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Shock (Augusta, Ga.) Jan 2017The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury.
METHODS
We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. Medline, embase, and cochrane databases were searched.
RESULTS
The literature search yielded 1,314 unique articles. Fifteen preclinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g., ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps, and prostaglandins. High-dose ASA may be the drug of choice. A meta-analysis of three clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36-0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality.
CONCLUSION
This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models are being evaluated to guide optimal timing and dose, before prospective randomized trials.
Topics: Animals; Aspirin; Humans; Platelet Activation; Respiratory Distress Syndrome
PubMed: 27984533
DOI: 10.1097/SHK.0000000000000745 -
Journal of the American Heart... May 2016A growing body of evidence suggests that atrial fibrillation (AF) is associated with myocardial infarction (MI). However, incidence and management of MI in AF is still... (Review)
Review
BACKGROUND
A growing body of evidence suggests that atrial fibrillation (AF) is associated with myocardial infarction (MI). However, incidence and management of MI in AF is still undefined.
METHODS AND RESULTS
We searched MEDLINE via PubMed and Cochrane database between 1965 and 2015. All observational clinical studies and interventional trials reporting 1-year incidence of MI in AF were included. We also discussed pathophysiological mechanisms, predictors, and therapeutic approaches to reduce the risk of MI in AF. Twenty-one observational studies and 10 clinical trials were included. The annual rate of MI in observational studies including AF patients ranged from 0.4% to 2.5%. Higher rates of MI were reported in AF patients with stable coronary artery disease (11.5%/year), vascular disease (4.47%/year), heart failure (2.9%/year), and in those undergoing coronary artery interventions (6.3%/year). However, lower annual rates have been described in AF patients from Eastern countries (0.2-0.3%/year), and in those enrolled in clinical trials (from 0.4 to 1.3%/year).
CONCLUSIONS
AF patients had a significant residual risk of MI despite anticoagulant treatment. Coexistence of atherosclerotic risk factors and platelet activation account for the increased risk of MI in AF. Identification of high-risk AF patients is a needed first step to develop cost-effective approaches for prevention. A new score, the 2MACE score, has been recently developed to stratify MI risk in AF, and may help not only in allocating resources to high-risk groups, but also in design of studies examining novel therapies for prevention of MI in AF.
Topics: Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Heart Failure; Humans; Incidence; Myocardial Infarction; Myocardial Revascularization; Risk Factors; Vascular Diseases
PubMed: 27208001
DOI: 10.1161/JAHA.116.003347 -
Journal of Thrombosis and Haemostasis :... Jun 2015Left ventricular assist devices (LVADs) have dramatically increased the survival of adults with end-stage systolic heart failure. However, rates of bleeding and... (Review)
Review
BACKGROUND
Left ventricular assist devices (LVADs) have dramatically increased the survival of adults with end-stage systolic heart failure. However, rates of bleeding and thromboembolism remain high.
OBJECTIVES
We completed a systematic review to evaluate outcomes of adults with LVADs treated with various anticoagulant and antiplatelet strategies.
METHODS
Databases were searched using the terms 'assist device', 'thrombosis', and 'anticoagulant' or 'platelet aggregation inhibitor' with appropriate synonyms, device names and manufacturers.
RESULTS AND CONCLUSIONS
Of 977 manuscripts, 24 articles met the inclusion criteria of adults with implanted LVADs where clinical outcomes were defined based on anticoagulant and/or antiplatelet regimen. Most studies reported treatment with unfractionated heparin post-operatively which was transitioned to a vitamin K antagonist (VKA). Goal INR varied between 1.5-3.5. Antiplatelet regimens ranged from no treatment to dual therapy. Definition of major bleeding differed between trials and incidence varied between 0% and 58%. The available evidence could not demonstrate a clear benefit of aspirin compared with VKA therapy alone [stroke RR 1.02 (95% CI 0.49-2.1)]. There was a suggestion that treatment with aspirin and dipyridamole decreased the risk of thromboembolism compared to aspirin [RR 0.50 (0.36-0.68)], but the comparison is limited by differences in demographics, devices, and INR goals among studies. Additionally, most studies did not blind investigators to outcomes thus contributing to an increased risk for bias. Clinical equipoise exists as to the most appropriate antithrombotic therapy in LVAD patients. Randomization between regimens within a prospective trial is needed to define the treatment regimen that minimizes both bleeding and thrombotic complications.
Topics: Anticoagulants; Blood Coagulation; Chi-Square Distribution; Drug Monitoring; Fibrinolytic Agents; Heart Failure; Heart-Assist Devices; Hemorrhage; Humans; International Normalized Ratio; Odds Ratio; Platelet Aggregation; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prosthesis Design; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; Ventricular Function, Left
PubMed: 25845489
DOI: 10.1111/jth.12948 -
Journal of Thrombosis and Haemostasis :... Jun 2015Ticagrelor and prasugrel have shown superiority over clopidogrel. However, it remains unclear if one is superior to another regarding on-treatment platelet reactivity. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ticagrelor and prasugrel have shown superiority over clopidogrel. However, it remains unclear if one is superior to another regarding on-treatment platelet reactivity.
OBJECTIVES
To compare the impact of ticagrelor and prasugrel on high on-treatment platelet reactivity (HTPR).
METHODS
The PubMed and Cochrane databases were searched for eligible studies in December 2014. Studies were eligible if they compared ticagrelor and prasugrel regarding high on-treatment platelet reactivity (HTPR). Pooled estimates were calculated by using a random-effects model with 95% confidence intervals.
RESULTS
We included 14 studies and 1822 patients: 805 and 1017 in the ticagrelor and prasugrel groups, respectively. The rate of HTPR was significantly lower in the ticagrelor group: 1.5% vs. 9.8% (RR = 0.27 [0.14-0.50]). The pre-specified analysis focusing on randomized trials (n = 10) showed consistent results (RR = 0.27 [0.12-0.60]).
CONCLUSION
Our results suggest that ticagrelor allows a higher platelet reactivity inhibition as compared with prasugrel and leads to a further decrease in the rate of HTPR.
Topics: Adenosine; Blood Platelets; Chi-Square Distribution; Drug Resistance; Heart Diseases; Humans; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Risk Factors; Ticagrelor; Treatment Outcome
PubMed: 25809392
DOI: 10.1111/jth.12907 -
Circulation. Cardiovascular Quality and... Jan 2015Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular... (Meta-Analysis)
Meta-Analysis Review
Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.
BACKGROUND
Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients.
METHODS AND RESULTS
We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole.
CONCLUSIONS
Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted.
Topics: Angina, Unstable; Cardiovascular Diseases; Drug Interactions; Drug Therapy, Combination; Evidence-Based Medicine; Gastrointestinal Hemorrhage; Humans; Myocardial Infarction; Observational Studies as Topic; Odds Ratio; Platelet Aggregation; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 25587094
DOI: 10.1161/CIRCOUTCOMES.114.001177 -
The Cochrane Database of Systematic... Oct 2014Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with intermittent claudication have a three- to six-fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007.
OBJECTIVES
To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication.
SEARCH METHODS
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9).
SELECTION CRITERIA
Double-blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta-analysis as a fixed-effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data.
MAIN RESULTS
We included fifteen double-blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta-analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta-analysis, for initial claudication distance (ICD - the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD - the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI -43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI.There was no association between treatment type and all-cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups.
AUTHORS' CONCLUSIONS
Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all-cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study.
Topics: Aged; Cilostazol; Humans; Intermittent Claudication; Middle Aged; Myocardial Infarction; Pentoxifylline; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Tetrazoles; Walking
PubMed: 25358850
DOI: 10.1002/14651858.CD003748.pub4 -
British Journal of Clinical Pharmacology Nov 2014Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect... (Meta-Analysis)
Meta-Analysis Review
AIMS
Platelets play an important role in cardiovascular disease, and β-blockers are often prescribed for cardiovascular disease prevention. β-Blockers may directly affect platelet aggregation, because β-adrenergic receptors are present on platelets. There is uncertainty about the existence and magnitude of an effect of β-blockers on platelet aggregation. The aim of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on platelet aggregation.
METHODS
MEDLINE and EMBASE were searched until April 2014. Two reviewers independently performed data extraction and risk of bias assessment. Type of β-blocker, population, treatment duration and platelet aggregation were extracted. Standardized mean differences were calculated for each study and pooled in a random-effects meta-analysis.
RESULTS
We retrieved 31 studies (28 clinical trials and three observational studies). β-Blockers decreased platelet aggregation (standardized mean difference -0.54, 95% confidence interval -0.85 to -0.24, P < 0.0001). This corresponds to a reduction of 13% (95% confidence interval 8-17%). Nonselective lipophilic β-blockers decreased platelet aggregation more than selective nonlipophilic β-blockers.
CONCLUSIONS
Clinically used β-blockers significantly reduce platelet aggregation. Nonselective lipophilic β-blockers seem to reduce platelet aggregation more effectively than selective nonlipophilic β-blockers. These findings may help to explain why some β-blockers are more effective than others in preventing cardiovascular disease.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Observational Studies as Topic; Platelet Aggregation
PubMed: 24730697
DOI: 10.1111/bcp.12404 -
Journal of Thrombosis and Haemostasis :... May 2014Antiplatelet therapy is the standard treatment for the prevention of cardiovascular events (CVEs). High on-treatment platelet reactivity (HPR) is a risk factor for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antiplatelet therapy is the standard treatment for the prevention of cardiovascular events (CVEs). High on-treatment platelet reactivity (HPR) is a risk factor for secondary CVEs in patients prescribed aspirin and/or clopidogrel. The present review and meta-analysis was aimed at assessing the ability of individual platelet-function tests to reliably identify patients at risk of developing secondary CVEs.
METHODS AND RESULTS
A systematic literature search was conducted to identify studies on platelet-reactivity measurements and CVEs. The main inclusion criteria were: (i) prospective study design; (ii) study medication, including aspirin and/or clopidogrel; and (iii) a platelet-function test being performed at baseline, before follow-up started. Of 3882 identified studies, 102 (2.6%; reporting on 44 098 patients) were included in the meta-analysis. With regard to high on-aspirin platelet reactivity (HAPR), 22 different tests were discussed in 55 studies (22 441 patients). Pooled analysis showed that HAPR was diagnosed in 22.2% of patients, and was associated with an increased CVE risk (relative risk [RR] 2.09; 95% confidence interval [CI] 1.77-2.47). Eleven HAPR tests independently showed a significantly increased CVE risk in patients with HAPR as compared with those with normal on-aspirin platelet reactivity. As regards high on-clopidogrel platelet reactivity (HCPR), 59 studies (34 776 patients) discussed 15 different tests, and reported that HCPR was present in 40.4% of patients and was associated with an increased CVE risk (RR 2.80; 95% CI 2.40-3.27). Ten tests showed a significantly increased CVE risk.
CONCLUSIONS
Patients with HPR are suboptimally protected against future cardiovascular complications. Furthermore, not all of the numerous platelet tests proved to be able to identify patients at increased cardiovascular risk.
Topics: Aspirin; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Risk Factors; Ticlopidine
PubMed: 24612413
DOI: 10.1111/jth.12538 -
British Journal of Clinical Pharmacology Mar 2014The PlA1/A2 polymorphism of glycoprotein IIIa (GPIIIa) has been associated with both antiplatelet drug resistance and increased cardiovascular events. The aim of this... (Meta-Analysis)
Meta-Analysis Review
AIM
The PlA1/A2 polymorphism of glycoprotein IIIa (GPIIIa) has been associated with both antiplatelet drug resistance and increased cardiovascular events. The aim of this study was to conduct the first meta-analysis investigating the association between carriage of the PlA2 allele and resistance to currently licensed antiplatelet drugs.
METHODS
Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where antiplatelet resistance was measured using validated techniques, pooled odds ratios (ORs) were calculated using fixed effects and random effects models.
RESULTS
Sixteen studies were eligible for statistical analysis and included 1650 PlA1 homozygous subjects and 668 carriers of the PlA2 allele. For carriers of the PlA2 allele, OR 0.924 (n = 2318; 95% CI 0.743, 1.151; P = 0.481) was observed for resistance to any antiplatelet drug, OR 0.862 (n = 2085; 95% CI 0.685, 1.086; P = 0.208) for resistance to aspirin and OR 1.429 (n = 233; 95% CI 0.791, 2.582; P = 0.237) for resistance to clopidogrel. In the aspirin cohort, sub-group analysis revealed no statistical association in either healthy subjects or those with cardiovascular disease. PlA2 carriage was marginally associated with aspirin sensitivity using the fixed effects model when identified by the PFA-100 assay (n = 1151; OR 0.743, 95% CI 0.558, 0.989; P = 0.041) but with significant heterogeneity (I(2) = 55%; P = 0.002). Significance was lost with analysis using a random effects model.
CONCLUSIONS
The totality of published data does not support an association between carriage of the PlA2 allele and antiplatelet drug resistance. Significant heterogeneity indicates the need for larger studies using validated and standardized assays.
Topics: Drug Resistance; Gene Frequency; Genotype; Humans; Integrin beta3; Odds Ratio; Phenotype; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Polymorphism, Genetic; Risk Factors
PubMed: 23834376
DOI: 10.1111/bcp.12204 -
Clinical Cardiology Apr 2013There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute coronary syndrome. Most pharmacokinetic and pharmacodynamic studies in vivo were conducted using small sample sizes and were single centered, resulting in conflicting data.
HYPOTHESIS
PPIs may attenuate the antiplatelet effect of clopidogrel in vivo and lead to an increased risk of cardiovascular events.
METHODS
PubMed, the Cochrane Library, Embase, Web of Science, and China Biology Medicine Disc were searched. Randomized controlled trials that compared pharmacodynamic impacts of a PPI on the efficacy of clopidogrel in vivo were included. Two independent reviewers evaluated study quality and extracted data for meta-analysis.
RESULTS
We identified 8 eligible studies. Compared to clopidogrel treatment alone, patients who received both a PPI and clopidogrel had less of a decrease in the platelet reactivity index (weighted mean difference [WMD]: 8.18; 95% confidence interval [CI]: 6.81-9.56; P<0.00001), less adenosine 5'-diphosphate-induced platelet aggregation inhibition (WMD: 7.28; 95% CI: 2.44-12.11; P=0.003), higher P2Y12 reaction units (WMD: 40.58; 95% CI: 19.31-61.86; P=0.0002), and higher risks of clopidogrel resistance (odds ratio [OR]: 2.49; 95% CI: 1.49-4.14; P=0.0005). There were no significant differences, however, for the incidences of major adverse cardiovascular events between the 2 groups (OR: 1.07; 95% CI: 0.44-2.59; P=0.88), and treatment with a PPI and clopidogrel significantly reduced the risk of adverse gastrointestinal events (OR: 0.16; 95% CI: 0.04-0.62; P=0.008).
CONCLUSIONS
Concomitant use of a PPI with clopidogrel attenuated the antiplatelet effect of clopidogrel, but may be clinically unimportant because there were no clinical differences in the risk for major adverse cardiovascular events.
Topics: Adenosine Diphosphate; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Drug Interactions; Drug Resistance; Gastrointestinal Diseases; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Receptors, Purinergic P2Y12; Ticlopidine
PubMed: 23450832
DOI: 10.1002/clc.22094