Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease.

BACKGROUND: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown. METHODS: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. RESULTS: Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88-1.15; P=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86-1.15; P=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78-1.36; P=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months. CONCLUSIONS: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01732822.

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study.

AIMS: Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS. METHODS AND RESULTS: We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). CONCLUSION: A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

Clinical evidence for oral antiplatelet therapy in acute coronary syndromes.

Platelet-mediated thrombosis is a major pathophysiological mechanism that underlies acute coronary syndromes, and therefore, antiplatelet therapy is an important foundation in the treatment and prevention of recurrence of these syndromes. Nearly 30 years ago, aspirin was the first agent to show a benefit for acute coronary syndromes and is still a key therapeutic agent. The landmark CURE trial showed that the addition of a P2Y12 antagonist, clopidogrel, to aspirin was beneficial in the treatment of acute coronary syndromes. Despite substantial benefits with clopidogrel, limitations include the slow speed of onset, variable response, and a modest antiplatelet effect. Next-generation P2Y12 antagonists, prasugrel and ticagrelor, overcome these limitations and have been shown, in large-scale clinical trials for acute coronary syndromes, to reduce ischaemic events more than clopidogrel, at the expense of an increase in bleeding. Additional agents that target platelets by alternate mechanisms, including the protease-activated receptor-1 antagonist vorapaxar, have shown ischaemic benefit. These large-scale trials inform treatment decisions that need to balance ischaemic benefit and bleeding risk in patients with acute coronary syndromes. This Series paper describes major trial results, implications for clinical practice, and summarises continuing controversy.

Design and rationale for the Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial.

BACKGROUND: Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD, whereas clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events. STUDY DESIGN: EUCLID is a randomized, double-blind, parallel-group, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD. Subjects with established PAD will be randomized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. The primary end point is a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Other end points address limb events including acute leg ischemia, need for revascularization, disease progression by ankle-brachial index, and quality of life. The primary safety objective is Thrombolysis in Myocardial Infarction-defined major bleeding. Recruitment began in December 2012 and was completed in March 2014; 13,887 patients were randomized. The trial will continue until at least 1,364 adjudicated primary end points occur. CONCLUSIONS: The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel, given as antiplatelet monotherapy, will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD.

Safety of 6-month duration of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndromes: Rationale and design of the Smart Angioplasty Research Team-safety of 6-month duration of Dual Antiplatelet Therapy after percutaneous coronary intervention in patients with acute coronary syndromes (SMART-DATE) prospective multicenter randomized trial.

BACKGROUND AND RATIONALE: Dual antiplatelet therapy (DAPT) is a fundamental treatment that optimizes clinical outcomes after percutaneous coronary intervention, especially in patients with acute coronary syndrome (ACS). Although current international guidelines recommend DAPT for at least 12 months after implantation of a drug-eluting stent in patients with ACS, these recommendations are not based on randomized controlled trials dedicated to ACS population. STUDY DESIGN: The SMART-DATE trial is a prospective, multicenter, randomized, and open-label study to demonstrate the noninferiority of 6-month DAPT compared with 12 months or longer DAPT in patients with ACS undergoing percutaneous coronary intervention. A total of 2,700 patients will undergo prospective, random assignment to either of the DAPT duration groups. To minimize the bias from different stent devices, the type of stents will be randomly assigned (everolimus-eluting stents, zotarolimus-eluting stents, or biolimus A9-eluting stents). The primary end point is a composite of all-cause death, myocardial infarction, and cerebrovascular events at 18 months after the index procedure. The major secondary end points are definite/probable stent thrombosis defined by the Academic Research Consortium and bleeding defined by Bleeding Academic Research Consortium type 2-5. CONCLUSIONS: The SMART-DATE randomized trial is the first study exploring the safety of 6-month DAPT compared with conventional 12-month or longer DAPT dedicated to patients with ACS after second-generation drug-eluting stent implantation.

Effect of long-term adherence to clopidogrel on the VASP-PRI after elective coronary stent implantation: a randomized controlled study.

AIMS: The biological response to clopidogrel is highly variable and a poor responsiveness is associated with major adverse cardiac events. Adherence to therapy is a major cause of poor responsiveness but its impact on long-term platelet inhibition is unknown. The objective of the present study was to evaluate the effect of different programmes monitoring adherence to clopidogrel on platelet reactivity. METHODS: The study took the form of a monocentric, parallel group, randomized controlled trial. Adults treated with clopidogrel 75 mg after elective coronary stenting were randomized into one of three groups: (i) a standard of care group; (ii) a standard of care + adherence electronic monitoring group, in which drug intake was recorded but kept blinded until the study end; or (iii) an integrated care group, with regular feedback on recorded adherence. Clopidogrel response was assessed with the vasodilator-stimulated phosphoprotein-platelet reactivity index (VASP-PRI) at randomization, 3 months and 6 months. RESULTS: A total of 123 adults were enrolled and randomized. Baseline VASP-PRI was highly variable, with a mean of 48 ± 18.8%. No difference between groups in VASP-PRI was found at 6 months (P = 0.761), despite better adherence to clopidogrel in the integrated care group. However, adherence (P = 0.035) and baseline VASP-PRI (P = 0.015) were associated with VASP-PRI at 3 months and 6 months. The association between adherence and VASP-PRI was lost in patients with baseline VASP-PRI > 50%. Diabetes, CYP2C19*2 carrier status and body mass index were significant predictors of VASP-PRI. CONCLUSIONS: The platelet response to clopidogrel during chronic therapy remained highly variable, despite high adherence. Different adherence monitoring programmes did not affect VASP-PRI at 6 months. Poor adherence is associated with lower VASP-PRI only in initial good responders to clopidogrel.

[Budget impact analysis of antiplatelet therapy with ticagrelor and clopidogrel in patients with acute coronary syndrome after coronary artery bypass surgery]. / Analiz «vliyaniya na byudzhet¼ primeneniya antitrombotsitarnoi terapii tikagrelorom i klopidogrelom u patsientov s ostrym koronarnym sindromom, perenesshikh operatsiyu koronarnogo shuntirovaniya.

AIM: Clinical and economic examinations were made to study whether it is appropriate to use antiplatelet therapy (APT) with ticagrelor in combination with acetylsalicylic acid (ASA) versus a combination of clopidogrel and ASA in patients with acute coronary syndrome (ACS) following coronary artery bypass surgery (CABS). MATERIAL AND METHODS: A budget impact analysis was used. Data on the efficiency and safety of APT were taken from a relevant analysis in the subgroups of the randomized controlled trial PLATO. Direct medical cost due to APT and expenses on therapy for acute myocardial infarction, stroke, and massive bleeding, and those on medical care for patients dying from cardiovascular events and other causes, as well as indirect cost - gross domestic product (GDP) losses due to untimely death, were taken into account. The findings were assessed from the perspectives of society. RESULTS: The analysis indicated that direct medical costs per patient following CABS, both in case of calculation based on the recorded price for ticagrelor and on the median registered prices for clopidogrel generics, and based on the auction prices for comparison agents proved to be lower when clopidogrel was administered because of the higher cost of ticagrelor-based APT. At the same time GDP losses due to untimely death, as calculated per patient with ACS during post-CABS therapy with clopidogrel + ASA, were more than twice above average losses per patient taking ticagrelor in combination with ACA (107,122 and 221,645 rubles, respectively). From the registered price for ticagrelor and the median registered prices for clopidogrel generics, the total costs per patient with ACS following CABS were lower if Brilinta was used in combination with ASA versus therapy with clopidogrel in combination with ASA (210,092 and 273,257 rubles per year, respectively; the cost savings were 63,165 rubles per patient per year when ticagrelor was administered). On the basis of the auction prices for comparison drugs, the total costs per patient with ACS after CABS proved to be lower if Brilinta was used in combination with ASA versus therapy with brand name clopidogrel in combination with ASA (201,018 and 293,982 rubles per patients year, respectively; the cost savings were 92,963 rubles per patient per year when ticagrelor was used). CONCLUSION: The use of ticagrelor in combination with ASA ensures resource savings to treat ACS patients undergoing CABS as compared with a regiment including a combination of clopidogrel and ASA.

Early P2Y12 inhibition in ST-segment elevation myocardial infarction: Bridging the gap.

Rapid and consistent platelet inhibition represents the cornerstone of pharmacologic treatment in the early hours of ST-segment elevation myocardial infarction (STEMI). Oral P2Y12 inhibitors are recommended to be administered as early as possible in patients with STEMI undergoing primary percutaneous coronary intervention. However, a delay in the onset of antiplatelet agent effects has been recently described in the first several hours after oral administration of clopidogrel, prasugrel, and ticagrelor. As a result, primary percutaneous coronary intervention is performed in most cases with P2Y12 inhibition that may be inadequate. Several strategies may be applied in order to "bridge the gap" in platelet inhibition after oral P2Y12 inhibitors in STEMI, such as upstream administration of P2Y12 inhibitors, loading dose modification, use of an intravenous P2Y12 inhibitor, or glycoprotein IIb/IIIa inhibitors' administration. These strategies may further improve clinical outcomes in this high-risk "golden window."

Reversing the effects of antiplatelet agents in the setting of intracranial hemorrhage: a look at the literature.

Patients are increasingly being prescribed antiplatelet agents (APAs) for a growing number of medical and surgical conditions. These agents are associated with an increased risk of hemorrhage, including intracranial hemorrhage (ICH). In the setting of warfarin use and ICH, strategies to reverse the drug effects have improved outcomes. No such strategy exists for APAs, and these patients continue to have poor posthemorrhage outcomes. One strategy is the use of platelet transfusions to provide functional, circulating platelets. Studies have shown mixed results regarding the benefit of this practice. Other strategies include the use of desmopressin and recombinant factor VIIa. More studies are necessary to delineate the effectiveness of the various strategies.

Early high-dose rosuvastatin and cardioprotection in the protective effect of rosuvastatin and antiplatelet therapy on contrast-induced acute kidney injury and myocardial damage in patients with acute coronary syndrome (PRATO-ACS) study.

BACKGROUND: There is a strong correlation between adverse clinical events and peak values of myocardial necrosis markers in non-ST-elevation acute coronary syndrome patients. In this clinical setting, high-dose statin treatment exerts acute beneficial effects against renal and myocardial damage. The aim of this report was to evaluate if, on admission, high-dose rosuvastatin can exert cardioprotective effects when administered in addition to high-dose clopidogrel. METHODS: In the PRATO-ACS trial, 504 consecutive statin-naïve non-ST-elevation acute coronary syndrome patients scheduled for early invasive strategy and pretreated with high-dose clopidogrel were randomly assigned to rosuvastatin (40 mg on admission followed by 20 mg/d; statin group, n = 252) or no statin treatment (control group, n = 252). Serial myocardial biomarker samples were collected before and after angiography and/or percutaneous coronary intervention. The primary end point was the peak level of cardiac troponin I (cTnI) during the index event. RESULTS: Statin-treated patients presented median cTnI peak values similar to controls (3.9 [0.6-12.8] vs 3.5 [1.2-11.9] ng/mL, respectively; P = .60]; no differences were found between the 2 groups in cTnI and creatine kinase-MB values at any time point, in either preangiography and postangiography peak values or their cumulative release. In patients submitted to percutaneous coronary intervention, periprocedural myocardial infarction occurred in 8 (4.7%) of 171 statin-treated and 7 (4.3%) of 162 control patients (P = .87). CONCLUSION: In the PRATO-ACS trial, early high-dose rosuvastatin did not show cardioprotective effects when administered in addition to high-dose clopidogrel.

Optimising pharmacotherapy for secondary prevention of non-invasively managed acute coronary syndrome.

About half of all patients who experience an acute coronary syndrome (ACS) in Australia have their conditions managed non-invasively - that is, they do not undergo coronary angiography and revascularisation in hospital. ACS patients whose conditions are managed non-invasively may not receive the same level of evidence-based care as those who receive coronary revascularisation. This article reviews the optimal pharmacological management of ACS managed non-invasively. There is strong evidence to support the prescription of dual antiplatelet therapy (DAPT; aspirin with a P2Y12 inhibitor). DAPT should continue for 12 months after an ACS, then aspirin should be continued indefinitely. Anticoagulation with warfarin or a novel oral anticoagulant may be needed if atrial fibrillation occurs; the combination with DAPT increases the risk of bleeding. Unless contraindicated, high-intensity statin therapy should be prescribed for all post-ACS patients irrespective of their cholesterol level. Non-statin lipid therapy has not been shown to improve outcomes. Use of ß-adrenergic blockers is recommended in most guidelines, but the clinical trials to support this recommendation were performed more than 30 years ago, and routine long-term use may not be relevant to modern treatment, except when there is cardiac failure or left ventricular dysfunction. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are also widely recommended, but the evidence for benefit is stronger when there is left ventricular dysfunction. Calcium-channel blockers, nitrates, antiarrhythmic drugs, digoxin and diuretics do not improve outcomes in post-ACS patients.

Switching from clopidogrel to prasugrel in patients having coronary stent implantation.

There are very few clinical data concerning the safety of switching from clopidogrel to prasugrel in patients undergoing coronary stenting. However, in the daily activity, clinicians face the decision of switching patients at high-risk of thrombotic events from clopidogrel to prasugrel. Thus, we sought to evaluate clinical events in patients undergoing coronary stent implantation and prasugrel therapy with (SWITCH group) or without (NAÏVE group) prior clopidogrel therapy. A total of 454 patients with stable or unstable coronary artery disease, aged 70 ± 10 years, underwent non-emergent stent implantation and received prasugrel therapy. Of these, 315 (69 %) patients received clopidogrel before switching to prasugrel therapy. In 239 patients with high residual platelet reactivity (HRPR) on clopidogrel, prasugrel decreased platelet aggregation from 72 ± 11 to 43 ± 16 % (p < 0.001). There was no difference in in-hospital major or minor TIMI bleeding (2.8 vs. 4.3 %; p = 0.411) between the SWITCH and NAÏVE groups as well as in mortality, acute stent thrombosis, reinfarction and stroke rates. At multivariable analysis, independent predictors of bleeding were female gender (OR 5.56 [1.41-19.88] p = 0.014) and chronic renal failure (OR 6.27 [1.59-21.65] p = 0.009), but switching therapy did not. This result was confirmed after switching propensity score adjustment (c-statistic 0.81; Hosmer-Lemeshow test p = 860). Switching from clopidogrel to prasugrel in patients undergoing non-emergent coronary stent implantation seems to be tolerated with no overt signs of increased bleeding.

Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study.

In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.

Prasugrel or double-dose clopidogrel to overcome clopidogrel low-response--the TAILOR (Thrombocytes And IndividuaLization of ORal antiplatelet therapy in percutaneous coronary intervention) randomized trial.

High on-treatment platelet reactivity (HTPR) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). The antiplatelet effect and safety of prasugrel was compared to that of double-dose clopidogrel in patients with stable coronary artery disease or acute coronary syndrome (ACS) exhibiting HTPR on clopidogrel and treated with PCI, using multiple electrode aggregometry (MEA) to assess platelet reactivity. Of 923 patients screened, 237 (25.7%) exhibited HTPR. Of these, 106 were eligible for participation in a randomized trial comparing two intensified antiplatelet regimen: 52 were assigned to double maintenance-dose clopidogrel and 54 to standard-dose prasugrel. At 1 month, tailoring antiplatelet therapy improved platelet inhibition to a level considered as therapeutic in 73.1% of patients. Prasugrel entailed greater platelet inhibition (p = 0.02) and a lower rate of persisting HTPR at follow-up compared to double-dose clopidogrel (HTPR persisted in 20.4% and 42% respectively, p = 0.02). Within the 30-day follow-up, no major bleeds were observed and the incidence of major adverse cardiovascular events (MACE) was similar in the two treatment arms. Prasugrel demonstrated superiority to double-dose clopidogrel in overcoming HTPR and reducing platelet activity. Intensifying antiplatelet therapy in both ACS and stable angina pectoris (SAP) patients exhibiting HTPR prior to PCI was well tolerated.

Should duration of dual antiplatelet therapy depend on the type and/or potency of implanted stent? A pre-specified analysis from the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY).

AIMS: The purpose of this pre-specified analysis of the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY) was to assess device-specific outcomes relative to different duration of dual antiplatelet therapy (DAPT) after Everolimus- (EES), Paclitaxel (PES), Zotarolimus- (ZES-S) eluting, or bare metal stents (BMS). METHODS AND RESULTS: We randomized 2013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group underwent up to 6 or 24 months clopidogrel therapy. The primary endpoint, which was a composite of death, myocardial infarction, or cerebrovascular accident, did not differ in patients receiving BMS [HR: 0.89 (95% CI: 0.54-1.45)], PES [HR: 0.74 (95% CI: 0.43-1.25)], or EES [HR: 0.63 (95% CI: 0.33-1.21)] implantation across DAPT groups, whereas it was significantly higher in ZES-S patients undergoing long when compared with short-term DAPT therapy (HR: 2.85, P = 0.0018), with positive interaction testing (P-value = 0.004). At the 6-month landmark analysis, heterogeneity across stent types persisted for the primary study endpoint and other secondary clinical outcomes, whereas patients receiving PES showed a significantly higher rate of definite, probable and definite, probable, possible stent thrombosis in the short DAPT regimen. No association in absolute or relative terms was noted between stent potency in inhibiting intimal hyperplasia and greater vulnerability to shorter DAPT therapy. CONCLUSION: Our study suggests that optimal duration of DAPT may be stent-specific and it does not support a clear association between stent potency and vulnerability to shorter DAPT therapy. Trial Registration clinicaltrials.gov Identifier: NCT00611286. http://clinicaltrials.gov/ct2/show/NCT00611286?term=prodigy&rank=2.

Loading dose of clopidogrel in combination with other antithrombotic therapy for capsular warning syndrome.

A 66-year-old man had repeated stereotypical transient ischemic attacks (TIAs) of dysarthria and left hemiparesis. His symptoms were considered capsular warning syndrome (CWS), for which the responsible lesion was found on magnetic resonance imaging to be in the right putamen expanding to the corona radiata. Although administration of antithrombotic therapy including aspirin was ineffective, no further TIAs occurred after a loading dose of clopidogrel was added. A loading dose of clopidogrel combined with other antithrombotic therapy might be an effective treatment for CWS.

[Perioperative management and postoperative complication rates of patients on dual antiplatelet therapies after coronary drug eluting stent implantation].

BACKGROUND: Few studies have examined the perioperative status of dual antiplatelet therapy and postoperative thrombotic or bleeding complication rates of patients undergoing non-cardiac surgery with recent history of coronary stent implantation. METHODS: Eight patients underwent surgery with antiplatelet therapy discontinued on both pre- and post-operative period (pre/postop group); 7 patients with only post-operative discontinuation (postop group); and 2 patients with therapy maintained (maintained group). All patients had history of coronary drug eluting stent implantation within 12 months of surgery. RESULTS: Antiplatelets were discontinued 7 days before surgery and restarted on postoperative day 7 for the pre/postop group, and on postoperative day 5 for postop group. Re-exploration due to bleeding complication was required in 1 patient in the postop group. Two or more units of red cell concentrate transfusion were required in 2 pre/postop, 3 postop, and 1 maintained group patients intraoperatively. No cardiac thrombotic complications including in-hospital stent thrombosis were observed, in line with previous reports of low stent thrombosis rates in Asian patients. CONCLUSIONS: In the present study, bleeding complications requiring transfusion were frequently observed in patients with dual antiplatelet therapy undergoing non-cardiac surgery, whereas perioperative therapy discontinuation did not trigger thrombotic complications including stent thrombosis.

A case of in-stent thrombosis in a patient with drug eluting stents during perioperative management with glycoprotein IIb/IIIa inhibitors.

The management of patients with drug eluting stents (DES) who require early surgical intervention prior to the completion of antiplatelet therapy is challenging. Available literature suggests that bridging these high risk patients with glycoprotein IIb/IIIa (g2b3a) inhibitors could be efficacious in preventing stent thrombosis (Ben Morrison et al., Catheter Cardiovasc Interv 2012;79;575-582). However, this still remains to be proven in larger prospective studies. We report a case of stent thrombosis in a patient with DES planned for neurosurgery while on bridging g2b3a inhibitors therapy in the perioperative period.

A prospective randomized controlled clinical trial on clopidogrel combined with warfarin versus clopidogrel alone in the prevention of restenosis after endovascular treatment of the femoropopliteal artery.

BACKGROUND: We sought to compare the effects of clopidogrel combined with warfarin with clopidogrel alone in the prevention of restenosis after endovascular treatment (EVT) of the femoropopliteal artery. METHODS: Between June 2008 and May 2009, 88 consecutive patients referred for EVT were randomly divided into a clopidogrel group (42 cases) and a clopidogrel combined with warfarin group (46 cases) before the procedure. Examinations including staging of peripheral arterial disease by Rutherford, ankle-brachial index, and color duplex ultrasonography were performed at baseline, 1 week, 3 months, 6 months, and 12 months after procedure. At the same time, bleeding complications were observed. RESULTS: Fifty patients (63 limbs) were included after 12 months of follow-up, in which 25 patients (30 limbs) were from the clopidogrel group and 25 patients (33 limbs) were from the combination group. At 3 months, the rates of restenosis on duplex ultrasonography were 17% in the clopidogrel group and 18% in the combination group (P = 1.0). At 6 months, the accumulated restenosis rates were 37% and 36% (P = 0.98), respectively. At 12 months, the accumulated restenosis rates were 53% and 42% (P = 0.523), respectively. The rate of clinical bleeding events was 21% (6/29) in the combination group compared with 7% (2/27) in the clopidogrel group, and there was no statistical difference (P = 0.3). CONCLUSIONS: The combination of clopidogrel with warfarin was not more effective than clopidogrel alone in restenosis prevention for patients who underwent EVT. Instead, the combination of antiplatelet and anticoagulation therapy was inclined to increase the clinical bleeding events.