Effect of high bolus dose tirofiban on the inflammatory response following percutaneous coronary intervention.

BACKGROUND: Tirofiban at the bolus dose of 10 microg/kg does not suppress the inflammatory response following percutaneous coronary intervention (PCI). This may be due to less than optimal inhibition of platelet aggregation. High bolus dose tirofiban (25 microg/kg) allows better inhibition of platelet aggregation but its anti-inflammatory effect remains unknown. HYPOTHESIS: High bolus dose tirofiban exhibits anti-inflammatory activity. METHODS: A total of 100 patients referred for PCI were randomized to receive high bolus dose tirofiban followed by a 24-h infusion or a bolus and an infusion of saline. Patients with elevated troponin or with thrombus in the culprit lesion were excluded. Inflammatory markers were measured at baseline and at 24 h. RESULTS: Levels of soluble CD40 ligand (sCD40L) were not affected by PCI while those of interleukin-6 (IL-6) and of high sensitivity C-reactive protein (hs-CRP) significantly increased. Despite inhibiting platelet's aggregation by > 90%, tirofiban did not suppress the rise of IL-6 and hs-CRP. Median (interquartile range) elevation of IL-6 was 0.6 pg/mL (-1.5-3.6) versus 0.4 pg/mL (-0.7-1.8) and that of hs-CRP was 2.1 mg/L (0.7-5.2) versus 2.4 mg/L (1-4.7) in the tirofiban and the control groups, respectively (p = ns). However, in patients with diabetes mellitus, tirofiban significantly suppressed the rise of hs-CRP by 65% (p = 0.01), but did not significantly affect the rise of IL-6. CONCLUSION: In low-risk patients undergoing PCI, tirofiban did not attenuate the rise of inflammatory markers. However, the significant effect in diabetics suggests that tirofiban may have anti-inflammatory activity in higher risk patients.

Effects of clopidogrel on soluble CD40 ligand and on high-sensitivity C-reactive protein in patients with stable coronary artery disease.

BACKGROUND: Antiplatelet therapy with clopidogrel decreases ischemic complication especially in patients with acute coronary syndromes or after percutaneous coronary interventions. Our study was designed to test the effects of clopidogrel on soluble CD40 ligand (sCD40l) and on high-sensitivity C-reactive protein (hs-CRP) in patients with stable coronary artery disease (CAD). METHODS: This is a randomized, double-blind, placebo-controlled study. A total of 73 patients with stable CAD for > 6 months were randomized to receive either clopidogrel (loading dose 300 mg followed by 75 mg/d) for 8 weeks or placebo. Soluble CD40 ligand and hs-CRP were measured at baseline and at completion of the study. RESULTS: All patients were on aspirin therapy, and 74% were on statins. Median and interquartile ranges (IQR) of sCD40l decreased from 64 pg/mL (43-99) at baseline to 53 pg/mL (35-77) at 8 weeks (P = .03) in the clopidogrel group and remained unchanged in the placebo group (59 pg/mL, IQR 35-77 vs 55 pg/mL, IQR 35-78) (P = non significant). Levels of hs-CRP were not affected by therapy and remained unchanged in both groups. CONCLUSIONS: In patients with stable CAD, clopidogrel inhibits the release of sCD40l by platelets, which may contribute to the clinical benefit provided by this drug. This, however, does not translate in a reduction of subclinical inflammation, as measured by hs-CRP.

[Coronary angioplasty for primary cardiogenic shock following acute myocardial infarction]. / L'angioplastie à la phase aiguë de l'infarctus du myocarde compliqué d'un choc cardiogénique primaire.

BACKGROUND: In the setting of acute myocardial infarction (AMI), several investigators have demonstrated that emergency coronary angioplasty (PTCA) reduces in-hospital mortality of primary cardiogenic shock (CS) from 90% to less than 50% ; however, few studies have focused on the current outcome of non selected patients in whom the onset of AMI is immediately complicated by CS. PURPOSE OF THE STUDY: To evaluate in-hospital mortality of the patients admitted to our institution for Q wave AMI presented in CS. MATERIAL AND METHOD: Between 05/93 and 05/03, 30 consecutive pts, 26 men and 4 women, in CS following AMI were treated with direct PTCA, 26 without thrombolysis and 4 as rescue after failed streptokinase. AMI was defined by prolonged chest pain and > or =1 mm ST segment elevation in > or =2 contiguous peripheral leads or > or =2 mm for precordial leads on the admission ECG. The diagnosis of CS was based on the combination of systolic blood pressure of <90 mm Hg, unresponsive to volume expansion, signs of acute circulatory failure (cyanosis, cold extremities, restlessness, mental confusion or coma) and congestive heart failure secondary to myocardial dysfunction. In 40% of cases the diagnosis of CS was only clinical and in 60% of cases was confirmed by a Swan Ganz catheter. Mean age was 62.3 +/- 12.3 years, 7 had triple vessel disease, 14 a double vessel disease, 8 a single vessel disease and in one case a left main disease. The AMI was anterior in 22 pts (73%), inferior in 8 (27%). Intraaortic balloon was used in 3 pts, CPR in 16 (47%), transitory pacemaker in 1 pt, inotropes in 25 pts, emergency coronary artery bypass grafting (CABG) in 1 pt. RESULTS: Success for PTCA with a residual stenosis < 50% and a TIMI flow III was obtained in 26 pts (87%). Mean time between CS and revascularization was 219 +/- 302 minutes. 19 pts (63%) survived and 11 pts (37%) died while at the hospital, 6 from intractable shock, 4 from multiple organ failure and in 1 case from pulmonary hemorrhage. Mean time of revascularization for the surviving was 190 +/- 329 min, and for the dead 295 +/- 212 min. Hospital mortality for inferior infarction is 12.5% after successful angioplasty. Comparison of surviving and non surviving number of patients according to revascularization time showed a significant difference of these groups whether the revascularization was accomplished before or after 120 minutes. [table: see text] CONCLUSION: Direct PTCA for AMI immediately complicated by CS, can be achieved with a high success rate, and can significantly reduce in-hospital mortality; this improvement of survival is most evident if revascularizarion is performed early.