Influence of CYP450 Enzymes and ABCB1 Polymorphisms on Clopidogrel Response in Moroccan Patients with Acute Coronary Syndromes.

Introduction: Clopidogrel is an antiplatelet prodrug primarily prescribed to prevent or treat acute coronary syndrome (ACS) or acute ischemic stroke (IS), polymorphisms of genes encoding cytochrome P-450 (CYP) and P-glycoprotein transporter, could affect the efficiency of clopidogrel absorption and biotransformation, especially during the first critical hours following its administration. Methods: The present study was designed to investigate the potential association of clopidogrel responsiveness and 14 polymorphisms in the genes encoding the CYPs (CYP2C9, 2C19, 3A4, 3A5, 1A2, and 2B6), the ATP binding cassette subfamily B member 1 (ABCB1). Platelet aggregation activity was measured after 8h of 300mg clopidogrel administration for fifty-five ACS patients. Results: There was no significant association between polymorphism of the studied CYPs and clopidogrel responsiveness (P>0.05). The frequency of the ABCB1 3435 T allele in clopidogrel non-responders was higher (78.9%) compared to responders (52.8%), but this difference was not significant (P=0.057). Demographic characteristics, comorbidities, concomitant treatments were not associated with clopidogrel response. Discussion: There was no effect of the studied genetic variations and demographic factors on the platelet activity of clopidogrel in Moroccan ACS patients.

The national moroccan registry of ST-elevation myocardial infarction (MR-MI).

BACKGROUND: MR-MI is the first national Moroccan ST-elevation myocardial infarction (STEMI) registry. Its objectives are to assess patient management modalities and highlight the clinical and therapeutic characteristics of this pathology in all cardiology centres on a national scale. METHODS: Adult patients presenting with STEMI within 5 days of symptoms onset were enrolled over a period of 18 weeks from April to August 2018. 57 cardiology centres distributed in 22 cities in Morocco participated in the study, including 5 university hospitals, representing 70% of Moroccan centres managing STEMI patients. A case report form was sent to the investigators in both electronic and paper forms. Sociodemographic, clinical, management, revascularization, and follow-up data were collected. RESULTS: A total of 809 patients were recruited. The population was mostly male (74.8%) with an average age of 62.6 ± 11.6 years. The most common risk factors were smoking (38.3%) arterial hypertension (30.7%), and diabetes (28%). 30% of patients were admitted within the first 6 h of symptoms onset and early revascularization was performed on 49.6%. Mortality rate was 5.2% in-hospital and 3.2% at the one-month follow-up. CONCLUSION: MR-MI is the first Moroccan STEMI registry on a national scale. Relevant management delays are much longer than other countries, and less than 50% of the patients that present on time benefit from early revascularization. Efforts remain to be done on the optimal diagnosis and treatment of STEMI.

A synergic effect between CYP2C19*2, CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function alleles is associated with Clopidogrel resistance among Moroccan Acute Coronary Syndromes patients.

OBJECTIVE: The main objective of our study was to investigate the association of CYP2C19*2 and CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function variants of CYP2C19 gene with Clopidogrel resistance in a sample of Moroccan Acute Coronary Syndromes patients. RESULTS: Our results showed the existence of a synergic effect between the three alleles, statistically very significant, on Clopidogrel resistance among the treated patients (P = 0.0033). For the three variants of the CYP2C19 gene, the heterozygous and homozygous mutant genotypes were the most frequent among ACS patients (CYP2C19*2: 82.76% GA and 10.35% AA; CYP2C19*3: 76.67% GA and 18.33% AA; CYP2C19*17: 66.67% CT and 18.66% TT). Allelic frequencies were 51.73% vs 48.27% (P < 0.001); 56.67% vs 43.33% (P < 0.001); and 52% vs 48% (P = 0.01) for the mutant and wild type alleles of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 variants respectively. Our results support a role of CYP2C19 gene variants as a potential marker of Clopidogrel response. Understanding the functional and clinical consequences of these variants may help for treating patients more effectively, they could be genetically screened and appropriate dose adjustments could be made on the basis of their CYP2C19 genotype.

Does i-T744C P2Y12 Polymorphism Modulate Clopidogrel Response among Moroccan Acute Coronary Syndromes Patients?

Background. An interindividual variability in response to Clopidogrel has been widely described in patients with acute coronary syndromes (ACS). The contribution of genetics on modulating this response was widely discussed. The objective of our study was to investigate the potential effect of i-T744C P2Y12 polymorphism on Clopidogrel response in a sample of Moroccan ACS patients. We tried also to determine the frequency of this polymorphism among Moroccan ACS compared to healthy subjects. Methods and Results. 77 ACS patients versus 101 healthy controls were recruited. DNA samples were genotyped by PCR-RFLP method. The VerifyNow assay was used to evaluate platelet function among ACS patients. Our results show that the mutant allele C was more frequent among ACS ST (+) than ST (-) patients (39% versus 19.8%, resp.), when the wild-type allele was more represented in the ACS ST (-) group (80.2%). The C allele frequency was higher among resistant than nonresistant patients (30% versus 20.8%, resp.). Comparison of ACS patients and healthy controls shows higher frequency of mutant C allele among cases compared to controls (22.73% versus 19.31%, resp.); there was a statistically significant association of the recessive and additive transmission models with the ACS development risk (OR [95% CI] = 1.78 [1.58-5.05], P = 0.01 and OR [95% CI] = 1.23 [0.74-2.03], P < 0.001, resp.), increasing thus the association of this polymorphism with the pathology. Conclusion. Our results suggest that this polymorphism may have a potential effect on Clopidogrel response among our Moroccan ACS patients and also on ACS development.

Catastrophic hemorrhage of adrenal pheochromocytoma following thrombolysis for acute myocardial infarction: case report and literature review.

We describe here the case of a 62-year-old man with acute abdominal syndrome and severe hemorrhagic shock following successful thrombolysis for acute cardiac infarction. Emergency surgical exploration revealed extensive intraperitoneal and retroperitoneal hemorrhage resulting from the rupture of a large adrenal tumor. The diagnosis of pheochromocytoma was confirmed by histological findings. The patient died a few hours after surgery from multiorgan failure despite resuscitation attempts. This report discusses the diagnosis difficulties, treatment approach, and relevant literature.

Nous rapportons l'observation d'un patient âgé de 62 ans, qui présente un syndrome abdominal douloureux aigu associé à un choc hémorragique sévère au décours d'une thrombolyse pour infarctus du myocarde. L'exploration chirurgicale urgente objective une hémorragie extensive retro- et intra péritonéale secondaire à une rupture d'une masse surrénalienne. Le diagnostic de phéochromocytome a été confirmé par l'examen histologique de la pièce opératoire. L'évolution était rapidement fatale, aboutissant au décès du patient par défaillance multi-viscérale quelques heures en postopératoire. Seront discutés à travers cette observation et une revue de la littérature, les difficultés diagnostiques et de prise en charge de cette redoutable complication.