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  1. Hasan SS, Kow CS, Hadi MA, Zaidi STR, Merchant HA
    Am J Cardiovasc Drugs, 2020 Dec;20(6):571-590.
    PMID: 32918209 DOI: 10.1007/s40256-020-00439-5
    INTRODUCTION: The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19).

    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.

  2. Bawadikji AA, Teh CH, Sheikh Abdul Kader MAB, Abdul Wahab MJB, Syed Sulaiman SA, Ibrahim B
    Am J Cardiovasc Drugs, 2020 Apr;20(2):169-177.
    PMID: 31435902 DOI: 10.1007/s40256-019-00364-2
    BACKGROUND: Warfarin is prescribed as an oral anticoagulant to treat/prevent thromboembolism in conditions such as atrial fibrillation. As there is a narrow therapeutic window, treatment with warfarin is challenging. Pharmacometabonomics using nuclear magnetic resonance (NMR) spectroscopy may provide novel techniques for the identification of novel biomarkers of warfarin.

    PURPOSE: The aim was to determine the metabolic fingerprint that predicts warfarin response based on the international normalized ratio (INR) in patients who are already receiving warfarin (phase I: identification) and to ascertain the metabolic fingerprint that discriminates stable from unstable INR in patients starting treatment with warfarin (phase II: validation).

    EXPERIMENTAL APPROACH: A total of 94 blood samples were collected for phase I: 44 patients with stable INR and 50 with unstable INR. Meanwhile, 23 samples were collected for phase II: nine patients with stable INR and 14 with unstable INR. Data analysis was performed using multivariate analysis including principal component analysis and partial least square-discriminate analysis (PLS-DA), followed by univariate and multivariate logistic regression (MVLR) to develop a model to identify unstable INR biomarkers.

    KEY RESULTS: For phase I, the PLS-DA model showed the following results: sensitivity 93.18%, specificity 91.49% and accuracy 92.31%. In the MVLR analysis of phase I, ten regions were associated with unstable INR. For phase II, the PLS-DA model showed the following results: sensitivity 66.67%, specificity 61.54% and accuracy 63.64%.

    CONCLUSIONS AND IMPLICATIONS: We have shown that the pharmacometabonomics technique was able to differentiate between unstable and stable INR with good accuracy. NMR-based pharmacometabonomics has the potential to identify novel biomarkers in plasma, which can be useful in individualizing treatment and controlling warfarin side effects, thus, minimizing undesirable effects in the future.

  3. Ho KT, Chin KW, Ng KS, Alemao E, Rajagopalan S, Yin D
    Am J Cardiovasc Drugs, 2006;6(6):383-91.
    PMID: 17192128
    BACKGROUND: Cardiovascular disease remains a leading cause of death worldwide, with hypercholesterolemia being a major risk factor. Evidence-based consensus guidelines have recommended consideration of increasingly stringent cholesterol-lowering goals, yet most patients do not meet these targets. Coronary heart disease (CHD) event and mortality rates and mean serum cholesterol levels have declined in Singapore in recent years; however, certain groups remain at elevated risk.

    OBJECTIVE: To determine (i) proportions of patients with CHD in Singapore who achieved goals for serum low-density lipoprotein-cholesterol (LDL-C); and (ii) factors influencing goal attainment.

    METHODS: A historical cohort study was conducted using records from the Singapore Cardiac Databank, a national registry of CHD patients. Serum LDL-C goal attainment was assessed in 5174 survivors of acute myocardial infarction or coronary revascularization (i.e. coronary artery bypass graft surgery or percutaneous coronary interventions), of whom 3811 (73.7%) were at very high risk.

    RESULTS: At baseline, the mean patient age was 60.3 years, mean serum value of total cholesterol was 228 mg/dL, and mean LDL-C was 163 mg/dL. Of all CHD patients, approximately 70% did not achieve a serum LDL-C target of <100 mg/dL. Most patients receiving HMG-CoA reductase inhibitor (statin) regimens were treated initially with low- to medium-equipotency regimens and were never titrated to stronger regimens. The vast majority (approximately 94%) of patients at very high risk did not achieve the stringent serum LDL-C target of <70 mg/dL. Patients receiving higher potency statins were significantly more likely to achieve LDL-C goals, whereas those with higher baseline LDL-C levels or Malaysian ethnicity were less likely to achieve LDL-C goals.

    CONCLUSIONS: Most CHD patients in the large group of Singapore residents with CHD in the present study did not achieve recommended LDL-C targets. A more effective disease-management approach, including patient education concerning lifestyle modification (e.g. diet, physical activity), efforts to enhance medication adherence, and more effective, well tolerated therapies such as high-equipotency or high-dose statins and statin combination regimens, may be needed to improve achievement of consensus cholesterol targets. This is the first study of cholesterol goal attainment in a large group of Southeast Asians and serves as a baseline for future evaluations in Asian populations.

  4. Kow CS, Zaidi STR, Hasan SS
    Am J Cardiovasc Drugs, 2020 Jun;20(3):217-221.
    PMID: 32281055 DOI: 10.1007/s40256-020-00406-0
    There is ongoing debate on the safety of renin-angiotensin system (RAS) inhibitors in COVID-19. Recently published studies highlight a potential relationship between cardiovascular disease (CVD) and COVID-19. This article aims to summarize the evidence on the use of RAS inhibitors in CVD patients with COVID-19, focusing on safety issues of the RAS inhibitors and their relationship with COVID-19.
  5. Kow CS, Sunter W, Bain A, Zaidi STR, Hasan SS
    Am J Cardiovasc Drugs, 2020 Aug;20(4):301-309.
    PMID: 32458370 DOI: 10.1007/s40256-020-00415-z
    Many healthcare resources have been and continue to be allocated to the management of patients with COVID-19. Therefore, the ongoing care of patients receiving oral anticoagulation with warfarin is likely to be compromised amid this unprecedented crisis. This article discusses a stepwise algorithm for the management of outpatient warfarin therapy. Alternative management strategies are presented and discussed, including alternative pharmacological therapy options and self-monitoring. Our algorithm aims to help clinicians safely optimize the treatment of patients requiring anticoagulation therapy in the context of the global response to the current pandemic.
  6. Kow CS, Hasan SS
    Am J Cardiovasc Drugs, 2021 Aug 03.
    PMID: 34341972 DOI: 10.1007/s40256-021-00490-w
    PURPOSE: Previously, we have reported potential clinical benefits with the use of statins in patients with coronavirus disease 2019 (COVID-19) in a meta-analysis, where there was a significantly reduced hazard for a fatal or severe course of illness with the use of statins, but the meta-analysis was limited by the small number of studies included, with small heterogeneity among studies, due to the unavailability of more studies at the point of literature search. We aimed to perform an updated systematic review and meta-analysis to summarize the existing evidence on the effect of statins on the clinical outcomes of patients with COVID-19.

    METHODS: Electronic databases, including PubMed, Google Scholar, and Scopus, and preprint servers were searched (last updated June 3, 2021) to identify studies investigating the association between the use of statins in patients with COVID-19 and the development of severe disease and/or mortality. Random-effects model meta-analyses were performed to estimate the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CIs). The outcomes of interest were (1) all-cause mortality and (2) a composite endpoint of severe illness of COVID-19.

    RESULTS: Upon systematic literature search, we identified 35 studies, of which 32 studies reported the outcome of all-cause mortality and 15 studies reported the composite endpoint of severe COVID-19 illness between statin users versus non-statin users with COVID-19. Our meta-analysis revealed that the use of statins was associated with a significantly lower risks of all-cause mortality (HR = 0.70, 95% CI 0.58-0.84, n = 21,127, and OR = 0.63, 95% CI 0.51-0.79, n = 115,097) and the composite endpoint of severe illness (OR = 0.80, 95% CI 0.73-0.88, n = 10,081) in patients with COVID-19, compared to non-use of statins, at the current sample size.

    CONCLUSION: Statin use is associated with a better prognosis in patients with COVID-19. Our findings provide a rationale to investigate the use of statins among patients with COVID-19 in large scale clinical trials.

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