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- Use of antiplatelet drugs after cardiac operations. [Journal Article]
- Semin Thorac Cardiovasc Surg 2014; 26(3):223-30.
Unfortunately, venous bypass grafts still have a prominent role in operative coronary revascularization (coronary artery bypass graft [CABG]). Venous grafts develop pathologically occlusive disease that limits the effectiveness of CABG, and antiplatelet drugs following operation may limit this problem. The types and indications of antiplatelet drugs following CABG generate some controversy in the recent literature. This review surveys relevant evidence about the use of antiplatelet drugs following CABG to identify the controversial issues, define appropriate questions, and attempt to provide evidence-based interventions that may be helpful in limiting graft occlusion after CABG. Evidence suggests that, in most CABG patients, dual antiplatelet drugs (aspirin and clopidogrel), given after operation, minimizes early (within 1 year) graft failure and improves intermediate-term outcomes, better than single antiplatelet therapy with aspirin alone. There are gaps in the knowledge base that supports this contention, and future clinical trials will likely augment or alter this recommendation.
- Cilostazol: an antiplatelet agent for the neurointerventionist? [REVIEW]
- J Neurointerv Surg 2014 Dec 19.
Antiplatelet agents are essential for the successful management of patients undergoing a variety of neurointerventional procedures. The most commonly used anti-platelet agents are aspirin, clopidogrel and prasugrel. However, there exist an alternative class of anti-platelet agent that may prove useful for neurointerventionists. In particular a drug called cilostazol may have numerous added advantages above and beyond its antiplatelet effect that may be valuable for our patients. In this short review we aim to highlight some of these potential advantages.
- Efficacy of Change to New P2Y12 Receptor Antagonists in Patients High on Treatment Platelet Reactivity Undergoing Percutaneous Coronary Intervention. [JOURNAL ARTICLE]
- Clin Appl Thromb Hemost 2014 Dec 18.
Selective intensification of platelet inhibition may improve high on treatment platelet reactivity (HPR). We evaluated the efficacy of dual-antiplatelet therapy, including clopidogrel (CPG), compared to new P2Y12-receptor antagonists in patients with HPR undergoing percutaneous coronary intervention, regarding the outcome of composite major adverse cardiac events (MACEs, including death, acute coronary syndrome [ACS], and stent restenosis). The presence of HPR (71 of 181 patients) almost doubled the risk of MACEs. The new antiplatelet agent reduced MACEs (45.8%, 26%, and 16.7% for CPG, prasugrel, and ticagrelor [TGL]; RR 0.36; 0.13-0.98, P = .03, TGL), specifically in patients with ACS. Failure to reduce HPR after the antiplatelet change and diabetes were independent predictors for MACEs. The HPR was early and effectively reduced after changing the antiplatelet therapy, but the intensity of this reduction did not significantly decrease the risk of MACEs. These findings support the benefit of HPR-guided intensification of platelet inhibition. Whether the intensity of this reduction improves the patient's clinical outcomes deserves further investigation.
- Effect of Prasugrel Pre-Treatment Strategy in Patients Undergoing Percutaneous Coronary Intervention for NSTEMI: The ACCOAST-PCI Study. [Journal Article]
- J Am Coll Cardiol 2014 Dec 23; 64(24):2563-71.
After percutaneous coronary intervention (PCI) for non-ST-segment elevation myocardial infarction (NSTEMI), treatment with a P2Y12 antagonist with aspirin is recommended for 1 year.The oral P2Y12 antagonists ticagrelor and prasugrel have higher recommendations than clopidogrel, but it is unknown if administration before the start of PCI is beneficial.In the randomized, double-blind ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction) trial, 4,033 patients were diagnosed with NSTEMI and 68.7% underwent PCI; 1,394 received pre-treatment with prasugrel (30-mg loading dose), and 1,376 received placebo. At the time of PCI, patients who received pre-treatment with prasugrel received an additional 30-mg dose of prasugrel, and those who received placebo received a 60-mg loading dose of prasugrel. Primary efficacy was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout through 7 days from randomization. Investigators captured the presence of thrombus on initial angiography and during PCI.The incidence of the primary endpoint through 7 days from randomization in the pre-treatment group versus the no pre-treatment group was 13.1% versus 13.1% (p = 0.93). Pre-treatment with prasugrel was not associated with decreases in any ischemic event, including total mortality. Patients with thrombus on angiography had a 3-fold higher incidence of the primary endpoint than patients without thrombus. There was no impact of pre-treatment with prasugrel on the presence of thrombus before PCI or on occurrence of stent thrombosis after PCI. There was a 3-fold increase in all non-coronary artery bypass graft Thrombolysis In Myocardial Infarction (TIMI) major bleeding and a 6-fold increase in non-coronary artery bypass graft life-threatening bleeding with pre-treatment with prasugrel; the same trends persisted in patients who had radial or femoral access even with use of a closure device.These findings support deferring treatment with prasugrel until a decision is made about revascularization in patients with NSTEMI undergoing angiography within 48 h of admission. (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction [ACCOAST]; NCT01015287).
- Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats. [JOURNAL ARTICLE]
- J Gastroenterol Hepatol 2014 Dec.:37-46.
We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats.Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L ASA at a rate of 0.4 mL/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate. Clopidogrel (30 mg/kg) was given p.o. 24 h before the perfusion. Rebamipide (3-30 mg/kg) or other antiulcer drugs were given i.d. before the ASA perfusion.Slight gastric bleeding or damage was observed with the perfusion of ASA under the stimulation of acid secretion, whereas these responses were significantly increased in the presence of clopidogrel. Both omeprazole and famotidine inhibited acid secretion and prevented these responses to ASA plus clopidogrel. Rebamipide had no effect on acid secretion, but dose-dependently prevented gastric bleeding in response to ASA plus clopidogrel, with the degree of inhibition being almost equivalent to that of the antisecretory drugs, and the same effects were obtained with the gastroprotective drugs, irsogladine and teprenone. These agents also reduced the severity of gastric lesions, although the effects were less than those of the antisecretory drugs.These results suggest that the antiplatelet drug, clopidogrel, increases gastric bleeding induced by ASA under the stimulation of acid secretion, and the gastroprotective drug, rebamipide, is effective in preventing the gastric bleeding induced under such conditions, similar to antisecretory drugs.
- Bivalirudin for acute coronary syndromes: premises, promises and doubts. [JOURNAL ARTICLE]
- Thromb Haemost 2014 Dec 18; 113(3)
Bivalirudin is a valuable anticoagulant option in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention. Advantages over heparin as a parenteral anticoagulant include more predictable pharmacokinetics and pharmacodynamics, shorter half-life, no need for cofactors, some degree of antiplatelet effect, and the ability to inhibit clot-bound thrombin. Clinical evidence supporting the use of bivalirudin over heparin in current ACS guidelines, however, derives mostly from early randomised trials that may no longer reflect current management patterns, now including the use of oral antiplatelet agents more potent than clopidogrel (i.e. prasugrel or ticagrelor) and a broader implementation of strategies to reduce bleeding (i.e. radial access for percutaneous coronary intervention, and use of glycoprotein IIb/IIIa inhibitors only in bailout situations). Defining the fine balance between bivalirudin efficacy and safety over heparins in the context of other antithrombotic treatments remains a challenge in clinical practice, particularly in a fast-evolving scenario, such as ACS, where numerous new trials have been presented in very recent times. Here we provide an up-to-date overview of the evidence on the use of bivalirudin in ACS, with focus on new data, open issues, and future directions.
- Intraprocedural Thrombus Formation in the Left Main Tract During Primary Percutaneous Coronary Intervention. [JOURNAL ARTICLE]
- J Coll Physicians Surg Pak 2014 Nov; 24(11):S163-S165.
A 67 years old male presented with acute myocardial infarction. Emergency coronary angiography demonstrated subocclusive stenosis in the proximal Left Anterior Descending artery (LAD). Primary Percutaneous Coronary Intervention (PCI) was complicated with intraprocedural thrombosis in the distal Left Main Tract (LMT) following implantation of a stent in the mid LAD. The thrombus was successfully managed with heparin and quadruple antiplatelet therapy (abciximab, aspirin, clopidogrel, and cilostazol) after several attempts of thrombectomy adequate distal flow was achieved. The lesion in the proximal LAD was successfully treated using a kissing stent technique in the second stage.
- [Factors influencing platelet aggregation in patients with acute coronary syndrome]. [English Abstract, Journal Article]
- Ter Arkh 2014; 86(9):83-9.
To study factors influencing platelet aggregation in patients with acute coronary syndrome (ACS).The investigation enrolled 147 patients with ACS. Their blood was sampled on days 1, 3-5, and 8-12 days after the onset of ACS. All the patients received acetylsalicylic acid (ASA) 300 mg on day 1, then 100 mg/day and clopidogrel 300-600 mg on day 1, then 75-150 mg/day. Platelet aggregation was analyzed in 65 patients on day 1 after ASA intake, but prior to clopidogrel therapy. The aggregation was induced by 5 and 20 pmol of ADP.With the use of clopidogrel 75 mg/day on day 3-5, platelet aggregation was reduced by 2.1 and 1.7 times for 5 and 20 μmol of ADP, respectively, as compared to day 1 (ASA without clopidogrel) and remained unchanged on days 8-12. Increasing the dose of clopidogrel up to 150 mg/day potentiated its antiaggregatory effect. On day 1 (ASA without clopidogrel), there was a direct correlation between platelet aggregation levels and mean platelet volume (MPV) (correlation coefficients (r), 0.526 (p < 0.001) and 0.368 (p = 0.015) for 5 and 20 μmol of ADP, and between platelet aggregation levels and glycoprotein (GP) IIb-IIIa (r = 0.387; p = 0.002 and r = 0.411 (p < 0.001) for 5 and 20 μmol of ADP. No similar correlations were found on days 3-5 and 8-12 of administration of ASA and clopidogrel. The genetic polymorphism of GP lIb-Illa (GP Ila Leu33Pro) was not noted to affect platelet aggregation. Examining the effects of genetic variations in cytochrome P450 isoform CYP2C19 (a clopidogrel metabolizer) revealed the enhanced aggregation stimulated with 20 μmol of ADP in the carriers of slowly clopidogrel-metabolizing haplotype of CYP2C19 (differences were found on days 3-5 as compared to rapidly and routinely metabolizing haplotypes).In the patients with ACS, platelet aggregation is influenced by MPV, GP IIb-IIIa levels, and CYP2C19 polymorphism and is not by GP IIb-IIIa polymorphism.
- [Effect of original and generic clopidogrel on prognosis in relation to different gene polymorphisms]. [English Abstract, Journal Article]
- Ter Arkh 2014; 86(9):77-82.
To analyze the influence of clinical and pharmacogenetic factors on the risk of resistance to original or generic clopidogrel and that of cardiovascular events (CVE) during 12 months of follow-up.Two hundred and fifty patients admitted to Moscow hospitals in October 2011 to September 2012 were examined. All the patients received clopidogrel. During their stay at hospital, venous blood samples were collected twice (before and 7-10 days after continuous clopidogrel intake). Platelet function was determined by optical aggregometry. A less than 10% reduction in platelet aggregation was taken as a resistance criterion. In addition, CYP2C9 and CYP2C19 gene polymorphisms were investigated.Whether original or generic clopidogrel is used, the level of baseline or post-7-day ADP-induced platelet aggregation (ADP aggregation) fails to affect the risk of its resistance. Evaluation of ADP-induced platelet aggregation in patients with different CYP2C9 and CYP2C19 gene polymorphisms during the administration of original or generic clopidogrel also showed no significant differences in its resistance. During the 12-month follow-up, CVE significantly less frequently occurred as a result of the intake of original versus generic clopidogrel.The use of original clopidogrel does not affect the risk of resistance to antiplatelet drugs, but it is associated with the lower incidence of CVE during a year.
- [Thromboprophylaxis in patients with coronary aneurysms caused by Kawasaki disease]. [English Abstract, Journal Article]
- Nihon Rinsho 2014 Sep; 72(9):1659-63.
Patients with coronary artery aneurysms caused by Kawasaki disease are at increased risk of coronary thrombosis and ischemia. To prevent coronary thrombosis, long term thromboprophylaxis using anti-platelet drugs, such as aspirin, dipyridamole, ticlopidine, clopidogrel, and abciximab, with or without warfarin is recommended by official guidelines. In fact, aspirin or aspirin with warfarin are the most frequently administered regimen in these patients with coronary aneurysms. However, still there has been paucity of data and no randomized controlled study to determine the efficacy of these drugs. This short article describes the currently accepted practice of thromboprophylaxis in patients with coronary aneurysms caused by Kawasaki disease.