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Background ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. Methods This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. Results STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). Conclusion A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.

Background To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y12 receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD. Methods This prospective (April 2013–December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI. Discussion The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI. Trial registration Trial registration name is “Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy” (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.

Background: Hajj is the largest human gathering with over 2 million people. We evaluated the effect of bundle care intervention on mortality. Methods: A population-based, before and after study compared the effect of an intervention on mortality. The intervention included recruitment of cardiac team, introducing 24/7 catheterization service, cardiac coordination, standardized cardiac care pathways, and establishment of an effective transportation system. Results: Cardiac mortality accounted for about 52% of all in-hospital deaths before intervention in 2009. This decreased significantly to 43.3%, 32.5%, and 19.7% in 2009, 2010, and 2011, respectively. In-hospital mortality of acute coronary syndromes was 4.7%, 4.6%, and 3.0%, in the years 2009, 2010, and 2011, respectively. Mortality due to other causes remained largely unaffected. There was no significant change in the national mortality due to cardiac causes over the same period provided a reassurance that the observed improvement in in-hospital acute coronary syndrome mortality was not due to overall improvement in health care. The numbers of cardiac catheterization procedures increased 3-fold and cardiac surgical procedures increased 5-fold between 2009 and 2011. Conclusions: In this study, we found that an evidence-based intensive bundle care intervention substantially reduced the cardiac mortality among the pilgrims assembling for Hajj in Makkah.

Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h(2) = 0.53, S.E. = 0.1, p = 4e(-12)) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations.

Background Religious pilgrimage, or Hajj, is a basic tenet of the Islamic doctrine. Each year approximately 3 million pilgrims congregate for up to 2 weeks in a Aim To assess the impact of SCHIP on cardiac mortality during Hajj. Methods A team of Cardiologists, specialists, nurses with access to three cardiac catherization laboratories provided 24-h-a-day support to 13 local hospitals throughout the Hajj period. Cardiac and all causes mortality adjusting for the potential other covariates were statistically analyzed using time series data before and after intervention. Results Cardiac death rates during 2006, 2007 and 2008 were 51.7%, 50.6% and 53.2%. After SCHIP introduction rates in 2009, 2010 and 2011 were 27%, 32.5% and 21.5%. The in-hospital mortality for ACS were 4.7%, 4.6% and 3.0%. The number of cardiac procedure performed in 2 weeks during Hajj 2009, 2010, and 2011 were 183, 288 and 550. The majority of the procedure in the last 3 years were coronary catherization 90.1%, 80.9% and 86.7% . The rates of open heart surgery were 7%, 5.2% and 4.5% . Conclusion After introduction of SCHIP, cardiac and in-hospital mortality substantially reduced. Future introduction of mobile cardiac catherization laboratories may further reduce cardiac mortality.

Introduction: Single nucleotide polymorphisms (SNPs) of the β2 -adrenergic receptor (β2 -AR) gene have been implicated in the pathogenesis of cardiovascular diseases. This study evaluated two β2 -AR SNPs in association with myocardial infarction (MI), namely arginine-glycine (G16R) substitution at codon 16 and glutamine-glutamic (Q27E) substitution at condon 27. Objectives: Therefore, our main objective was to determine the association of these two SNPs among patients with MI with and without type 2 diabetes (T2D). Materials and Methods: Blood samples were collected from 201 MI patients with and without diabetes and from 115 controls and the β2 -AR gene polymorphisms at codon 16 and codon 27 were assessed by restriction fragment length polymorphism. The χ2 test was used to compare differences between groups. Results: The SNPs did not deviate significantly from Hardy-Weinberg equilibrium in the control population. The allele and genotype frequencies of the β2 -AR gene polymorphism at codon 16 (G16R) was significantly different between MI cases and controls (χ2 = 10.495, P < 0.05 and χ2 = 8.849, P < 0.05, respectively). No significant difference in genotype and allele frequencies at codon 27 was shown between these two groups (χ2 = 2.661, P ≥ 0.05 and χ2 = 1.587, P ≥ 0.05, respectively). When the MI patients with and without T2D were pooled together, genotype distribution was different between cases and controls at codon 16 (χ2 = 4.631, P = 0.099) and codon 27 (χ2 = 7.247, P = 0.027). However, no significant differences were found in allele frequencies for codon 16 and codon 27 between the two groups (χ2 = 0.628, P = 0.428; χ2 = 0.33, P = 0.565, respectively). Conclusion: Our findings indicate a moderate association of the β2 -AR G16R gene polymorphism with MI suggesting that this gene plays a universal role in the development of MI across ethnicities. However, there was no association of β2 -AR G16R gene polymorphism with diabetic patients with MI.