Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Shorter (≤ 6 months) Versus Longer (≥12 months) Duration Dual Anti-platelet Therapy After Drug Eluting Stents: A Meta-Analysis Of Randomized Clinical Trials. [JOURNAL ARTICLE]
- Catheter Cardiovasc Interv 2014 Apr 18.
Objective Optimal duration of dual anti-platelet therapy, defined as use of both aspirin and a P2Y12 receptor inhibitor, after implantation of drug eluting stents is still subject of ongoing debate. We systematically review efficacy and safety of ≤6 months versus ≥ 12 months dual anti-platelet therapy after implantation of drug eluting stents. Methods PubMed, Scopus, Cochrane and clinicaltrials.gov databases were searched for studies published until 30(th) November 2013. The studies were limited to randomized clinical trials. Independent observers abstracted the data on outcomes, characteristics and qualities of studies included. Random effect model was employed for meta-analysis. Heterogeneity of studies included was analyzed using I(2) statistics. Results In four randomized clinical trials published involving 8163 patients with drug eluting stents, 4081 patients were randomized to shorter and 4082 patients to longer duration dual anti-platelet therapy. The P2Y12 receptor inhibitor used in all four studies was clopidogrel. Longer duration of dual anti-platelet therapy did not reduce risk of all cause mortality (pooled OR 0.89, 95% CI 0.67-1.17, P = 0.4, I(2) = 0%), myocardial infarction (pooled OR 1.16, 95% CI 0.85-1.57, P = 0.35, I(2) = 0%) cardiac death (pooled OR 0.88, 95% CI 0.61-1.25, P = 0.47, I(2) = 0%), stent thrombosis (pooled OR 1.29, 95% CI 0.76-2.21, P = 0.35, I(2) = 0%) or cerebrovascular accidents (pooled OR 0.73, 95% CI 0.41-1.27, P = 0.26, I(2) = 0%). Longer duration of dual anti-platelet therapy was associated with increased risk of TIMI major bleeding (pooled OR 0.51, 95% CI 0.29-0.89, P = 0.02, I(2) = 0%). Conclusion There was no difference in efficacy outcomes between ≤ 6 months of dual anti-platelet therapy and ≥ 12 months of dual anti-platelet therapy in patients with coronary artery disease and drug eluting stent implantation. Moreover, longer duration of dual anti-platelet therapy is associated with increased risk of bleeding complications. © 2014 Wiley Periodicals, Inc.
- Genetics of response to antiplatelet therapy. [Journal Article]
- Prog Mol Biol Transl Sci 2014.:123-53.
Dual antiplatelet therapy has a major role in the management of acute coronary syndromes (ACS) and following percutaneous coronary intervention (PCI). However, significant variation in pharmacodynamic response to antiplatelet therapy has been demonstrated, especially to clopidogrel. Single nucleotide polymorphisms, particularly those affecting the metabolism of antiplatelet therapy, account for some, but not all, of this variability in response. Loss-of-function polymorphisms of CYP2C19, the gene encoding for the key enzyme in the metabolism of clopidogrel, are associated with reduced formation of the active metabolite of clopidogrel, a lower pharmacodynamic effect of the drug and a corresponding increase in adverse cardiovascular events. Conversely, gain-of-function polymorphisms of CYP2C19 are associated with an increased pharmacodynamic response to the drug and therefore an increase in bleeding. The clinical relevance of other polymorphisms that affect antiplatelet therapy has not been clearly established.
- [Mean platelet volume: interactions with platelet aggregation activity and glycoprotein IIb-IIIa and Ib expression levels]. [English Abstract, Journal Article]
- Biomed Khim 2014 Jan-Feb; 60(1):94-108.
Increased mean platelet volume (MPV) is an independent risk factor of thrombotic events in patients with cardiovascular diseases. Interactions of MPV with platelet aggregation activity and contents of glycoprotein (GP) IIb-IIIa (alphaIIb/beta3 integrin, fibrinogen receptor) and GP Ib (von Willebrand factor receptor) were investigated in this study. Investigation was performed in a group of healthy volunteers (n = 38) and in a group of patients with acute coronary syndrome (ACS). In patients blood was collected at days 1, 3-5 and 8-12 after ACS development. As an antiaggregant therapy all patients received acetylsalicylic acid (ASA, inhibitor of thromboxane A2 synthesis) and most of them--clopidogrel (ADP receptor antagonist) with the exception of part of the patients (n = 44) at day 1 who had not taken clopidogrel before first blood collection. In volunteers platelet aggregation was stimulated by 1.25, 2.5, 5 and 20 M ADP, and in patients--by 5 and 20 M ADP. GP IIb-IIIa and GP Ib content on platelet surface was measured using 125I-labelled monoclonal antibodies. GP IIb-IIIa and GP Ib genetic polymorphisms were determined in ACS patients. In healthy donors significant correlations between MPV and aggregation levels were revealed at 1.25 and 2.5 M ADP (coefficients of correlation (r)--0.396 and 0.373, p < 0.05) and at 5 and 20 those interactions did not reach significant level (r--0.279 and 0.205, p > 0.05). Correlations between MPV and aggregation levels were observed at day 1 of ACS in a subgroup of patients who received ASA but had not started clopidogrel treatment (r--0.526, p < 0.01 and 0.368, p < 0.05 for 5 and 20 M ADP respectively). Interactions between these parameters were not registered upon combined treatment with ASA and clopidogrel. Strong direct correlations between MPV and GP IIb-IIIa and GP Ib contents were detected in healthy donors and ACS patients (at all time points) -r from 0.439 to 0.647 (p < or = 0.001 for all correlations). Genetic polymorphisms of GP IIb-IIIa (GP IIIa Leu33Pro) and GP Ib ((-5)T/C (Kozak) and Thr145Met) identified in ACS patients did not affect expression levels of corresponding glycoproteins. The data obtained indicated that increased MPV values correlate with increased platelet aggregation activity and enhanced GP IIb-IIIa and GP Ib expression.
- Traumatic brain injury causes platelet adenosine diphosphate and arachidonic acid receptor inhibition independent of hemorrhagic shock in humans and rats. [Journal Article]
- J Trauma Acute Care Surg 2014 May; 76(5):1169-76.
Coagulopathy in traumatic brain injury (CTBI) is a well-established phenomenon, but its mechanism is poorly understood. Various studies implicate protein C activation related to the global insult of hemorrhagic shock or brain tissue factor release with resultant platelet dysfunction and depletion of coagulation factors. We hypothesized that the platelet dysfunction of CTBI is a distinct phenomenon from the coagulopathy following hemorrhagic shock.We used thrombelastography with platelet mapping as a measure of platelet function, assessing the degree of inhibition of the adenosine diphosphate (ADP) and arachidonic acid (AA) receptor pathways. First, we studied the early effect of TBI on platelet inhibition by performing thrombelastography with platelet mapping on rats. We then conducted an analysis of admission blood samples from trauma patients with isolated head injury (n = 70). Patients in shock or on clopidogrel or aspirin were excluded.In rats, ADP receptor inhibition at 15 minutes after injury was 77.6% ± 6.7% versus 39.0% ± 5.3% for controls (p < 0.0001). Humans with severe TBI (Glasgow Coma Scale [GCS] score ≤ 8) showed an increase in ADP receptor inhibition at 93.1% (interquartile range [IQR], 44.8-98.3%; n = 29) compared with 56.5% (IQR, 35-79.1%; n = 41) in milder TBI and 15.5% (IQR, 13.2-29.1%) in controls (p = 0.0014 and p < 0.0001, respectively). No patient had significant hypotension or acidosis. Parallel trends were noted in AA receptor inhibition.Platelet ADP and AA receptor inhibition is a prominent early feature of CTBI in humans and rats and is linked to the severity of brain injury in patients with isolated head trauma. This phenomenon is observed in the absence of hemorrhagic shock or multisystem injury. Thus, TBI alone is shown to be sufficient to induce a profound platelet dysfunction.
- The use of platelet function testing in PCI and CABG patients. [JOURNAL ARTICLE]
- Blood Rev 2014 Apr 1.
Antiplatelet drugs are widely used in the treatment of patients with coronary artery disease. Dual anti-platelet therapy with acetylsalicylic acid (ASA) and a P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) is the recommended strategy for patients undergoing a percutaneous coronary intervention (PCI), while patients that undergo coronary artery bypass grafting (CABG) are treated with ASA monotherapy. However, the response to these drugs as assessed with platelet function tests varies between patients. Despite these drugs, many patients still exhibit high on-treatment platelet reactivity (HPR), while platelet reactivity seems to be excessively inhibited in other patients. This review will discuss the use of platelet function testing in the prediction of atherothrombotic and bleeding events in patients undergoing PCI or CABG. Furthermore, options for tailoring based on platelet function testing in these patients are described.
- Association of P2Y12 Gene Promoter DNA Methylation with the Risk of Clopidogrel Resistance in Coronary Artery Disease Patients. [Journal Article]
- Biomed Res Int 2014.:450814.
Background.Clopidogrel inhibits the ADP receptor P2Y12 to keep down the platelet aggregation. The goal of our study is to investigate the contribution of P2Y12 promoter DNA methylation to the risk of clopidogrel resistance (CR). Methods. The platelet functions were measured by the VerifyNow P2Y12 assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides on P2Y12 promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association among P2Y12 DNA methylation, various biochemical characteristics, and CR. Result. Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1, P = 0.009; CpG2, P = 0.022) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients (P = 0.026) and in subgroup of Albumin < 35 (P = 0.002). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR.
Conclusions.The evidence from our study indicates that P2Y12 methylation may bring new hints to elaborate the pathogenesis of CR.
- Thrombocytosis is associated with increased short and long term mortality after exacerbation of chronic obstructive pulmonary disease: a role for antiplatelet therapy? [JOURNAL ARTICLE]
- Thorax 2014 Apr 17.
Evidence suggests that platelets play a significant role in inflammation in addition to their role in thrombosis. Systemic inflammation is linked to poor short and long term outcomes in COPD. Increased platelet activation has been reported in acute exacerbations of COPD (AECOPD). We investigated whether thrombocytosis is independently associated with poor outcomes following AECOPD.An observational cohort study of patients hospitalised with AECOPD was performed. Patients were >40 years with spirometry confirmed COPD admitted between 2009 and 2011. Platelet count was recorded on admission. The primary outcome was 1-year all-cause mortality. Secondary outcomes included inhospital mortality and cardiovascular events. Analyses were conducted using logistic regression after adjustment for confounding variables.1343 patients (49% male) were included. Median age was 72 years (IQR 63-79 years). 157 (11.7%) had thrombocytosis. Thrombocytosis was associated with both 1-year mortality and inhospital mortality; OR 1.53 (95% CI 1.03 to 2.29, p=0.030) and OR 2.37 (95% CI 1.29 to 4.34, p=0.005), respectively. Cardiovascular hospitalisation was not significantly increased (OR 1.13 (95% CI 0.73 to 1.76, p=0.600)) in patients with thrombocytosis. Aspirin or clopidogrel treatment correlated with a reduction in 1-year mortality (OR 0.63 (95% CI 0.47 to 0.85, p=0.003)) but not inhospital mortality (OR 0.69 (95% CI 0.41 to 1.11, p=0.124)).After adjustment for confounders thrombocytosis was associated with increased 1-year mortality after exacerbation of COPD. Antiplatelet therapy was associated with significantly lower 1-year mortality and may have a protective role to play in patients with AECOPD.
- Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy. [JOURNAL ARTICLE]
- J Transl Med 2014 Apr 17; 12(1):101.
We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA).A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period.As compared with the baseline, circulating endothelial progenitor cell level (as shown by flow cytometry) was significantly increased (p < 0.003), whereas the CLI-related ulcers and painfulness were significantly improved (all p < 0.01) by day 90 after treatment. On the other hand, after clopidogrel and cilostazol combination therapy, galectin-3 level, lipoprotein-associated phospholipase A2 gene expression, and RhoA/ROCK-related protein expression in peripheral blood mononuclear cells were significantly suppressed (all p < 0.01). Eventually, by day 90, 5 patients (9.1%) died of other etiologies, 3 (5.5%) withdrew from the study, 6 (10.9%) required amputation, and the remaining 41 had satisfactory clinical improvement with complete wound healing in 9 (16.4%) patients.The results of the present study highlight that clopidogrel and cilostazol combination therapy may be considered to be an alternative method for treating patients with CLI unsuitable for surgical revascularization or PTA.
- A study of potential drug-drug interactions among hospitalized cardiac patients in a teaching hospital in Western Nepal. [Journal Article]
- Indian J Pharmacol 2014 Mar; 46(2):152-6.
Drug-drug interaction (DDI) is of major concern in patients with complex therapeutic regimens. The involvement of cardiovascular medicines in drug interaction is even higher. However, reports of DDI between these groups of drugs are few. The study aims to identify the potential DDI among hospitalized cardiac patients. Furthermore, we assessed the possible risk factors associated with these interactions.The Type of study prospective observational study was conducted from May 2012 to August 2012 among hospitalized cardiac patients. Cardiac patients who were taking at least two drugs and who had a hospital stay of at least 24 h were enrolled. The medications of the patients were analyzed for possible interactions using the standard drug interaction database - Micromedex -2 (Thomson Reuters) × 2.0.From a total of 150 enrolled patients, at least one interacting drug combination was identified among 32 patients. The incidence of potential DDI was 21.3%. A total of 48 potentially hazardous drug interactions were identified. Atorvastatin/azithromycin (10.4%), enalapril/metformin (10.4%), enalapril/potassium chloride (10.4%), atorvastatin/clarithromycin (8.3%) and furosemide/gentamicin (6.3%) were the most common interacting pairs. Drugs most commonly involved were atorvastatin, enalapril, digoxin, furosemide, clopidogrel and warfarin. Majority of interactions were of moderate severity (62.5%) and pharmacokinetic (58.3%) in nature. Increased number of medicines, prolonged hospital stays and comorbid conditions were the risk factors found associated with the potential DDI.This study highlighted the need of intense monitoring of patients who have identified risk factors to help detect and prevent them from serious health hazards associated with drug interactions.
- A Comparative Study of Dual versus Monoantiplatelet Therapy in Patients with Acute Large-Artery Atherosclerosis Stroke. [JOURNAL ARTICLE]
- J Stroke Cerebrovasc Dis 2014 Apr 13.
Antiplatelet drugs are recommended for patients with acute noncardioembolic stroke. However, few randomized clinical trials have investigated the safety and efficacy of dual antiplatelet therapy for these patients. The aim of this study was to evaluate the effects of treatment with clopidogrel and aspirin (combination therapy) and aspirin alone (monotherapy) on neurologic deterioration, platelet activation, and other short-term outcomes in patients with acute large-artery atherosclerosis stroke.Altogether 574 patients with acute (≤2 days) large-artery atherosclerosis stroke were randomly assigned to receive either combined clopidogrel and aspirin or aspirin alone. Platelet aggregation and platelet-leukocyte aggregation studies were performed at days 1 and 30. Primary outcomes including recurrent ischemic stroke, neurologic deterioration, periphery vascular events, and myocardial infarction were monitored. Safety endpoints were hemorrhagic episodes and death.The prevalence of neurologic deterioration and recurrent ischemic stroke were lower in patients in the combination therapy group than in those of the monotherapy group (3.52% versus 9.78% and 1.76% versus 6.29%, respectively). At day 30 of treatment, the platelet aggregations and platelet-leukocyte aggregates were lower in patients who were treated with clopidogrel and aspirin than in patients given aspirin alone (P < .001).For patients with acute large-artery atherosclerosis stroke, treatment with clopidogrel and aspirin for 1 month provided significantly greater inhibition of platelet activity than aspirin alone. Thus, dual therapy can be safer and more effective in reducing ischemic stroke recurrence and neurologic deterioration.