Abdulla Shehab

Familial hypercholesterolaemia: A global call to arms.

Familial Hypercholesterolaemia (FH) is the commonest autosomal co-dominantly inherited condition affecting man. It is caused by mutation in one of three genes, encoding the low-density lipoprotein (LDL) receptor, or the gene for apolipoprotein B (which is the major protein component of the LDL particle), or in the gene coding for PCSK9 (which is involved in the degradation of the LDL-receptor during its cellular recycling). These mutations result in impaired LDL metabolism, leading to life-long elevations in LDL-cholesterol (LDL-C) and development of premature atherosclerotic cardiovascular disease (ASCVD) [1], [2] and [3]. If left untreated, the relative risk of premature coronary artery disease is significantly higher in heterozygous patients than unaffected individuals, with most untreated homozygotes developing ASCVD before the age of 20 and generally not surviving past 30 years [2], [3], [4] and [5]. Although early detection and treatment with statins and other LDL-C lowering therapies can improve survival, FH remains widely underdiagnosed and undertreated [1], thereby representing a major global public health challenge.

Gender Disparities in the Presentation, Management and Outcomes of Acute Coronary Syndrome Patients: Data from the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2)

Background Gender-related differences in mortality of acute coronary syndrome (ACS) have been reported. The extent and causes of these differences in the Middle-East are poorly understood. We studied to what extent difference in outcome, specifically 1-year mortality are attributable to demographic, baseline clinical differences at presentation, and management differences between female and male patients. Methodology/Principal Findings Baseline characteristics, treatment patterns, and 1-year mortality of 7390 ACS patients in 65 hospitals in 6 Arabian Gulf countries were evaluated during 2008–2009, as part of the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). Women were older (61.3±11.8 vs. 55.6±12.4; P<0.001), more overweight (BMI: 28.1±6.6 vs. 26.7±5.1; P<0.001), and more likely to have a history of hypertension, hyperlipidemia or diabetes. Fewer women than men received angiotensin-converting enzyme inhibitors (ACE), aspirin, clopidogrel, beta blockers or statins at discharge. They also underwent fewer invasive procedures including angiography (27.0% vs. 34.0%; P<0.001), percutaneous coronary intervention (PCI) (10.5% vs. 15.6%; P<0.001) and reperfusion therapy (6.9% vs. 20.2%; P<0.001) than men. Women were at higher unadjusted risk for in-hospital death (6.8% vs. 4.0%, P<0.001) and heart failure (HF) (18% vs. 11.8%, P<0.001). Both 1-month and 1-year mortality rates were higher in women than men (11% vs. 7.4% and 17.3% vs. 11.4%, respectively, P<0.001). Both baseline and management differences contributed to a worse outcome in women. Together these variables explained almost all mortality disparities. Conclusions/Significance Differences between genders in mortality appeared to be largely explained by differences in prognostic variables and management patterns. However, the origin of the latter differences need further study.

Prevalence of the Metabolic Syndrome in Patients With Acute Coronary Syndrome in Six Middle Eastern Countries

J Clin Hypertens (Greenwich).

Nonadherence to antihypertensive drugs: A systematic review and meta-analysis.

Background: Hypertension drives the global burden of cardiovascular disease and its prevalence is estimated to increase by 30% by the year 2025. Nonadherence to chronic medication regimens is common; approximately 43% to 65.5% of patients who fail to adhere to prescribed regimens are hypertensive patients. Nonadherence to medications is a potential contributing factor to the occurrence of concomitant diseases. Objective: This systematic review applied a meta-analytic procedure to investigate the medication nonadherence in adult hypertensive patients. Methods: Original research studies, conducted on adult hypertensive patients, using the 8-item Morisky medication adherence scale (MMAS-8) to assess the medication adherence between January 2009 and March 2016 were included. Comprehensive search strategies of 3 databases and MeSH keywords were used to locate eligible literature. Study characteristics, participant demographics, and medication adherence outcomes were recorded. Effect sizes for outcomes were calculated as standardized mean differences using random-effect model to estimate overall mean effects. Results: A total of 28 studies from 15 countries were identified, in total comprising of 13,688 hypertensive patients, were reviewed. Of 25 studies included in the meta-analysis involving 12,603 subjects, a significant number (45.2%) of the hypertensive patients and one-third (31.2%) of the hypertensive patients with comorbidities were nonadherent to medications. However, a higher proportion (83.7%) of medication nonadherence was noticed in uncontrolled blood pressure (BP) patients. Although a higher percentage (54%) of nonadherence to antihypertensive medications was noticed in females (P < 0.001), the risk of nonadherence was 1.3 times higher in males, with a relative risk of 0.883. Overall, nearly two-thirds (62.5%) of the medication nonadherence was noticed in Africans and Asians (43.5%). Conclusion: Nonadherence to antihypertensive medications was noticed in 45% of the subjects studied and a higher proportion of uncontrolled BP (83.7%) was nonadherent to medication. Intervention models aiming to improve adherence should be emphasized.

Suboptimal Control of Lipid Levels: Results from 29 Countries Participating in the Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS)

AIM Five multicentre, cross-sectional Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS) were conducted in 29 countries across Asia, Western Europe, Eastern Europe, the Middle East, and Africa. The surveys assessed the current use and efficacy of lipid-lowering drugs (LLDs) worldwide and identified possible patient and physician characteristics associated with failure to attain low-density lipoprotein cholesterol (LDL-C) goals. The aim of this analysis was to consolidate the global results from these surveys. METHODS The surveys involved patients aged ≥18 years who had been prescribed LLDs for at least 3 months without dose changes for at least 6 weeks. A single visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Cardiovascular risk profile and LDL-C goal attainment were assessed according to the 2004 updated US National Cholesterol Education Program Adult Treatment Panel III guidelines. RESULTS In total, 35 121 patients (mean age: 60.4 years) were included, and 90.3% had been prescribed statin monotherapy. Overall, only 49.4% of patients reached their recommended LDL-C level. LDL-C goals were attained in 54.8% (5084/9273) and 22.8% (3287/14 429) of patients were at high and very high cardiovascular risk, respectively. Factors associated with an increased likelihood of LDL-C goal attainment were lower baseline cardiovascular risk; presence of diabetes mellitus, hypertension, or history of cardiovascular disease; and treatment with simvastatin, atorvastatin, or rosuvastatin (vs. all other LLDs). CONCLUSION LDL-C goal attainment in patients taking LLDs is suboptimal worldwide, particularly in patients at high and very high cardiovascular risk.

Community pharmacy and the extended community pharmacist practice roles: The UAE experiences

Background: The pharmaceutical care and ‘extended’ roles are still not practiced optimally by community pharmacists. Several studies have discussed the practice of community pharmacy in the UAE and have shown that most community pharmacists only counsel patients. However, UAE, has taken initiatives to allow and prepare community pharmacists to practice ‘extended’ roles. Aim of the review: The aim was to review the current roles of community pharmacists in Abu Dhabi Emirate, United Arab Emirates (UAE). Objective: The objective was to encourage community pharmacists toward extending their practice roles. Methods: In 2010, Health Authority Abu Dhabi (HAAD) surveyed community pharmacists, using an online questionnaire, on their preferences toward extending their counseling roles and their opinion of the greatest challenge facing the extension of their counseling roles. Results: Following this survey, several programs have been developed to prepare community pharmacists to undertake these extended counseling roles. In addition to that, HAAD redefined the scope of pharmacist roles to include some extended/enhanced roles. Abu Dhabi Health Services (SEHA) mission is to ensure reliable excellence in healthcare. It has put clear plans to achieve this; these include increasing focus on public health matters, developing and monitoring evidence-based clinical policies, training health professionals to comply with international standards to deliver world-class quality care, among others. Prior to making further plans to extend community pharmacists’ roles, and to ensure the success of these plans, it is imperative to establish the views of community pharmacists in Abu Dhabi on practicing extended roles and to gain understanding and information on what pharmacists see as preferred change strategies or facilitators to change. Conclusions: In an attempt to adapt to the changes occurring and to the growing needs of patients and to maximize the utilization of community pharmacists’ unique structured strategies are needed to be introduced to the community pharmacy profession.

Gender Differences in Acute Coronary Syndrome in Arab Emirati Women—Implications for Clinical Management

Gender differences exist in many aspects of acute coronary syndrome (ACS), including presentation and delay in diagnosis and treatment. The aim of the study was to evaluate gender-related differences in ACS patients in the United Arab Emirates (UAE). We analyzed a subset (n = 1697) of the Gulf Registry of Acute Coronary Events (Gulf RACE) data collected in 2007 of patients with ACS from 18 UAE hospitals. Women were significantly older (mean age: 64.0 ± 12.4 years for females and 50.9 ± 10.6 years for males, P < .001), more often had cardiac risk factors and were significantly less treated with β-blockers and reperfusion therapy. The adjusted mortality rate of women was 4.6% versus 1.2% in men (P < .001). Heart failure was higher in females compared with men (24.6% vs 12.5%; P < .001). Reasons for the high in-hospital mortality in women need to be investigated further.

Impact of Digoxin on Mortality in Patients With Atrial Fibrillation Stratified by Heart Failure: Findings From Gulf Survey of Atrial Fibrillation Events in the Middle East

Objective: The use of digoxin in patients having atrial fibrillation (AF) with or without heart failure (HF) is not without controversy. The aim of this study was to examine the impact of digoxin therapy on mortality stratified by HF. Methods: Gulf Survey of Atrial Fibrillation Events was a prospective, multinational, observational registry of consecutive patients with AF recruited from the emergency department of 23 hospitals in 6 countries in the Middle East. Patients were recruited between October 2009 and June 2010 and followed up for 1 year after enrollment. Analyses were performed using univariate and multivariate statistical techniques. Results: The study included a total of 1962 patients with AF, with an overall mean age of 56 ± 16 years, and 52% (n = 1026) were males. At hospital discharge, digoxin was prescribed in 36% (n = 709) of the patients, whereas HF was present in 27% (n = 528) of the cohort. A total of 225 (12.1%) patients died during the 12-month follow-up period after discharge (5.3% [n = 104] were lost to follow-up). Patients with HF were consistently associated with higher mortality at 1 month (5.1% vs 2.1%; P < .001), 6 months (17.2% vs 5.0%; P < 0.001), and 12 months (24.3% vs 7.6%; P < .001) when compared to those without HF. When stratified by HF, digoxin therapy was associated with significantly higher mortality in those without HF at 6 months (8.7% vs 3.7%; adjusted odds ratio (aOR), 5.07; P < .001) and 12 months (12.3% vs 6.0%; aOR, 4.22; P < .001) but not in those with HF (6 months: 18.6% vs 14.7%; aOR, 1.62; P = .177 and 12 months: 25.4% vs 22.4%; aOR, 1.37; P = .317). Conclusions: In patients with AF and HF, digoxin did not offer any survival advantages. However, in those without HF, digoxin therapy was, in fact, associated with significantly higher long-term mortality.

Alternatives to currently used antimalarial drugs: in search of a magic bullet

Malaria is a major cause of morbidity and mortality in many African countries and parts of Asia and South America. Novel approaches to combating the disease have emerged in recent years and several drug candidates are now being tested clinically. However, it is long before these novel drugs can hit the market, especially due to a scarcity of safety and efficacy data.To reduce the malaria burden, the Medicines for Malaria Venture (MMV) was established in 1999 to develop novel medicines through industry and academic partners’ collaboration. However, no reviews were focused following various preclinical and clinical studies published since the MMV initiation (2000) to till date.We identify promising approaches in the global portfolio of antimalarial medicines, and highlight challenges and patient specific concerns of these novel molecules. We discuss different clinical studies focusing on the evaluation of novel drugs against malaria in different human trials over the past five years.The drugs KAE609 and DDD107498 are still being evaluated in Phase I trials and preclinical developmental studies. Both the safety and efficacy of novel compounds such as KAF156 and DSM265 need to be assessed further, especially for use in pregnant women. Synthetic non-artemisinin ozonides such as OZ277 raised concerns in terms of its insufficient efficacy against high parasitic loads. Aminoquinoline-based scaffolds such as ferroquine are promising but should be combined with good partner drugs for enhanced efficacy. AQ-13 induced electrocardiac events, which led to prolonged QTc intervals. Tafenoquine, the only new anti-relapse scaffold for patients with a glucose-6-phosphate dehydrogenase deficiency, has raised significant concerns due to its hemolytic activity. Other compounds, including methylene blue (potential transmission blocker) and fosmidomycin (DXP reductoisomerase inhibitor), are available but cannot be used in children.At this stage, we are unable to identify a single magic bullet against malaria. Future studies should focus on effective single-dose molecules that can act against all stages of malaria in order to prevent transmission. Newer medicines have also raised concerns in terms of efficacy and safety. Overall, more evidence is needed to effectively reduce the current malaria burden. Treatment strategies that target the blood stage with transmission-blocking properties are needed to prevent future drug resistance.

Design and Rationale of Gulf locals with Acute Coronary Syndrome Events (Gulf Coast) Registry

Objectives: To describe the risk profile, management and one-year outcomes of patients hospitalized with acute coronary syndrome (ACS) in the Gulf region of the Middle East. Subjects and Methods: The Gulf locals with acute coronary syndrome events (Gulf COAST) registry is a prospective, multinational, longitudinal, observational, cohort-based registry of consecutive citizens, from the Gulf region of the Middle East, admitted from January 2012 to January 2013 to 29 hospitals with a diagnosis of ACS. Data entered online included patient demographics, cardiovascular risk profiles, past medical history, physical findings on admission, in-hospital diagnostic tests and therapeutic management, as well as one year outcomes. Results: 3188 patients were recruited. The mean age was 60.4 ± 12.6years (range: 22-112), 2104 (66%) were males and 1084 (34%) females. The discharge diagnosis was ST-segment elevation myocardial infarction (STEMI) in 741 (23.2%), new-onset left bundle branch block myocardial infarction (LBBBMI) in 30 (0.9%), non-ST-segment elevation myocardial infarction (NSTEMI) in 1486 (46.6%) and unstable angina in 931 (29.2%). At hospital presentation, 2105 (66%), 1779 (55.8%), 1703 (53.4%) and 740 (23.2%) had history of hypertension, dyslipidemia, diabetes mellitus and active smoking, respectively. Conclusion: Patients with ACS in our region are young with very high risk profile. The Gulf COAST registry is an example of successful regional collaboration and will provide information on contemporary management of ACS in the region.