Important changes in long-term management
For most primary care physicians—with the possible exception of those in rural areas, who are faced with the burden of emergent care—the most important aspect of the revised guidelines is the changes in recommendations for long-term management of patients with unstable angina and NSTEMI. The goal of these new recommendations is to reduce the risk of subsequent cardiovascular events, such as death, recurrent MI, congestive heart failure, and stroke. Based on the results of the groundbreaking studies reviewed by the ACC/AHA panel, major changes to the original guidelines were necessary for the areas of long-term antiplatelet therapy and risk reduction.
TABLE
ACC/AHA task force classifications on patient evaluation and therapy
| Levels of evidence | ||
|---|---|---|
| A (highest) | B (intermediate) | C (lowest) |
| Data derived from multiple randomized clinical trials involving large numbers of patients. | Data derived from limited number of randomized clinical trials involving small numbers of patients or from analyses of nonrandomized trials or observation registries. | Basis of recommendation from expert opinion. large numbers of patients. |
| Recommendations made were based on expert analyses of published data. | ||
Antiplatelet therapy
Antiplatelet therapy—aspirin, GP IIb/IIIa antagonists, or an ADP-receptor antagonist (eg, clopidogrel)—is critical in the treatment and management of patients with unstable angina/NSTEMI.2 Based on the ACC/AHA Task Force classification (Table), aspirin (81–325 mg) should be initiated as quickly as possible after the condition is recognized, and continued indefinitely (SOR: A).
Clopidogrel (300-mg loading dose followed by 75 mg/d) should be administered to patients unable to take aspirin (SOR: A). In addition, clopidogrel 75 mg (once daily) should be added to aspirin therapy as quickly as possible and continued for up to 9 months in patients for whom an early noninterventional approach is planned (SOR: A), or for patients with a planned PCI who are not at high risk of bleeding (SOR: B).2
The CURE trial: clopidogrel and aspirin
The principal studies underlying the new recommendations for long-term antiplatelet therapy are the CURE trial6 and the PCI-CURE7 subset analysis. In the CURE trial, 12,562 patients who presented with unstable angina/NSTEMI within 24 hours following the onset of symptoms were randomized to receive clopidogrel (loading dose of 300 mg followed by 75 mg/d) with aspirin or placebo with aspirin for 3 to 12 months (mean follow-up, 9 months).
The relative risk (RR) of the primary composite outcome including incidence of cardiovascular death, nonfatal MI, or stroke was lower by 20% (RR=0.80; 95% confidence interval [CI], 0.72–0.90; P<.001) in the clopidogrel arm. Similarly, a composite outcome also including revascularization was lower by 14% (RR=0.86; P<.001) for those who received clopidogrel. Benefits were seen in all risk groups. A significant increase in bleeding events was observed in the group that received clopidogrel plus aspirin compared with aspirin alone (major bleeding, P=.001; minor bleeding, P<.001).6
CURE patients were followed for up to 1 year, with a mean follow-up period of 9 months. In addition to the early benefits seen, from day 31 up to 1 year there was a highly significant incremental reduction of 18% in the primary outcome (P<.001) with clopidogrel.7
The PCI-CURE subset: Percutaneous coronary interventions
In the PCI-CURE trial, a subset of patients recruited for CURE who underwent PCI was pretreated with aspirin 325 mg and clopidogrel 75 mg for a median of 10 days. These patients received either clopidogrel or ticlopidine for 4 weeks, and then were restarted on either clopidogrel 75 mg (80%) or placebo in addition to aspirin for an additional mean of 8 months with up to 1 year of follow-up.
Long-term administration of clopidogrel 75 mg following PCI resulted in a 30% reduction (RR=0.70; 95% CI, 0.50–0.70; P=.03) in cardiovascular death, MI, and any revascularization, with a 31% reduction in cardiovascular death or MI (P=.002) compared with placebo. Major bleeding rates were similar between groups (P=.64).9
The CREDO study
The new guidelines for long-term antiplatelet therapy are further supported by the subsequently published Clopidogrel for the Reduction of Events During Observation (CREDO) study.10 CREDO demonstrated a 26.9% relative risk reduction in the combined risk of death, MI, or stroke (95% CI, 3.9%–44.4%; P=.02) in patients with long-term (12 months) aspirin plus clopidogrel 75 mg therapy compared with aspirin plus placebo in 2116 patients undergoing elective PCI or deemed at high likelihood of undergoing PCI. There was no significant increase in the risk of major bleeding (P=.07) between the placebo and clopidogrel arms.
Risk reduction
The revised guidelines also included updated recommendations for risk reduction. It is now recommended that a fibrate or niacin be administered if the HDL cholesterol level is <40 mg/dL (SOR: B).2 Further, statins and a heart-healthy diet should be started during admission and continued after discharge for patients with LDL cholesterol >100 mg/dL (SOR: B).2