Coronary angiography was performed at a median of 14 hours in the early-intervention group and 50 hours in the delayed intervention group. At 6 months, 9.7% of patients in the early-intervention group experienced a primary outcome versus 11.4% in the delayed-intervention group. Death, MI, or refractory ischemia was reduced by 28% in favor of early intervention. Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk but not in the two thirds at low-to-intermediate risk. Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients(GRACE risk score greater than 140).
 * In patients without ST-segment elevation on the electrocardiogram, urgent angioplasty may occur anytime within the first 24 hours according to the ABOARD randomized controlled trial.

==ACC / AHA Guidelines for Initial Conservative versus Initial Invasive Strategy (DO NOT EDIT) ==

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Class I
1. An early invasive strategy (i.e., diagnostic coronary angiography with intent to perform percutaneous coronary revascularization or CABG) is indicated in UA / NSTEMI patients who have refractory angina or hemodynamic or electrical instability (without serious comorbidities or contraindications to such procedures). (Level of Evidence: B)

2. An early invasive strategy (i.e., diagnostic angiography with intent to perform percutaneous coronary revascularization or CABG) is indicated in initially stabilized UA / NSTEMI patients (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events (Level of Evidence: A)

Class IIa
1. It is reasonable to choose an early invasive strategy (within 12 to 24 hours of admission) over a delayed invasive strategy for initially stabilized high-risk patients with UA / NSTEMI. For patients not at high risk, a delayed invasive approach is also reasonable. (Level of Evidence: B)

Class IIb
1. In initially stabilized patients:


 * a. An initially conservative (i.e., a selectively invasive) strategy may be considered as a treatment strategy for UA / NSTEMI patients (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events including those who are troponin positive. (Level of Evidence: B)
 * b. The decision to implement an initial conservative (vs. initial invasive) strategy in these patients may be made by considering physician and patient preference. (Level of Evidence: C)

2. An invasive strategy may be reasonable in patients with chronic renal insufficiency. (Level of Evidence: C)

Class III
1. An early invasive strategy (i.e., diagnostic angiography with intent to perform coronary artery revascularization) is not recommended in patients with extensive comorbidities (e.g., liver failure or pulmonary failure, cancer), in whom the risks of revascularization and comorbid conditions are likely to outweigh the benefits of revascularization. (Level of Evidence: C)

2. An early invasive strategy (i.e., diagnostic angiography with intent to perform coronary artery revascularization) is not recommended in patients with acute chest pain and a low likelihood of Acute coronary syndromes. (Level of Evidence: C)

3. An early invasive strategy (i.e., diagnostic angiography with intent to perform coronary artery revascularization) should not be performed in patients who will not consent to revascularization regardless of the findings. (Level of Evidence: C)}}

==ACC/AHA Guidelines for the Timing of Angiography and Antiplatelet Therapy in UA/NSTEMI(DO NOT EDIT) ==

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Class I
1. Patients with definite or likely UA/NSTEMI selected for an invasive approach should receive dual-antiplatelet therapy (Level of Evidence: A). Aspirin should be initiated on presentation (Level of Evidence: A), clopidogrel (before or at the time of PCI) (Level of Evidence: A) or prasugrel (at the time of PCI) (Level of Evidence: B) is recommended as a second antiplatelet agent.

Class IIa
1. It is reasonable for initially stabilized high-risk patients with UA/NSTEMI (GRACE i.e. Global Registry of Acute Coronary Events, risk score greater than 140) to undergo an early invasive strategy within 12 to 24 hours of admission. For patients not at high risk, an early invasive approach is also reasonable. (Level of Evidence: B)}}