Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome.

BACKGROUND: Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES: We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS: The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS: The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.

Outcomes of Percutaneous Intervention in Patients With Takayasu Arteritis.

BACKGROUND: The status of vascular lesion treatment using percutaneous intervention (PI) in Takayasu arteritis (TAK) remains unresolved. OBJECTIVES: This study sought to develop PI strategies appropriate for TAK. METHODS: A prospectively maintained single-center database of TAK PI procedures from 1996 to 2022 was analyzed retrospectively. Obstructive lesions were treated by elective stenting (using bare or covered stents), balloon angioplasty (BA), or cutting-balloon angioplasty (CBA), with adjunctive stenting for suboptimal BA or CBA results. PIs were repeated in restenotic lesions until sustained success was obtained. Aortic or peripheral aneurysms and spontaneous aortic dissections were treated with covered stents or endografts. Immunosuppressive therapy, started before PI, was continued long term. RESULTS: A total of 942 patients underwent PI to treat 2,450 arterial lesions (2,365 stenoses or occlusions, 85 aneurysms or dissections) in 630 subclavian or axillary, 586 renal, 463 aortic, 333 carotid, 188 mesenteric, 116 iliac, 71 coronary, and 63 other arteries; 3,805 PIs were performed (1.55 PIs per lesion; range 1-7 PIs per lesion). Early success was obtained in 2,262 (92.3%), and late success in 1,460 (84.5%) of 1,727 lesions with a median of 39 months (IQR: 15-85 months) of follow-up. Repeated PIs increased late success in obstructive lesions from 48.6% to 83.3%. A total of 1,687 elective stenting lesions achieved 88% late success with 1.49 PIs per lesion; covered stents (1.18 PIs per lesion) restenosed less than bare stents (1.51 PIs per lesion; P < 0.001). A total of 183 (36%) of 513 BA-treated lesions had good outcomes without adjunctive stenting; 122 CBA-treated lesions had 19% dissections and 8% ruptures or pseudoaneurysm formations. Aneurysms or dissections had 91.3% late success after PI. A total of 472 complications occurred in 415 (17%) lesions; 375 (79%) were resolved. CONCLUSIONS: Most vascular lesions in TAK can be effectively, safely, and durably treated using predominantly stent-based PI strategies.