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Effects of the ABCB1 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

Biswas M, Rahaman S, Biswas TK, Ibrahim B

Expert Opin Drug Saf, 2020 Dec;19(12):1605-1616.
PMID: 33040624 DOI: 10.1080/14740338.2020.1836152

INTRODUCTION: The effects of the ABCB1 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 ABCB1 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 p<0.05 (two-sided) set as statistically significant.
EXPERT OPINION: The ABCB1 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; p=0.02; TT vs. CC+CT: RR 1.32; 95% CI 1.10-1.60; p=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; p=0.11; TT vs. CC+CT: RR 1.36; 95% CI 0.89-2.09; p=0.16; CT+TT vs. CC: RR 1.20; 95% CI 0.59-2.44; p=0.61). It is suggested that ABCB1 C3435T genotype should be tested for ACS/CAD patients undergoing PCI to ensure optimum therapy of clopidogrel.
Risk of major adverse cardiovascular events for concomitant use of clopidogrel and proton pump inhibitors in patients inheriting CYP2C19 loss-of-function alleles: meta-analysis

Biswas M, Rahaman S, Biswas TK, Ibrahim B

Int J Clin Pharm, 2021 Oct;43(5):1360-1369.
PMID: 33774763 DOI: 10.1007/s11096-021-01261-y

Background Efficacy of clopidogrel may be diminished due to either co-administration of proton pump inhibitors or carrying CYP2C19 loss-of-function alleles. However, patients may be at greater risk of major adverse cardiovascular events if taking clopidogrel together with proton pump inhibitors and also inherited the CYP2C19 loss-of-function alleles which may cause further reduction of clopidogrel efficacy. This is due to the cumulative effects of drug-drug interactions and drug-gene interactions collectively referred to as multifactorial drug-gene interactions. Aim of the review The aim of this analysis was to estimate aggregated risk of major adverse cardiovascular events for either coronary heart disease or stroke patients with multifactorial drug-gene interactions versus clopidogrel alone with or without drug-gene interactions. Methods Literatures were searched using different resources based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using RevMan software following either fixed/random effects model based on the levels of heterogeneity. A p value
Risk of major adverse cardiovascular events of CYP2C19 loss-of-function genotype guided prasugrel/ticagrelor vs clopidogrel therapy for acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis

Biswas M, Kali MSK, Biswas TK, Ibrahim B

Platelets, 2021 Jul 04;32(5):591-600.
PMID: 32664772 DOI: 10.1080/09537104.2020.1792871

The most effective antiplatelet treatments for acute coronary syndrome (ACS) patients carrying CYP2C19 loss-of-function (LoF) alleles undergoing percutaneous coronary intervention (PCI) is still debating and conflicting. It was aimed to compare the efficacy and safety endpoints for these patients treated with alternative P2Y12 receptor blockers (e.g. prasugrel or ticagrelor) against clopidogrel. Literature was searched in PubMed, Cochrane library, Synapse and 1000 Genomes databases following PRISMA guidelines for identifying relevant studies. Aggregated risk was estimated by RevMan software using either fixed/random-effects models where P values<0.05 (two-sided) were considered statistically significant. Nine studies comprising 16,132 ACS patients undergoing PCI were included in this analysis in which 2,746 and 2,640 patients were in the CYP2C19 LoF clopidogrel and alternatives treatment group, respectively. It was demonstrated that patients treated with prasugrel or ticagrelor significantly reduced the risk of MACEs (RR 0.58; 95% CI 0.45-0.76; P<0.0001) as compared to patients with clopidogrel where both groups carrying CYP2C19 LoF alleles. Subgroup analysis showed that prasugrel or ticagrelor significantly reduced the risk of cardiovascular death (RR 0.44; 95% CI: 0.25-0.74; P=0.002) and MI (RR 0.60; 95% CI: 0.44-0.81; P=0.0008) while other clinical outcomes were not found statistically significant between these two groups; stroke (RR 0.77; 95% CI: 0.43-1.38; P =0.39), stent thrombosis (RR 0.67; 95% CI: 0.38-1.18; P =0.17), unstable angina (RR 0.55; 95% CI: 0.13-2.33; P =0.42), revascularisation (RR 0.79; 95% CI: 0.28-2.24; P=0.66). Bleeding events were not found significantly different between these groups (RR 1.06; 95% CI: 0.88-1.28; P=0.55). Considering efficacy and safety, alternative antiplatelets (e.g. prasugrel or ticagrelor) may be regarded as better treatment option as compared to clopidogrel for ACS patients undergoing PCI.
Fulltext Association of Sex, Age, and Comorbidities with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis

Biswas M, Rahaman S, Biswas TK, Haque Z, Ibrahim B

Intervirology, 2020 Dec 09.
PMID: 33296901 DOI: 10.1159/000512592

INTRODUCTION: Although severe acute respiratory syndrome coronavirus-2 infection is causing mortality in considerable proportion of coronavirus disease-2019 (COVID-19) patients, however, evidence for the association of sex, age, and comorbidities on the risk of mortality is not well-aggregated yet. It was aimed to assess the association of sex, age, and comorbidities with mortality in COVID-2019 patients.
METHODS: Literatures were searched using different keywords in various databases. Relative risks (RRs) were calculated by RevMan software where statistical significance was set as p < 0.05.
RESULTS: COVID-19 male patients were associated with significantly increased risk of mortality compared to females (RR 1.86: 95% confidence interval [CI] 1.67-2.07; p < 0.00001). Patients with age ≥50 years were associated with 15.4-folds significantly increased risk of mortality compared to patients with age <50 years (RR 15.44: 95% CI 13.02-18.31; p < 0.00001). Comorbidities were also associated with significantly increased risk of mortality; kidney disease (RR 4.90: 95% CI 3.04-7.88; p < 0.00001), cereborovascular disease (RR 4.78; 95% CI 3.39-6.76; p < 0.00001), cardiovascular disease (RR 3.05: 95% CI 2.20-4.25; p < 0.00001), respiratory disease (RR 2.74: 95% CI 2.04-3.67; p < 0.00001), diabetes (RR 1.97: 95% CI 1.48-2.64; p < 0.00001), hypertension (RR 1.95: 95% CI 1.58-2.40; p < 0.00001), and cancer (RR 1.89; 95% CI 1.25-2.84; p = 0.002) but not liver disease (RR 1.64: 95% CI 0.82-3.28; p= 0.16).
CONCLUSION: Implementation of adequate protection and interventions for COVID-19 patients in general and in particular male patients with age ≥50 years having comorbidities may significantly reduce risk of mortality associated with COVID-19.
Synthesis of new liquid crystals embedded gold nanoparticles for photoswitching properties

Rahman ML, Biswas TK, Sarkar SM, Yusoff MM, Yuvaraj AR, Kumar S

J Colloid Interface Sci, 2016 Jun 15;478:384-393.
PMID: 27341036 DOI: 10.1016/j.jcis.2016.06.039

A new series of liquid crystals decorated gold nanoparticles is synthesized whose molecular architecture has azobenzenes moieties as the peripheral units connected to gold nanoparticles (Au NPs) via alkyl groups. The morphology and mesomorphic properties were investigated by field emission scanning electron microscope, high-resolution transmission electron microscopy, differential scanning calorimetry and polarizing optical microscopy. The thiolated ligand molecules (3a-c) showed enantiotropic smectic A phase, whereas gold nanoparticles (5a-c) exhibit nematic and smectic A phase with monotropic nature. HR-TEM measurement showed that the functionalized Au NPs are of the average size of 2nm and they are well dispersed without any aggregation. The trans-form of azo compounds showed a strong band in the UV region at ∼378nm for the π-π(∗) transition, and a weak band in the visible region at ∼472nm due to the n-π(∗) transition. These molecules exhibit attractive photoisomerization behaviour in which trans-cis transition takes about 15s whereas the cis-trans transition requires about 45min for compound 5c. The extent of reversible isomerization did not decay after 10 cycles, which proved that the photo-responsive properties of 5c were stable and repeatable. Therefore, these materials may be suitably exploited in the field of molecular switches and the optical storage devices.