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General Cardiology

both before and after PCI without a significant increase in major or minor bleeding. These data add further support to the early use of clopidogrel in STEMI and the broader strategy of clopidogrel pretreatment in patients undergoing PCI. The PCI-CLARITY study provides important data, and suggests that patients receiving thrombolytic therapy for STEMI should also receive a 300-mg loading dose of clopidogrel followed by 75 mg daily. All patients not receiving a loading dose within several days of angiography should also be considered for clopidogrel retreatment (i.e., repeat loading dose) at the time of PCI. Debabrata Mukherjee

Abstracts Effect of Clopidogrel Pretreatment Before Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction Treated With Fibrinolytics: The PCI-CLARITY Study Sabatine MS, Cannon CP, Gibson CM, et al. for the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)–Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators. JAMA 2005;294:1224 –32.

Effect of Thrombolytic Therapy on the Risk of Cardiac Rupture and Mortality in Older Patients With First Acute Myocardial Infarction

Study Question: To determine whether clopidogrel pretreatment before PCI in patients with recent ST-segment elevation myocardial infarction (STEMI) is superior to clopidogrel treatment initiated at the time of PCI in preventing major adverse cardiovascular events. Methods: The PCI-Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) study was a prospectively planned analysis of the 1863 patients undergoing PCI after mandated angiography. Patients received aspirin and were randomized to receive either clopidogrel (300 mg loading dose, then 75 mg once daily) or placebo initiated with fibrinolysis and given until coronary angiography, which was performed 2 to 8 days after initiation of the study drug. For patients undergoing coronary artery stenting, it was recommended that open-label clopidogrel (including a loading dose) be administered after the diagnostic angiogram. The primary outcome was the incidence of the composite of cardiovascular death, recurrent MI, or stroke from PCI to 30 days after randomization. Secondary outcomes included MI or stroke before PCI and the aforementioned composite from randomization to 30 days. Results: Pretreatment with clopidogrel significantly reduced the incidence of cardiovascular death, MI, or stroke following PCI (34 [3.6%] vs. 58 [6.2%]; adjusted odds ratio [OR], 0.54 [95% CI 0.35– 0.85]; p⫽0.008). Pretreatment with clopidogrel also reduced the incidence of MI or stroke prior to PCI (37 [4.0%] vs. 58 [6.2%]; OR, 0.62 [95% CI 0.40 – 0.95]; p⫽0.03). Overall, pretreatment with clopidogrel resulted in a highly significant reduction in cardiovascular death, MI, or stroke from randomization through 30 days (70 [7.5%] vs. 112 [12.0%]; adjusted OR, 0.59 [95% CI 0.43– 0.81]; p⫽0.001; number needed to treat ⫽ 23). There was no significant excess in the rates of TIMI major or minor bleeding (18 [2.0%] vs. 17 [1.9%]; p⬎0.99). Conclusions: The investigators concluded that clopidogrel pretreatment significantly reduces the incidence of cardiovascular death or ischemic complications both before and after PCI and without a significant increase in major or minor bleeding. Perspective: This study suggests that in high-risk patients with STEMI treated with fibrinolytic therapy, a strategy of clopidogrel pretreatment significantly reduces the incidence of cardiovascular death and ischemic complications

Bueno H, Martı´nez-Sellés M, Pérez-David E, López-Palop R. Eur Heart J 2005;26:1705–11. Study Question: To evaluate the effect of thrombolysis on mortality and its causes in older patients with acute myocardial infarction (AMI). Methods: The population consisted of all patients ⱖ75 years old admitted to the coronary care unit of Hospital General Universitario’ within 24 h from symptom onset with a definite diagnosis of first ST-segment elevation/left bundle branch block myocardial infarction. Clinical outcomes were analyzed according to the type of reperfusion therapy received by the patients. Results: An analysis of 706 consecutive patients ⱖ75 years old with a first AMI showed that although there were important differences in baseline characteristics among patients treated with thrombolysis, primary angioplasty (PA) and those who did not receive reperfusion therapy, 30-day mortality did not differ (29%, 25% and 32%, respectively). The main cause of death in patients treated with thrombolysis was cardiac rupture (54%), whereas most of the other patients died in cardiogenic shock. Patients who received thrombolysis had a higher (p⬍0.0001) incidence of free wall rupture (FWR) (17.1%) compared with those who did not receive reperfusion therapy (7.9%) or who underwent PA (4.9%). By multivariable analysis, patients treated with thrombolytic therapy (TT) showed an excess risk of FWR (OR 3.62; 95% CI 1.79 –7.33), a hazard not observed in patients who underwent PA. When compared with patients who did not receive reperfusion therapy, the OR of 30-day mortality was 1.07 (95% CI 0.65–1.76) for patients treated with thrombolysis and 0.78 (95% CI 0.45–1.34) for those who underwent PA. The figures for 24-month mortality were 0.78 (95% CI 0.65–1.76) and 0.67 (95% CI 0.28 – 0.81), respectively. Conclusions: The investigators concluded that treatment of first AMI with TT increases the risk of FWR in very old patients, a risk not observed in patients treated with PA. Perspective: The study suggests that in elderly patients, treatment of first AMI with thrombolytic therapy increases the risk of FWR, an effect that may attenuate its early

ACC CURRENT JOURNAL REVIEW December 2005

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