Outcome of acute ST-segment elevation myocardial infarction in diabetics treated with fibrinolytic or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: lessons from the GUSTO V trial.

OBJECTIVES: We studied the outcome of diabetics enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) V trial to assess whether the combination of half-dose reteplase and abciximab provides any propitious benefits over standard fibrinolytic therapy in diabetic patients. BACKGROUND: Diabetics with acute ST-segment elevation myocardial infarction (MI) have a worse outcome compared with nondiabetics. Higher-risk patients are usually more likely to benefit from advances in medical therapy. METHODS: We analyzed diabetic patients enrolled in the GUSTO V trial to assess the outcome of those randomized to the combination of half-dose reteplase and abciximab versus those randomized to reteplase. We also evaluated whether any differences existed in presentation and outcome of MI among the diabetics versus the nondiabetics enrolled in the study. RESULTS: The trial enrolled 13782 nondiabetics and 2633 diabetics. Compared to nondiabetics, diabetics had a significantly higher mortality at 30 days (8.5% vs. 5.1%, p < 0.001) and at 1 year (12.7% vs. 7.5%, p < 0.001). Among the diabetic subset, no significant difference existed in the incidence of 30-day (8.8% vs. 8.2%, p = 0.52) or 1-year mortality (13.0% vs. 12.4%, p = 0.62) among patients randomized to reteplase compared to those receiving combination of abciximab and reteplase. The incidence of reinfarction (2.5% vs. 4.3%, p = 0.013), recurrent ischemia (11.8% vs. 14.9%, p = 0.017), and urgent revascularization (10.9% vs. 13.3%, p = 0.055) at seven days was lower in diabetics treated with the combination therapy. CONCLUSIONS: Compared to nondiabetics, diabetics continue to have a worse outcome with MI. Although combination therapy did not provide a survival benefit, nonfatal ischemic outcomes, including reinfarction, recurrent ischemia, and urgent revascularization, were substantially reduced.

Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial.

CONTEXT: Among patients with acute myocardial infarction, combination reperfusion therapy with a platelet glycoprotein IIb/IIIa receptor inhibitor (abciximab) and a half dose of a plasminogen activator (reteplase) did not significantly reduce mortality at 30 days compared with a full dose of reteplase. Rates of nonfatal ischemic complications were significantly diminished. OBJECTIVE: To determine if the beneficial effects of abciximab and reteplase (combination therapy) on early nonfatal complications would translate into a reduction in the risk of death by 1 year. DESIGN, SETTING, AND PATIENTS: One-year follow-up of a randomized controlled trial (Global Use of Strategies To Open Coronary Arteries [GUSTO] V). Of 16 588 patients who had been treated in 820 community and referral hospitals in 20 countries between July 1999 and February 2001, mortality data were available for 16 453 (99.2%). INTERVENTION: Patients were randomly assigned to receive (intravenously) a standard dose of reteplase (two 10-U boluses, 30 minutes apart) or the combination of a standard dose of abciximab (0.25 mg/kg bolus, 0.125 microg/kg per minute infusion [maximum 10 micro g/min for 12 hours]) and a half dose of reteplase (two 5-U boluses, 30 minutes apart). MAIN OUTCOME MEASURE: One-year all-cause mortality rates. RESULTS: All-cause mortality at 1 year occurred in 692 (8.38%) of 8260 patients in the reteplase group and 698 (8.38%) of the 8328 patients in the combination therapy group (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.90-1.11; P>.99). Reinfarction within the first 7 days occurred in 3.5% of patients in the reteplase group and 2.3% of patients in the combination therapy group, and was significantly associated with 1-year mortality (22.6% in patients with reinfarction vs 8.0% in patients without reinfarction; HR, 3.08; 95% CI, 2.53-3.75; P<.001). However, treatment assignment did not significantly influence time of mortality regardless of reinfarction status. CONCLUSION: Combination therapy (abciximab and reteplase) did not reduce mortality over 1 year compared with fibrinolytic therapy with reteplase alone.

Assessing the effect of publication of clinical guidelines on the management of unstable angina and non-ST elevation myocardial infarction in the TIMI III (1990-1993) and the GUARANTEE (1995-1996) Registries.

BACKGROUND: The clinical guidelines for unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) published in 1994 by the Agency for Health Care Policy Research (AHCPR) were intended to help improve treatment. No large study, however, has evaluated the effect of the guidelines on clinical practice METHODS: We compared the treatment of 3,318 patients admitted with UA/NSTEMI in the preguideline Thrombolysis in Myocardial Infarction (TIMI) III Registry (1990-1993) and 2,948 patients enrolled in the postguideline Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry (1995-1996). RESULTS: More patients in GUARANTEE received guideline-recommended medication than did those in TIMI III, specifically beta-blockers (50.9% vs. 40.7%, P < 0.001), heparin (63.3% versus 57.5%, P < 0.001), and the combination of aspirin, heparin, and beta-blockers on admission plus aspirin at discharge (26.9% vs. 18.8%, P < 0.001). These changes were similar in all subgroups, but the greatest improvement in medication use was seen in patients admitted to a tertiary care hospital and in those with a final diagnosis of NSTEMI, i.e., with positive cardiac markers. Conversely, fewer patients in GUARANTEE who fulfilled AHCPR criteria for catheterization underwent the procedure (62.3% in GUARANTEE tertiary centers vs. 44.6% in GUARANTEE nontertiary centers vs. 66.0% in TIMI, P < 0.001). CONCLUSION: After publication of clinical guidelines for UA/NSTEMI, more patients received appropriate pharmacologic treatment, but a significant number of patients remained under-treated. Efforts to improve compliance with guideline recommendations via education and critical pathways are warranted, especially in nontertiary care settings.