Adenosine Diphosphate Receptor Blocker Research Articles

Institutional Variability in Red Blood Cell Transfusion With Coronary Bypass in a Statewide Database

BackgroundThe decision to perform transfusion is common but varies among centers and surgeons. This study looked at variables associated with red blood cell (RBC) transfusion in a statewide database. The study aimed to understand discrepancies in transfusion rates among hospitals and to establish whether the hospital itself was a significant variable in transfusion, independent of variables known to affect transfusion in patients undergoing cardiac surgical procedures. MethodsThe Maryland Cardiac Surgery Quality Initiative is a consortium of centers in the state. Patients undergoing isolated coronary artery bypass grafting from January 2018 to June 2020 from 10 centers in Maryland were included. Multivariable logistic regression was used to determine probability of RBC transfusion with covariates, including age, preoperative hemoglobin value, The Society of Thoracic Surgeons predicted risk of mortality, emergency status, preoperative adenosine diphosphate receptor blocker use, sex, body mass index, and off-pump status. ResultsA total of 5343 patients were included and had an overall RBC transfusion rate of 30.3% (range, 11.3%-55.8%). There was significant variability in the incidence of RBC transfusion among hospitals (χ2 = 604.7; P < .001). After covariate adjustment, a significant effect of hospital on transfusion remained (Wald = 547.3; P < .001). Hospital variation in RBC transfusion was not correlated with hospital variation in median age (P = .467), hemoglobin (P 0 855), The Society of Thoracic Surgeons predicted risk of mortality (P = .855), or sex (P = .726). ConclusionsIn a statewide analysis, wide variability in transfusion rates was observed, with hospital-specific management strongly associated with RBC transfusion. This study suggests that RBC transfusion may be affected by the culture and practices of an institution independent of clinical and demographic variables.

High On-Treatment Platelet Reactivity in Patients Undergoing Complex Percutaneous Coronary Interventions.

Patient response to P2Y12 inhibitor therapy is heterogeneous, and those with high on-treatment platelet reactivity (HTPR) are at an increased risk of thrombotic complications. The aim of our study was to determine whether selecting a high-risk patient group of individuals after complex percutaneous coronary intervention (PCI) would show the clinical benefit of HTPR testing for preventing thrombotic complications. Blood samples of patients after complex PCI were acquired 1 day and 1 month after the intervention. The samples were tested using vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) and platelet function assay (PFA). The occurrence of clinically significant stent thrombosis with repeated revascularization of the target vessel was observed over a 1-year period. One day after PCI, 37% of patients had HTPR as established by VASP-P. One month after PCI, the percentage of patients with HTPR decreased to 30.9%. According to PFA, 1 day after PCI, 33.3% of patients had HTPR. This percentage declined to 19.8% after 1 month. All measurements identified a significantly higher proportion of HTPR in patients on clopidogrel compared to ticagrelor and prasugrel. Two cases of early stent thrombosis and 1 case of late stent thrombosis were identified. Further study of adenosine diphosphate receptor blocker on-treatment response in patients undergoing complex PCI is necessary.

Resistance on the Latest Oral and Intravenous P2Y12 ADP Receptor Blockers in Patients with Acute Coronary Syndromes: Fact or Myth?

Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called "high on-treatment platelet reactivity" or "resistance") could be connected with increased risk of adverse ischemic events, such as myocardial re-infarction, target lesion failure and stent thrombosis. In addition, several risk factors have been proposed as factors associated with the phenomenon of inadequate response on novel ADPRB. These include obesity, multivessel coronary artery disease, high pre-treatment platelet reactivity and impaired metabolic status for prasugrel, as well as elderly, concomitant therapy with beta-blockers, morphine and platelet count for ticagrelor. There is no literature report describing nonoptimal therapeutic response on cangrelor, and cangrelor therapy seems to be a possible approach for overcoming HTPR on prasugrel and ticagrelor. However, the optimal therapeutic management of "resistance" on novel ADPRB is not clear and this issue requires further research. This narrative review article discusses the phenomenon of high on-treatment platelet reactivity on novel ADPRB, its importance in clinical practice and approaches for its therapeutic overcoming.

Prehospital Adenosine Diphosphate Receptor Blocker Use, Culprit Artery Flow, and Mortality in STEMI: The MADDEC Study.

Background and ObjectiveThe newer adenosine diphosphate (ADP) receptor blockers ticagrelor and prasugrel are superior to clopidogrel in the long-term management of acute coronary syndrome (ACS). We evaluated the acute performance (prehospital loading) of these ADP receptor blockers in a primary percutaneous coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI).MethodsIn a retrospective, single-center registry study, data on all STEMI patients admitted for their first primary PCI between January 2007 and April 2020 were analyzed (n = 3218). The three ADP receptor blockers were mainly used during consecutive periods (clopidogrel 2007–2010, prasugrel 2011–2014, and ticagrelor 2014–2020), and were compared with risk factor-adjusted multivariate logistic regression for acute 3- and 7-day mortality and culprit artery flow before and after PCI.ResultsOf the 3218 total patients, 47.6% (n = 1532) were treated with ticagrelor, 22.1% (n = 711) were treated with prasugrel, and 30.3% (n = 975) were treated with clopidogrel. The use of ticagrelor or prasugrel as opposed to clopidogrel was associated with better culprit artery flow before PCI (odds ratio [OR] 1.21 for moderate or good flow, 95% confidence interval [CI] 1.03–1.42, p = 0.022), as well as lower acute mortality (OR 0.66 for 3-day mortality, 95% CI 0.46–0.95, p = 0.025; and OR 0.71 for 7-day mortality, 95% CI 0.52–0.98, p = 0.039). The results in regard to acute mortality were highlighted among patients with short treatment delays (disappearing with longer treatment delays; p < 0.05 for interaction).ConclusionsThe newer ADP receptor blockers are associated with lower mortality and better culprit artery flow at presentation when compared with clopidogrel. There are no significant differences between the two newer drugs. As the drugs were mainly used during three consecutive periods, unmeasured confounding related to the development of cardiac care and changes in the population may contribute to the results.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-021-01045-2.

Overlooked hepatotoxicity with Clopidogrel

Clopidogrel is an adenosine diphosphate receptor blocker. It is widely used as a part of dual antiplatelet therapy (DAPT) in patients with ischemic heart disease (IHD), regardless of the acute coronary syndrome (ACS). Although a rarely reported entity, clopidogrel-induced liver injury is commonly seen in clinical practice. It is widely overlooked by clinicians and is thus a potential hazard to patients with IHD.

Intravenous glycoprotein IIbIIIa inhibitor bridging for urgent coronary artery bypass graft after acute coronary syndrome

Abstract Background Previous studies have shown the safety of intravenous glycoprotein (GP) IIbIIIa inhibitors used as a bridging after ADP receptor blocker withdrawal in patients with stable coronary artery disease and previous percutaneous coronary interventions (PCI) undergoing cardiac or non-cardiac surgeries. However, there are few data analyzing GP IIbIIIa inhibitor bridging among patients with acute coronary syndromes (ACS) scheduled for coronary artery bypass graft (CABG) during the same hospitalization. Purpose To evaluate the safety of tirofiban bridging after clopidogrel withdraw in post-ACS patients schedule for CABG during the same hospitalization. Methods Fifty-six patients who underwent CABG after tirofiban bridging post-ACS (bridge group - BG) were compared to 56 sex and age-matched controls also submitted to same-hospitalization CABG post-ACS without bridging (control group - CG). All patients received aspirin plus clopidogrel for ACS; clopidogrel was withdrawn 5 to 7 days before CABG and aspirin was maintained during the whole perioperative period. The primary endpoint was chest tube output in the first 24h after CABG (CTO24h). We hypothesized that BG would be non-inferior to CG, with a non-inferiority margin of 25% in excess of CTO24h in the BG compared to the CG, based on prior literature data. Other exploratory analyses were: blood transfusions, number of red blood cells/patient and re-thoracotomy 24h after surgery. A multivariable linear regression model was developed considering CTO24h as dependent variable and adjusted for other eight co-variates, described in the figure. Results From the 112 patients included (75% men; mean age 60.2±9.3 years), in comparison with CG, BG had higher proportion of STEMI (80.0% vs. 28.6%, p&amp;lt;0.01), fibrinolytic utilization (25% vs. 7.1%, p&amp;lt;0.05), PCI in the acute phase (92.9% vs. 0%, p&amp;lt;0.01) and LMCA stenosis (30.4% vs. 7.1% p&amp;lt;0.01). Tirofiban was utilized by clinician discretion due to PCI in the same hospitalization previously to CABG (n=52), previous PCI up to 3 months before index event (n=3) or severe LMCA stenosis (n=1). BG patients received tirofiban for a mean of 4.3±2.1 days and it was withdrawn at a mean of 6.6±4.3 hours before CABG. After adjustments, BG was non-inferior to CG regarding CTO24h (figure) There were no significant differences between BG and CG regarding need for blood transfusion (26.8% vs. 26.8%, p&amp;gt;0.99), mean number of red blood cells/patient (0.3±0.8 vs 0.5±1.2, p=0.35) or re-thoracotomy due to bleeding (5.4% vs 0%, p=0.24). Conclusion Among ACS patients submitted to urgent CABG after clopidogrel withdrawal, tirofiban bridging, compared to no bridging, was not associated with higher risk of bleeding in the first 24 hours after surgery. Our study suggests that tirofiban may be a safe therapy to patients with high risk of thrombotic complication (such as stent thrombosis or re-infarction) after clopidogrel withdraw. Figure 1 Funding Acknowledgement Type of funding source: None

Disorders on cardiovascular parameters in rats and in human blood cells caused by Lachesis acrochorda snake venom

In Colombia, Lachesis acrochorda causes 2–3% of all snake envenomations. The accidents promote a high mortality rate (90%) due to blood and cardiovascular complications. Here, the effects of the snake venom of L. acrochorda (SVLa) were analyzed on human blood cells and on cardiovascular parameters of rats. SVLa induced blood coagulation, as measured by the prothrombin time test, but did not reduce the cell viability of neutrophils and platelets evaluated by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by the lactate dehydrogenase (LDH) enzyme assay. In fact, SVLa increased the absorbance in tests made with platelets subjected to the MTT assay. SVLa induced platelet aggregation whose magnitude was comparable to that of the positive control adenosine diphosphate (ADP), and occurred earlier with increasing SVLa concentration. Acetylsalicylic acid (ASA, a cyclooxygenase inhibitor) or clopidogrel (an ADP receptor blocker) inhibited the aggregating effect of SVLa. Inhibition of SVLa-elicited platelet aggregation also resulted from the treatment with disodium ethylenediaminetetraacetate (Na2-EDTA; metalloproteinase inhibitor) and with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF, serine protease inhibitor). In isolated right atrium of rats, SVLa increased slightly, but significantly, the magnitude of the spontaneous contractions and, in isolated rat aorta, SVLa relaxed KCl- or phenylephrine-induced contractions. In vivo, SVLa induced hypotension and bradycardia in rats, with detection of hemorrhage in pulmonary and renal tissues. Altogether, under experimental conditions, SVLa induced blood coagulation, platelet aggregation, hypotension and bradycardia. Part of the effects presented here may be explained by the presence of snake venom metalloproteinases (SVMPs) and snake venom serine proteases (SVSPs), constituents of SVLa.

Morphine and Cardiovascular Outcomes Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Coronary Angiography

BackgroundMechanistic studies have shown that morphine blunts the antiplatelet effects of oral adenosine diphosphate receptor blockers. However, the clinical relevance of this interaction is controversial. ObjectivesThis study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls. MethodsEndpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 h (4-way endpoint) and the composite of death or MI at 30 days. ResultsIn patients treated with clopidogrel, morphine use was associated with higher rates of the 4-way endpoint at 96 h (adjusted odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.04 to 1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR: 1.29; 95% CI: 0.98 to 1.70; p = 0.072), driven by events in the first 48 h (adjusted hazard ratio: 1.54; 95% CI: 1.07 to 2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the 4-way endpoint at 96 h (adjusted OR: 1.05; 95% CI: 0.74 to 1.49; p = 0.79; pinteraction = 0.36 ) or death or MI at 30 days (adjusted OR: 1.07; 95% CI: 0.77 to 1.48; p = 0.70; pinteraction = 0.46). ConclusionsWhen used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome; NCT00089895)

Incidence, predictors, and prognosis of premature discontinuation or switch of prasugrel or ticagrelor: the ATLANTIS - SWITCH study

Aim of the present study was to investigate the frequency and predictors of premature discontinuation or switch of ADP receptor blockers and its association with serious adverse events. For this purpose 571 consecutive ACS patients receiving ticagrelor (n = 258, 45%) or prasugrel (n = 313, 55%) undergoing PCI were enrolled in this prospective, observational, multicenter ATLANTIS-SWITCH substudy. Predictors of premature discontinuation or switch of antiplatelet therapy and their association with major adverse cardiovascular events and TIMI bleeding events were evaluated. Premature stop/switch was found in 72 (12.6%) patients: 34 (5.9%) stopped and 38 (6.7%) switched the ADP blocker. Ticagrelor treated patients were significantly more likely to stop/switch therapy as compared to prasugrel (15.9% vs. 9.2%, p = 0.016). We identified 4 independent predictors for stop/switch of ADP blocker: major surgery, need for oral anticoagulation (OAC), TIMI major bleeding and drug intolerance. TIMI major bleeding was a driver of stop/switch actions and occurred in 4.3% vs 0.2% in patients with vs without stop/switch (p = 0.001). The majority of stop/switch actions (75%) were physicians driven decisions. Importantly, stop/switch of therapy was not associated with increased risk of MACE (p = 0.936). In conclusion premature switch/stop of ADP blockers appears to be safe when mainly driven by physician’s decision and clinical indication.

On-treatment platelet reactivity in the era of new ADP receptor blockers: data from a real-world clinical practice

Abstract Objectives: Several studies have questioned the need for platelet function testing in patients treated with new ADP receptor blockers (ADPRB). The aim of this study was to evaluate the prevalence of high on-treatment platelet reactivity (HTPR) among acute ST-elevation myocardial infarction (STEMI) patients treated with newer ADPRB. Methods: A prospective study enrolling 44 acute previously ADPRB naive STEMI patients (31 men, 13 women) undergoing primary percutaneous coronary intervention (pPCI) was performed. Among the studied population 23 patients received prasugrel and 21 patients received ticagrelor. Antiplatelet response was tested with light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Samples were taken prior to coronary angiography (sample 1) and on the day after this procedure (sample 2). Results: The mean platelet aggregation after induction with ADP was 51.7 ± 24.8% in sample 1 and 25.3 ± 20.1% in sample 2. An examination of VASP-P showed a mean platelet reactivity index of 56.8 ± 25.7% in sample 1 and 23.8 ± 23.1% in sample 2, respectively. The study identified 11.4% of patients in sample 2 as ADP receptor blocker non-responders. No significant differences were found between prasugrel-treated to ticagrelor-treated patients. Conclusions: This pilot study demonstrated HTPR among acute STEMI patients treated with newer ADPRB.

The effect of cessation of 2nd generation P2Y12 inhibitor therapy on platelet reactivity in patients 1 year after acute myocardial infarction.

To assess the effect of cessation of dual antiplatelet therapy (DAPT) regimens containing 2nd generation P2Y12 inhibitors on platelet reactivity, in patients who completed 12months of DAPT following an acute myocardial infarction. Clinical data has shown an increased cardiovascular risk in the 90days following cessation of DAPT. One possible explanation is a transient platelet hyper-reactivity after cessation of treatment. Data from patients treated with 2nd generation P2Y12 inhibitors is scarce. Patients who completed 12month DAPT with prasugrel/ticagrelor underwent serial assessment of platelet reactivity (on DAPT and 1, 4 and 12weeks post cessation). The primary outcome was platelet reactivity, expressed as platelet reactivity units (PRU) at each time point. 41 participants were included in this study, (23 ticagrelor, 18 prasugrel). There was no statistically significant differences in baseline characteristics between prasugrel/ticagrelor treated patients . The pattern of platelet reactivity recovery after DAPT cessation differed between the ticagrelor and prasugrel: with ticagrelor, after the initial PRU increase from baseline, the PRU remained stable, while with prasugrel, there was a further increase in PRU between 1 and 4weeks, with a return to the 1week level by 12 weeks (p = 0.034 for the time × treatment interaction between ticagrelor and prasugrel). Our results suggest there is a transient platelet hyper-reactivity after cessation of ADP receptor blockers therapy with prasugrel, but not ticagrelor. Further research is required to elucidate the pathophysiologic mechanisms behind these findings and to evaluate potential strategies to prevent or overcome this "rebound" effect.

Powerful P2Y12 inhibition after percutaneous coronary intervention for an acute coronary syndrome: “the times they are a changing”

DAPT using aspirin and a P2Y12 platelet ADP receptor blocker has been established since more than 20 years as the pharmacological background of percutaneous coronary intervention (PCI) and post-acute coronary syndrome (ACS) ( Table 1 ). First, the combination of aspirin and ticlopidine given for 30 days has shown superiority over aspirin and anticoagulant therapy in patients undergoing coronary artery stenting (1).

Does Pantoprazole Affect the On-Treatment Platelet Reactivity in Patients With Acute STEMI Treated With ADP Receptor Blockers?-A Pilot Prospective Study.

Proton pump inhibition (PPI) administrated together with adenosine diphosphate (ADP) receptor blockers (ADPRB) significantly reduces the risk of gastrointestinal bleeding. Nevertheless, there is a heated discussion about an interaction between PPI and ADPRB that leads to high on-treatment platelet reactivity (HTPR). Is there a relationship between pantoprazole PPI and HTPR on ADPRB therapy in patients with acute ST-elevation myocardial infarction (STEMI). Single center pilot study in patients with acute STEMI was performed. This study enrolled totally 87 patients (34 clopidogrel-treated and 53 new ADPRB-treated patients). Pantoprazole was administrated in 33 patients. HTPR was detected with ADP-induced light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation analysis. Samples were taken before coronary angiography (sample 1) and on the next day after the procedure (sample 2). No significant differences were found in pantoprazole-treated patients and patients without PPI neither in sample 1 (59.2 ± 29.5% vs. 54.9 ± 22.7%, P = 0.49) nor in sample 2 (43.8 ± 27.2% vs. 37.0 ± 22.9%, P = 0.30). Similarly, there were no significant differences in the platelet reactivity index of vasodilator-stimulated phosphoprotein phosphorylation in both samples (sample 1: 53.3 ± 29.8% vs. 65.0 ± 20.5%, P = 0.11; sample 2: 30.8 ± 27.1% vs. 40.6 ± 27.5%, P = 0.19). A comparison of clopidogrel and new ADP receptor blockers in patients on pantoprazole PPI did not reveal significant differences in on-treatment platelet reactivity. This study did not reveal interaction between pantoprazole and ADPRB in patients with acute STEMI.

Abciximab as a bridging strategy to overcome morphine-prasugrel interaction in STEMI patients.

The present study investigated whether the glycoprotein (GP)IIb/IIIa receptor blocker abciximab might be a successful bridging strategy to achieve adequate levels of platelet inhibition rapidly in cases where prasugrel is used in morphine-pretreated ST-elevation myocardial infarction (STEMI) patients. In a prospective observational cohort study, 32 patients presenting with STEMI were given prasugrel at a loading dose of 60mg. Patients were stratified into four groups, according to morphine and/or abciximab use. Adenosine diphosphate (ADP)-induced platelet aggregation was measured at four time points: at baseline, and at 2h, 1day and 2days after prasugrel loading. Morphine use was associated with a three-fold higher level of ADP-induced platelet aggregation 2h after prasugrel loading compared with no morphine/no abciximab (P = 0.019). However, when abciximab was infused in the catheterization laboratory, the effect of morphine on ADP-induced platelet aggregation disappeared (P = 0.884). This interaction was also seen in the presence of high on-treatment platelet reactivity (HTPR) at 2 h; while HTPR was seen in 88% of morphine users/no abciximab users, it was found in only 17-20% in the three other groups (P = 0.003). The effect of morphine disappeared by day 1 - 2. The infusion of the GPIIb/IIIa receptor blocker abciximab allows immediate and efficient platelet inhibition in STEMI patients concomitantly receiving the oral ADP receptor blocker prasugrel and morphine.

Ticagrelor: a safe and effective approach for overcoming clopidogrel resistance in patients with stent thrombosis?

Stent thrombosis is a morbid complication following percutaneous coronary intervention (PCI). Dual antiplatelet therapy significantly reduces stent thrombosis risk. However, the antiplatelet response to clopidogrel - the most frequently used ADP receptor antagonist in post-PCI patients - varies among individuals. High on-treatment platelet reactivity was repeatedly associated with the risk of stent thrombosis. Ticagrelor is a novel ADP receptor blocker that has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. This agent offers a unique mechanism of action, no relevant pharmacological interactions, consistent platelet inhibition, and a good safety profile. This article reviews the prospective use of ticagrelor in the treatment of stent thrombosis in acute coronary syndrome patients undergoing PCI of culprit coronary lesion.

The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective Study.

Background. The aim of this study was to validate the impact of type 2 diabetes (T2D) on the platelet reactivity in patients with acute ST elevation myocardial infarction (STEMI) treated with adenosine diphosphate (ADP) receptor blockers. Methods. A pilot prospective study was performed. Totally 67 patients were enrolled. 21 patients had T2D. Among all study population, 33 patients received clopidogrel and 34 patients received prasugrel. The efficacy of ADP receptor blocker therapy had been tested in two time intervals using light transmission aggregometry with specific inducer and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Results. There were no significant differences in platelet aggregability among T2D and nondiabetic (ND) group. The platelet reactivity index of VASP-P did not differ significantly between T2D and ND group (59.4 ± 30.9% versus 60.0 ± 25.2% and 33.9 ± 25.3% versus 38.6 ± 29.3% in second testing). The number of ADP receptor blocker nonresponders did not differ significantly between T2D and ND patients. The time interval from ADP receptor blocker loading dosing to the blood sampling was similar in T2D and ND patients in both examinations. Conclusion. This prospective study did not confirm the higher platelet reactivity and higher prevalence of ADP receptor blocker nonresponders in T2D acute STEMI patients.

A Review: Determination of Clopidogrel Bisulphate in Biological Fluid and Pharmaceutical Dosage Forms

Clopidogrel Bisulphate is a mainly use in Anti platelet agent as a ADP receptor blocker and administration of oral tablet dosage form. Chemically, it is Methyl 2-(2-Chlorophenyl) -2-(6, 7-dihydro thieno [3,2-C] Pyridine5(4H)-yl) Acetate sulphate. It is used in the treatment of various cardiovascular diseases like Ischemic stroke as well as in Glomerular inflammation, Myocardial infarction, Atherosclerosis disease, Unstable Angina. An extensive survey of the literature published in various analytical and pharmaceutical chemistry related journals has been conducted and the instrumental analytical methods which were developed and used for determination as single or combination with other drugs in bulk drugs, formulations and biological fluids have been reviewed. These reviews of analytical methods including Spectrophotometric methods like Spectrophotometry, Chromatographic method including HPLC, HPTLC were reported.

Prevention of cardiovascular events with antiplatelet treatment: does time of intake matter for aspirin and ADP receptor blockers?

Long-term evidence supports a clustering of cardiovascular events in the early morning. Several studies have shown that platelet hyper-reactivity to various stimuli is also present at this period of the day. However, the idea of treatment strategies reflecting the circadian variation in platelet reactivity has been largely neglected so far, and this is true despite the huge number of patients being treated with these drugs. Some pharmacodynamic data suggest that early-morning platelet hyper-reactivity may be overcome by shifting aspirin intake to the bedtime. However, there is lack of evidence whether shifting the time of intake or splitting the daily dose of P2Y12-inhibitors with a regular QD dosing (clopidogrel or prasugrel) to the evening would be effective to overcome platelet hyper-reactivity or to suppress the excess of cardiovascular events observed during morning hours. Further research is warranted to clarify whether such a simple and costless effort like dose shifting or splitting may be beneficial to prevent cardiovascular events.

Type 2 Diabetes and ADP Receptor Blocker Therapy.

Type 2 diabetes (T2D) is associated with several abnormalities in haemostasis predisposing to thrombosis. Moreover, T2D was recently connected with a failure in antiplatelet response to clopidogrel, the most commonly used ADP receptor blocker in clinical practice. Clopidogrel high on-treatment platelet reactivity (HTPR) was repeatedly associated with the risk of ischemic adverse events. Patients with T2D show significantly higher residual platelet reactivity on ADP receptor blocker therapy and are more frequently represented in the group of patients with HTPR. This paper reviews the current knowledge about possible interactions between T2D and ADP receptor blocker therapy.

Development of a concept for a personalized approach in the perioperative antiplatelet therapy administration/discontinuation management based on multiple electrode aggregometry in patients undergoing coronary artery surgery.

In patients undergoing coronary artery surgery, improvements in clinical outcomes currently rely on continued refinements of the surgical technique and modulation of adjuvant pharmacotherapy. Despite medical and technological advances, negligible rate of bleeding and ischemic events still persist necessitating further improvements in patient management. Platelet function testing (PFT) might play an important role in meticulous balancing between the risk of bleeding and thrombotic events. A suitable balance can be achieved by implementing a personalized, PFT based approach in antiplatelet therapy (APT) administration/discontinuation management. Despite emerging evidence on the widespread variability in platelet inhibitory response to APT, numerous PFT devices and heterogeneity in reporting study results hamper pooling of the evidence which in turn results with a lack of consensus in "on treatment" platelet reactivity associated with ischemic and bleeding events in perioperative phase. The literature on multiple electrode aggregometry (Multiplate(®); Roche Diagnostics, Mannheim, Germany) in coronary artery disease patients was reviewed systematically. Based on the evidence evaluating the relationship between "drug specific" PFT and bleeding or adverse ischemic events, we sought to define therapeutic window for the most commonly administered antiplatelet drugs such as aspirin (ASPI test) and adenosine-diphosphate receptor blockers (ADP test). Preoperatively, APT administration was primarily focused to avoid bleeding complications. ASPI test value of 20 AUC and ADP test value of <73 AUC were set as cut-off values that delineate bleeding tendency. Postoperatively, "therapeutic window" was set to avoid both bleeding and adverse ischemic events. Therapeutic ranges were as follows: 20 AUC < ASPItest ≤ 30 AUC and 19AUC < ADP ≤ 46AUC, respectively. This is the first attempt to define PFT based "therapeutic window" according to, perioperative APT administration/discontinuation management would be targeted. It seems that the "one-size-fits-all" concept of perioperative APT administration management is outdated and further development of PFT based, personalized APT administration/discontinuation management is desirable. This concept therefore presents a possible step forward in patient care and provides a platform for further interventional trials whereby the impact of its application on clinical outcomes would be validated.