METHOD: Literature search was performed within the PubMed, ScienceDirect.com and Google Scholar.
RESULTS: The presence of proline at the C-terminal tripeptide of ACE inhibitor can competitively inhibit the ACE activity. The effects of other amino acids are less studied leading to difficulties in predicting potent peptide sequences. The broad specificity of the enzyme may be due to the dual active sites observed on the somatic ACE. The inhibitors may not necessarily competitively inhibit the enzyme which explains why some reported inhibitors do not have the common ACE inhibitor characteristics. Finally, the in vivo assay has to be carried out before the peptides as the antihypertensive agents can be claimed. The peptides must be absorbed into circulation without being degraded, which will affect their bioavailability and potency. Thus, peptides with strong in vitro IC50 values do not necessarily have the same effect in vivo and vice versa.
CONCLUSION: The relationship between peptide amino acid sequence and inhibitory activity, in vivo studies of the active peptides and bioavailability must be studied before the peptides as antihypertensive agents can be claimed.
METHODS: We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors.
RESULTS: A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB.
DISCUSSION: Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.
OBJECTIVES: To investigate adherence to guideline-based management and mortality of STEMI patients in Malaysia.
DESIGN: Retrospective analysis.
SETTINGS: STEMI patients from 18 participating hospital across Malaysia included in the National Cardiovascular Database-Acute Coronary Syndrome (NCVD-ACS) registry year 2006 to 2013.
PATIENTS AND METHODS: Patients were categorized into four subgroups based on the year of admission (2006 to 2007, 2008 to 2009, 2010 to 2011 and 2012 to 2013). Baseline characteristics and clinical presentation, in-hospital pharmacotherapy, invasive revascularization and in-hospital/30-day mortality were analysed and compared between the subgroups.
MAIN OUTCOME MEASURE(S): Rate of in-hospital catheterization/percutaneous coronary intervention.
RESULTS: The registry contained data on 19483 patients. Intravenous thrombolysis was the main reperfusion therapy. Although the overall rate of in-hospital catheterisation/PCI more than doubled over the study period, while the use of primary PCI only slowly increased from 7.6% in 2006/2007 to 13.6% in 2012/2013. The use of evidence-based oral therapies increased steadily over the years except for ACe-inhibitors and angiotensin-receptor blockers. The adjusted risk ratios (RR) for in-hospital mortality for the four sub-groups have not shown any significant improvement. The 30-day adjusted risk ratios however showed a significant albeit gradual risk reduction (RR 0.773 95% CI 0.679-0.881, P < .001).
CONCLUSION: Adherence to evidence-based treatment in STEMI in Malaysia is still poor especially in terms of the rate of primary PCI. Although there is a general trend toward reduced 30-day mortality, the reduction was only slight over the study period. Drastic effort is needed to improve adherence and clinical outcomes.
LIMITATION: Retrospective registry data with inter-hospital variation.
METHODS: A case-control, cross-sectional population-based nested study (n = 142) included hypertensive subjects treated with ACEI drugs, either lisinopril or enalapril (20 mg, once daily) as monotherapy for 24 weeks. In total seven possible polymorphisms of RAS genes were genotyped. The association between those polymorphisms and the changes in blood pressure were observed in the 24 week treatment.
RESULTS: Statistically significant associations of I, G, T, M and G alleles of ACE (I/D, G2350A), AGT (M235T, T175M and G-6A) respectively were observed in essential hypertensive subjects. The decrease in systolic blood pressure and diastolic blood pressure after 24 weeks of treatment of the patients carrying II, GG, and TT genotypes were greater than the groups carrying DD, AA, MM, MM and GG of I/D, G2350A, M235T, T174M and G-6A genotypes respectively. In contrast, No significant difference was observed between renin gene polymorphisms (Bg/I and MboI) and hypertensives.
CONCLUSIONS: Although this study shows a possible association of polymorphisms of RAS genes with the risk of non-control of HT in ACEI-treated patients and indicates the importance of all this system's components in regulating HT, it needs to be replicated in other data sources.
DESIGN: A retrospective analysis of STEMI patients from 18 hospitals across Malaysia contributing to the Malaysian National Cardiovascular Database-acute coronary syndrome) registry (NCVD-ACS) year 2006-2013.
PARTICIPANTS: 16 517 patients diagnosed of STEMI from 18 hospitals in Malaysia from the year 2006 to 2013.
PRIMARY OUTCOME MEASURES: In-hospital and 30 day post-discharge mortality.
RESULTS: CS complicates 10.6% of all STEMIs in this study. They had unfavourable premorbid conditions and poor outcomes. The in-hospital mortality rate was 34.1% which translates into a 7.14 times mortality risk increment compared with STEMI without CS. Intravenous thrombolysis remained as the main urgent reperfusion modality. Percutaneous coronary interventions (PCI) in CS conferred a 40% risk reduction over non-invasive therapy but were only done in 33.6% of cases. Age over 65, diabetes mellitus, hypertension, chronic lung and kidney disease conferred higher risk of mortality.
CONCLUSION: Mortality rates of CS complicating STEMI in Malaysia are high. In-hospital PCI confers a 40% mortality risk reduction but the rate of PCI among our patients with CS complicating STEMI is still low. Efforts are being made to increase access to invasive therapy for these patients.
MATERIALS AND METHODS: This was a retrospective study conducted at nephrology unit of a tertiary hospital in Kedah. All diabetic ESRD patients who fulfilled the inclusion criteria were identified and recruited for analysis.
RESULTS: The mean duration of DM to ESRD was found to be 14.37 ± 4.42 years. Mean duration for the onset of diabetic nephropathy was 8.73 ± 3.37 years. There was a relative short duration from diabetic nephropathy to ESRD noted, which was 5.63 ± 2.06 years. The mean duration of DM to ESRD for patients receiving RAAS blocker was found to be 18.23 ± 2.38 years as compared to 11.41 ± 2.94 years for those who did not (95% CI: -0.64 to -2.46). For different type of RAAS blockers, namely ACE inhibitor and angiotensin receptor blocker (ARB), there was no significant difference observed pertaining to mean duration of DM to ESRD; 17.89 ± 1.97 years for ACEi and 19.00 ± 4.16 years for ARB (95% CI: -4.74 to 2.52).
DISCUSSION: Time frame from diabetic nephropathy to ESRF among Malaysian population was shorter as compared to findings from other countries with an average period of 15 to 25 years. RAAS blockers should be initiated early in diabetic patients.
OBJECTIVES: To document the prevalence of CHF in the multiracial population of Malaysia, and to describe the clinical features and management of these patients.
SETTING: Busy city centre general hospital in Kuala Lumpur, Malaysia.
RESULTS: Of 1435 acute medical admissions to Kuala Lumpur General Hospital over the 4-week study period, 97 patients (6.7%) were admitted with the primary diagnosis of CHF. Coronary artery disease was the main aetiology of CHF, accounting for almost half (49.5%) the patients, followed by hypertension (18.6%). However, there were variations in associated aetiological factors between ethnic groups, with diabetes mellitus affecting the majority of Indians-as well as underutilisation of standard drugs for CHF, such as the angiotensin converting enzyme (ACE) inhibitors, which were only used in 43.3%.
CONCLUSION: Amongst acute medical admissions to a single centre in Malaysia the prevalence of CHF was 6.7%. Coronary artery disease was the major aetiological factor in heart failure accounting for almost half the admissions. The under-prescription of ACE inhibitors was similar to other clinical surveys carried out amongst Caucasian populations in the West.