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PloS One 2014Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse. (Meta-Analysis)
Meta-Analysis Review
Impact of ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose and treatment response in patients with opioid addiction: a systematic review and meta-analysis.
BACKGROUND
Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse.
OBJECTIVES
To determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment).
METHODS
Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the CYP2B6*6 or ABCB1 polymorphisms.
RESULTS
We screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in CYP2B6*6 homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05-1.00, p = 0.03) with minimal heterogeneity (I(2) = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27-2.61, p = 0.02) however significant heterogeneity was observed (I(2) = 69%). Carriers of the CYP2B6*6 haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the ABCB1 polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response.
CONCLUSION
Although the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the CYP2B6*6 genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Analgesics, Opioid; Aryl Hydrocarbon Hydroxylases; Biotransformation; Cytochrome P-450 CYP2B6; Databases, Bibliographic; Drug Administration Schedule; Drug Monitoring; Haplotypes; Homozygote; Humans; Methadone; Opioid-Related Disorders; Polymorphism, Genetic
PubMed: 24489693
DOI: 10.1371/journal.pone.0086114 -
Phytomedicine : International Journal... May 2018Fuzi, which is the processed lateral roots of Aconitum carmichaeli Debx. (Ranunculaceae), is a traditional herbal medicine that is well known for its excellent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fuzi, which is the processed lateral roots of Aconitum carmichaeli Debx. (Ranunculaceae), is a traditional herbal medicine that is well known for its excellent pharmacological effects and acute toxicity. Aconitum alkaloids are responsible for its pharmacological activity and toxicity. Although a large number of studies on Fuzi have been reported, no comprehensive review on its pharmacokinetics has yet been published.
PURPOSE
This paper seeks to present a comprehensive review regarding the phytochemistry, pharmacokinetic features and toxicity of Fuzi. The regulation of drug-metabolizing enzymes (DMEs) and efflux transporters (ETs) by Fuzi is also concluded. Additionally, the use of Fuzi as a personalized medicine based on the bioavailability barrier (BB), which mainly comprises DMEs and ETs, is discussed.
METHODS
All available information on Fuzi was collected by searching for key words in PubMed, ScienceDirect, CNKI, Google Scholar, Baidu Scholar, and Web of Science.
RESULTS
Aconitum alkaloids, which mainly include diester-diterpene alkaloids (DDAs), monoester-diterpene alkaloids (MDAs) and unesterified-diterpene alkaloids (UDAs), could be detected after Fuzi ingestion in vivo. The Aconitum alkaloids are rapidly absorbed in the intestine and extensively distributed in the body. DMEs, especially CYP3A4/5, are responsible for various types of metabolic reactions of the Aconitum alkaloids. ETs, including P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP), are involved in the efflux of the DDAs and MDAs. The kidney is the most important organ involved in the excretion of the Aconitum alkaloids. DDAs are the main toxic compounds present in Fuzi, and their acute toxicity is mainly due to their effects on the voltage-dependent sodium channels. Furthermore, Fuzi can substantially regulate DMEs and ETs.
CONCLUSIONS
The toxicity of DDAs is acute. However, further investigations are necessary to determine the exact toxicological mechanisms. The significant impact of Fuzi on DMEs and ETs suggests that the co-administration of Fuzi with drugs that are substrates of DMEs and/or ETs may cause herb-drug interactions (HDIs). The BB network controlled exposure to the Aconitum alkaloids in vivo. Polymorphisms of DMEs and ETs in different individuals contribute to the differences in the efficacy and toxicity of Fuzi ingestion. In the future, the use of Fuzi as personalized medicine based on the BB network is necessary and practical to achieve ideal therapeutic efficacy with minimal toxicity.
Topics: Aconitum; Alkaloids; Animals; Biological Availability; Chromatography, High Pressure Liquid; Diterpenes; Drugs, Chinese Herbal; Herb-Drug Interactions; Humans; Inactivation, Metabolic; Phytotherapy; Plant Extracts; Precision Medicine; Tissue Distribution
PubMed: 29526584
DOI: 10.1016/j.phymed.2018.03.001 -
PloS One 2024An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful... (Meta-Analysis)
Meta-Analysis
Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.
An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp.
Topics: Rats; Animals; Blood-Brain Barrier; Vascular Endothelial Growth Factor A; Matrix Metalloproteinase 9; Electroacupuncture; Rats, Sprague-Dawley; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily B; Permeability
PubMed: 38536776
DOI: 10.1371/journal.pone.0298533 -
Drug Resistance Updates : Reviews and... May 2020Multidrug resistance (MDR) is the dominant cause of the failure of cancer chemotherapy. The design of antitumor drugs that are able to evade MDR is rapidly evolving,...
Multidrug resistance (MDR) is the dominant cause of the failure of cancer chemotherapy. The design of antitumor drugs that are able to evade MDR is rapidly evolving, showing that this area of biomedical research attracts great interest in the scientific community. The current review explores promising recent approaches that have been developed with the aim of circumventing or overcoming MDR. Encouraging results have been obtained in the investigation of the MDR-modulating properties of various classes of natural compounds and their analogues. Inhibition of P-gp or downregulation of its expression have proven to be the main mechanisms by which MDR can be surmounted. The use of hybrid molecules that are able to simultaneously interact with two or more cancer cell targets is currently being explored as a means to circumvent drug resistance. This strategy is based on the design of hybrid compounds that are obtained either by merging the structural features of separate drugs, or by conjugating two drugs or pharmacophores via cleavable/non-cleavable linkers. The approach is highly promising due to the pharmacokinetic and pharmacodynamic advantages that can be achieved over the independent administration of the two individual components. However, it should be stressed that the task of obtaining successful multivalent drugs is a very challenging one. The conjugation of anticancer agents with nitric oxide (NO) donors has recently been developed, creating a particular class of hybrid that can combat tumor drug resistance. Appropriate NO donors have been shown to reverse drug resistance via nitration of ABC transporters and by interfering with a number of metabolic enzymes and signaling pathways. In fact, hybrid compounds that are produced by covalently attaching NO-donors and antitumor drugs have been shown to elicit a synergistic cytotoxic effect in a variety of drug resistant cancer cell lines. Another strategy to circumvent MDR is based on nanocarrier-mediated transport and the controlled release of chemotherapeutic drugs and P-gp inhibitors. Their pharmacokinetics are governed by the nanoparticle or polymer carrier and make use of the enhanced permeation and retention (EPR) effect, which can increase selective delivery to cancer cells. These systems are usually internalized by cancer cells via endocytosis and accumulate in endosomes and lysosomes, thus preventing rapid efflux. Other modalities to combat MDR are described in this review, including the pharmaco-modulation of acridine, which is a well-known scaffold in the development of bioactive compounds, the use of natural compounds as means to reverse MDR, and the conjugation of anticancer drugs with carriers that target specific tumor-cell components. Finally, the outstanding potential of in silico structure-based methods as a means to evaluate the ability of antitumor drugs to interact with drug transporters is also highlighted in this review. Structure-based design methods, which utilize 3D structural data of proteins and their complexes with ligands, are the most effective of the in silico methods available, as they provide a prediction regarding the interaction between transport proteins and their substrates and inhibitors. The recently resolved X-ray structure of human P-gp can help predict the interaction sites of designed compounds, providing insight into their binding mode and directing possible rational modifications to prevent them from becoming P-gp drug substrates. In summary, although major efforts were invested in the search for new tools to combat drug resistant tumors, they all require further implementation and methodological development. Further investigation and progress in the abovementioned strategies will provide significant advances in the rational combat against cancer MDR.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP-Binding Cassette Transporters; Acridines; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Drug Design; Drug Resistance, Neoplasm; Glycoconjugates; Humans; Nanoparticles; Neoplasms; Nitric Oxide; Plant Preparations; Polymers; Technology, Pharmaceutical
PubMed: 32087558
DOI: 10.1016/j.drup.2020.100682 -
Current Cancer Drug Targets May 2009A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship... (Review)
Review
A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship between cisplatin and paclitaxel. Here we systematically review genetically modified cell lines in which the inverse cisplatin/paclitaxel resistance phenotype has resulted. This will form a short list of genes which may play a role in the mechanism of the inverse resistance relationship as well as act as potential markers for monitoring the development of resistance in the clinical treatment of cancer. The literature search revealed 91 genetically modified cell lines which report toxicity or viability/apoptosis data for cisplatin and paclitaxel relative to their parental cell lines. This resulted in 26 genes being associated with the inverse cisplatin/paclitaxel phenotype. The gene with the highest number of genetically modified cell lines associated with the inverse resistance relationship was BRCA1 and this gene is discussed in detail with reference to chemotherapy response in cell lines and in the clinical treatment of breast, ovarian and lung cancer. Other genes associated with the inverse resistance phenotype included dihydrodiol dehydrogenase (DDH) and P-glycoprotein. Genes which caused cross resistance or cross sensitivity between cisplatin and paclitaxel were also examined, the majority of these genes were apoptosis associated genes which may be useful for predicting cross resistance. We propose that BRCA1 should be the first of a panel of cellular markers to predict the inverse cisplatin/paclitaxel resistance phenotype.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Antineoplastic Agents; BRCA1 Protein; Cell Line, Tumor; Cisplatin; Female; Genes, BRCA1; Humans; Neoplasms; Oxidoreductases; Paclitaxel; Phenotype; Treatment Outcome
PubMed: 19442054
DOI: 10.2174/156800909788166592 -
Clinical Pharmacokinetics Sep 2021Patients affected by poverty-related infectious diseases (PRDs) are disproportionally affected by malnutrition. To optimize treatment of patients affected by PRDs, we...
BACKGROUND
Patients affected by poverty-related infectious diseases (PRDs) are disproportionally affected by malnutrition. To optimize treatment of patients affected by PRDs, we aimed to assess the influence of malnutrition associated with PRDs on drug pharmacokinetics, by way of a systematic review.
METHODS
A systematic review was performed on the effects of malnourishment on the pharmacokinetics of drugs to treat PRDs, including HIV, tuberculosis, malaria, and neglected tropical diseases.
RESULTS
In 21/29 PRD drugs included in this review, pharmacokinetics were affected by malnutrition. Effects were heterogeneous, but trends were observed for specific classes of drugs and different types and degrees of malnutrition. Bioavailability of lumefantrine, sulfadoxine, pyrimethamine, lopinavir, and efavirenz was decreased in severely malnourished patients, but increased for the P-glycoprotein substrates abacavir, saquinavir, nevirapine, and ivermectin. Distribution volume was decreased for the lipophilic drugs isoniazid, chloroquine, and nevirapine, and the α1-acid glycoprotein-bound drugs quinine, rifabutin, and saquinavir. Distribution volume was increased for the hydrophilic drug streptomycin and the albumin-bound drugs rifampicin, lopinavir, and efavirenz. Drug elimination was decreased for isoniazid, chloroquine, quinine, zidovudine, saquinavir, and streptomycin, but increased for the albumin-bound drugs quinine, chloroquine, rifampicin, lopinavir, efavirenz, and ethambutol. Clinically relevant effects were mainly observed in severely malnourished and kwashiorkor patients.
CONCLUSIONS
Malnutrition-related effects on pharmacokinetics potentially affect treatment response, particularly for severe malnutrition or kwashiorkor. However, pharmacokinetic knowledge is lacking for specific populations, especially patients with neglected tropical diseases and severe malnutrition. To optimize treatment in these neglected subpopulations, adequate pharmacokinetic studies are needed, including severely malnourished or kwashiorkor patients.
Topics: HIV Infections; Humans; Malaria; Malnutrition; Nevirapine; Pharmaceutical Preparations; Poverty
PubMed: 34060020
DOI: 10.1007/s40262-021-01031-z -
Journal of Nuclear Medicine : Official... Mar 2009Multidrug resistance (MDR) is a major problem in lung cancer. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been demonstrated to be a noninvasive marker for the... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Multidrug resistance (MDR) is a major problem in lung cancer. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been demonstrated to be a noninvasive marker for the diagnosis of MDR-related P glycoprotein and MDR-associated protein expression in various solid tumors. Studies have shown that (99m)Tc-MIBI could play a significant role in the management of lung cancer; for example, it could be used in the selection of patients for chemotherapy or radiotherapy or in combined protocols before the start of treatment. Accurate selection of chemosensitive patients with (99m)Tc-MIBI would result not only in effective treatment of patients but also in significant cost savings for health care providers. There is increasing pressure on health care providers to consider costs in medical decision making, particularly in the last decade, as several economic evaluations have appeared in the medical literature. The aims of this study were to undertake a systematic review of the performance of (99m)Tc-MIBI imaging in the assessment of treatment resistance in lung cancer and to use the findings of the review in a decision tree analysis of the potential cost-effectiveness of (99m)Tc-MIBI imaging in selecting lung cancer patients for chemotherapy.
METHODS
This study included a systematic review of the literature and a meta-analysis together with a cost-effectiveness analysis of studies with a decision tree analysis model.
RESULTS
Analysis of the studies revealed that the overall sensitivity of (99m)Tc-MIBI in identifying responders to chemotherapy was 94%, the specificity was 90%, and the accuracy was 92%. The sensitivity analysis revealed an incremental cost-effectiveness ratio of greater than pound30,000 ( approximately $42,900) for the strategy of treating all patients to recover the small loss of life expectancy (7.5 d) associated with the use of (99m)Tc-MIBI to preselect patients for chemotherapy.
CONCLUSION
(99m)Tc-MIBI SPECT can accurately predict which patients with lung cancer will respond to chemotherapy. The use of (99m)Tc-MIBI to preselect patients for chemotherapy has the potential to yield significant cost savings in the health care system without a significant loss of life expectancy for patients.
Topics: Cost-Benefit Analysis; Decision Trees; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon; Treatment Outcome
PubMed: 19223414
DOI: 10.2967/jnumed.108.055988 -
Thrombosis Research Oct 2020Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous... (Review)
Review
BACKGROUND
Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous thrombosis. Due to their novelty, pharmacokinetic DOAC drug-drug interactions (DDIs) that result in clinical adverse events have not been well-documented.
OBJECTIVE
This study aims to systematically review reported pharmacokinetic DDIs resulting in clinical adverse events through documented observational evidence to better inform clinicians in clinical practice.
METHODS
A comprehensive literature review of EMBASE, MEDLINE, and Ovid HealthStar was conducted through March 10th, 2020. Two independent reviewers screened and extracted data from eligible articles according to pre-established inclusion and exclusion criteria. Articles reporting bleeding or thrombotic outcomes in non-controlled (observational) settings resulting from suggested pharmacokinetic DOAC DDIs were included.
RESULTS
A total of 5567 citations were reviewed, of which 24 were included following data extraction. The majority were case reports (n = 21) documenting a single adverse event resulting from a suspected DOAC DDI, while the remaining papers were a case series (n = 1) and cohort studies (n = 2). The most commonly reported interacting drugs were amiodarone and ritonavir (bleeding), and phenobarbital, phenytoin, and carbamazepine (thrombosis). Bleeding events more often resulted from a combined mechanism (P-glycoprotein AND CYP3A4 inhibition), whereas thrombotic events resulted from either combined OR single P-glycoprotein/CYP3A4 induction.
CONCLUSION
Current literature evaluating the real-world risk of DOAC DDIs is limited to few case reports and retrospective observational analyses. Clinicians are encouraged to continue to report suspected drug interactions resulting in adverse events.
Topics: Administration, Oral; Anticoagulants; Drug Interactions; Hemorrhage; Humans; Observational Studies as Topic; Pharmaceutical Preparations; Retrospective Studies
PubMed: 33213849
DOI: 10.1016/j.thromres.2020.08.016 -
The American Journal of Medicine May 2018Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome...
BACKGROUND
Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. Direct oral anticoagulant levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors, such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug-drug interaction by the concomitant use of DOACs and amiodarone.
METHODS
We performed a systematic review of MEDLINE, the Cochrane Central Register of Clinical Trials, and Embase, limiting our search to randomized controlled trials of patients with atrial fibrillation that have compared DOACs versus warfarin for prophylaxis of stroke or systemic embolism, to analyze the impact on stroke or systemic embolism, major bleeding, and intracranial bleeding risk in patients with concomitant use of amiodarone. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method. The fixed effects model was used owing to heterogeneity (I) < 25%.
RESULTS
Four trials with a total of 71,683 patients were analyzed, from which 5% of patients (n = 3212) were concomitantly taking DOAC and amiodarone. We found no statistically significant difference for any of the clinical outcomes (stroke or systemic embolism [RR 0.85; 95% CI, 0.67-1.06], major bleeding [RR 0.91; 95% CI, 0.77-1.07], or intracranial bleeding [RR 1.10; 95% CI, 0.68-1.78]) among patients taking DOAC and amiodarone versus DOAC without amiodarone.
CONCLUSION
On the basis of the results of this meta-analysis, co-administration of DOACs and amiodarone, a dual P-gp/CYP3A4 inhibitor, does not seem to affect efficacy or safety outcomes in patients with atrial fibrillation.
Topics: Administration, Oral; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Drug Interactions; Drug Therapy, Combination; Hemorrhage; Humans; Randomized Controlled Trials as Topic
PubMed: 29274758
DOI: 10.1016/j.amjmed.2017.11.047 -
Expert Opinion on Drug Safety Dec 2020The effects of the C3435T genetic polymorphism on clopidogrel responses are conflicting and inconclusive especially in patients undergoing percutaneous coronary... (Meta-Analysis)
Meta-Analysis
Effects of the C3435T single nucleotide polymorphism on major adverse cardiovascular events in acute coronary syndrome or coronary artery disease patients undergoing percutaneous coronary intervention and treated with clopidogrel: A systematic review and meta-analysis.
INTRODUCTION
The effects of the C3435T genetic polymorphism on clopidogrel responses are conflicting and inconclusive especially in patients undergoing percutaneous coronary intervention (PCI). This study examined the pooled risk of major adverse cardiovascular events (MACE) and bleeding events associated with the C3435T polymorphism in acute coronary syndrome or coronary artery disease patients undergoing PCI and treated with clopidogrel.
AREAS COVERED
Literature was searched in different resources for eligible studies. The pooled risk ratio was measured using RevMan software, with <0.05 (two-sided) set as statistically significant.
EXPERT OPINION
The C3435T homozygous mutant (TT) was associated with significantly increased risk of MACE compared to either wild type genotype (CC) or the combination of wild type and heterozygous genotypes (TT vs. CC: RR 1.33; 95% CI 1.06-1.68; =0.02; TT vs. CC+CT: RR 1.32; 95% CI 1.10-1.60; =0.004). Safety outcomes, i.e. bleeding events were not significantly different between the genetic models investigated (TT vs. CC: RR 1.93; 95% CI 0.86-4.35; =0.11; TT vs. CC+CT: RR 1.36; 95% CI 0.89-2.09; =0.16; CT+TT vs. CC: RR 1.20; 95% CI 0.59-2.44; =0.61). It is suggested that C3435T genotype should be tested for ACS/CAD patients undergoing PCI to ensure optimum therapy of clopidogrel.
Topics: ATP Binding Cassette Transporter, Subfamily B; Acute Coronary Syndrome; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Genotype; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymorphism, Single Nucleotide
PubMed: 33040624
DOI: 10.1080/14740338.2020.1836152