Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study.

BACKGROUND: Aggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. Although observational data have suggested that pretreatment with a high loading dose of clopidogrel may be more effective than a conventional dose, this hypothesis has never been tested in a randomized trial. METHODS AND RESULTS: A total of 255 patients scheduled to undergo percutaneous coronary intervention were randomized to a 600-mg (n=126) or 300-mg (n=129) loading regimen of clopidogrel given 4 to 8 hours before the procedure. Creatine kinase MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after intervention. The primary end point was the 30-day occurrence of death, myocardial infarction (MI), or target vessel revascularization. The primary end point occurred in 4% of patients in the high loading dose versus 12% of those in the conventional loading dose group (P=0.041) and was due entirely to periprocedural MI. Peak values of all markers were significantly lower in patients treated with the 600-mg regimen (P< or =0.038). Safety end points were similar in the 2 arms. At multivariable analysis, the high loading regimen was associated with a 50% risk reduction of MI (OR 0.48, 95% CI 0.15 to 0.97, P=0.044). An incremental benefit was observed in patients randomized to the 600-mg dose who were receiving statins, with an 80% risk reduction. CONCLUSIONS: Pretreatment with a 600-mg loading dose of clopidogrel 4 to 8 hours before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduced periprocedural MI in patients undergoing percutaneous coronary intervention. These results may influence practice patterns with regard to antiplatelet therapy before percutaneous revascularization.

Pretreatment with different loading doses of clopidogrel influences P-selectin levels in patients undergoing percutaneous coronary intervention: results from the ARMYDA-2 (antiplatelet therapy for reduction of myocardial damage during angioplasty) SELECT substudy.

OBJECTIVES: ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) trial demonstrated improved clinical outcome in patients undergoing percutaneous coronary intervention (PCI) pretreated with 600 vs. 300 mg clopidogrel loading dose. ARMYDA-2 SELECT is a prospectively planned subanalysis to investigate the effects of those different loading regimens on P-selectin levels. METHODS: From the ARMYDA-2 population, we investigated a subgroup of 84 patients (41 randomized to a 600 mg and 43 to a 300 mg clopidogrel loading dose given at a mean time of 6 h before PCI), in whom soluble P-selectin levels were measured at baseline (at the time of clopidogrel administration), immediately after the procedure, and after 8 and 24 h. RESULTS: In the overall study population, a significant decrease of P-selectin levels was observed from baseline to intervention (from 91 ± 10 to 53 ± 15 ng/ml; P < 0.001). Baseline P-selectin levels were similar in the two groups, whereas at the time of intervention they were significantly lower in the high-dose arm (50 ± 13 vs. 58 ± 15 ng/ml; P = 0.048). P-selectin values between the two arms were not different at the subsequent determinations. The lowest procedural P-selectin levels were observed in patients of the 600 mg arm who had no postprocedural increase of troponin-I above normal limits (P ≤ 0.040). CONCLUSION: Pretreatment with clopidogrel before PCI decreases peri-procedural P-selectin levels; moreover, a 600 mg clopidogrel loading dose, compared with the 300 mg regimen, is associated with reduction of peri-procedural myocardial damage and significant attenuation of P-selectin levels at the time of intervention. These results may help in identifying mechanisms underlying clinical benefit of the high clopidogrel load in PCI.

Geometry and bone mass in primary hyperparathyroidism assessed by peripheral Quantitative Computed Tomography (pQCT).

PURPOSE: Non-invasive measurement by peripheral quantitative computed tomography (pQCT) of bone geometry, biomechanics, and mineral content in patients (pts) with primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: Total, trabecular and cortical mineral density (totBMD, cortBMD, trab BMD), bone geometrical properties (total area, trabecular area, cortical area, cortical/total area) and cortical thickness as biomechanical parameters, were assessed by pQCT at distal radius in 38 (32 F; 6 M) consecutive patients with PHPT (mean age: 62 yrs; range: 30-77). In a subgroup of 12 patients, bone mineral density (BMD) was also measured by means of dual X-ray absorptiometry (DXA) at the lumbar spine (L2-L4). RESULTS: Serum biochemical characteristics were: iPTH (269+/-214 pg/ml; range: 107-1438, normal: 30-65), Calcium (11.4+/-1.1 mg/dl; range: 10.6-13.5, normal: 8.1-10.4) and Alkaline Phosphatase (398+/- 392 U/L; range:173-1174, normal: 98-279). Compa-red with 87 healthy age-matched subjects, total, trabecular and cortical bone densities were reduced in all patients (TotBMD: 216+/-92 mg/cm(3) vs ctr 342+/-94, -37%, p<0.05; TrabBMD: 93+/-51 mg/cm(3) vs ctr 140+/-54, -34%, p <0.01; CorBMD: 711+/-178 mg/cm(3) vs ctr 802+/-175, -11%, p<0.02), such as cortical thickness (0.143+/-0.02 cm vs ctr 0.157+/-0.03, -9%, p<0.02). Among geometrical parameters, only cortical/total area was significant different in the two groups (0,29 vs 0.31; p<0.04). A strong correlation was found between peripheral trabecular bone density assessed by pQCT and axial bone mineral density measured by DXA at L2-L4 (r=0.80; p<0.01). CONCLUSIONS: pQCT measurements in PHPT showed: 1) osteopoenia in all bone compartments partly related to age and menopause; 2) reduced cortical density and cortical thickness consistent with "cancellization" of the inner cortex and lower ability of bone to absorb loading forces. DXA measurements showed osteopoenia also at the lumbar spine, a site rich in trabecular bone. PQCT allowing selective assessment of true volumetric cortical and trabecular bone density such as bone geometry, is proposable in clinical practice, in order to evaluate presurgical bone "status" and to monitor the response to parathyroidectomy.