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Clinical use of clopidogrel in acute coronary syndrome

Zambahari R, Kwok OH, Javier S, Mak KH, Piyamitr S, Tri Ho HQ, et al.

Int J Clin Pract, 2007 Mar;61(3):473-81.
PMID: 17313616

Several therapeutic approaches have been developed to improve the outcome among patients with acute coronary syndrome (ACS). However, treatment with antithrombotic therapies such as oral glycoprotein IIb/IIIa inhibitors has been limited by the lack of efficacy and excess bleeding complications. As the publication of the landmark study Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), the clinical benefit of early and intermediate-term use of combined antiplatelet agents--clopidogrel plus aspirin--in non-ST-segment elevation myocardial infarction (NSTEMI) patients became evident. Pretreatment and intermediate-term therapy with clopidogrel in NSTEMI ACS patients undergoing percutaneous coronary intervention (PCI) was further supported by the PCI-CURE trial. Recently, the results of two major trials Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28, Clopidogrel and Metoprolol in Myocardial Infarction Trial established the pivotal role of clopidogrel in the other spectrum of ACS-STEMI. Coupled with the results from previous multicentre trials, these two studies provide a guide for the early and long-term use of clopidogrel in the whole spectrum of ACS. A review summarising the results of the recent clinical trials and a discussion on its implications for the clinical management of ACS is presented.
Ethnic differences in acute myocardial infarction in Singapore

Mak KH, Chia KS, Kark JD, Chua T, Tan C, Foong BH, et al.

Eur Heart J, 2003 Jan;24(2):151-60.
PMID: 12573272

AIMS: We compare the myocardial infarction (MI) event and mortality rates among Chinese, Malay and Indian residents of Singapore.
METHODS: Residents, aged 20 to 64 years, with an MI event were identified from hospital discharge listings, postmortem reports, and the Registry of Births and Deaths. All pathology laboratories flagged patients with elevated creatine phosphokinase (CPK) levels. Modified MONICA (multinational monitoring of trends and determinants in cardiovascular disease) criteria were used for determining MI events.
RESULTS: From 1991 to 1999, 12 481 MI events were identified. Chinese patients were older and less likely to have typical symptoms or previous MI. Malays had the highest peak CPK level. Among all three ethnic groups, MI event and age-adjusted case-fatality rates declined. Compared with Chinese, MI event rates were >2-fold and >3-fold higher, and age-standardized coronary mortality rates were 2.4 and 3.0 higher times for Malays and Indians, respectively. Malays have the highest 3.1-year case-fatality, with an adjusted hazard ratio of 1.26 (95% confidence interval, 1.14 to 1.38) compared with Chinese.
CONCLUSION: We found strong ethnic differences in MI event, case-fatality and coronary mortality rates among the three ethnic groups in Singapore. While Indians have the greatest MI event rates, Malays have the highest case-fatality.
Ethnic differences in utilization of invasive cardiac procedures and in long-term survival following acute myocardial infarction

Mak KH, Kark JD, Chia KS, Tan C, Foong BH, Chew SK

Clin Cardiol, 2004 May;27(5):275-80.
PMID: 15188942

BACKGROUND: Ethnic differences in coronary mortality have been documented, and South Asians from the Indian subcontinent are particularly vulnerable.
HYPOTHESIS: This study sought to determine whether there was a difference in the utilization of invasive cardiac procedures and long-term mortality in survivors of myocardial infarction (MI) among Chinese, Malays, and South Asians in Singapore.
METHODS: All MI events in the country were identified and defined by the Singapore Myocardial Infarction Register, which uses modified procedures of the World Health Organization MONICA Project. Information on utilization of coronary angiography, coronary angioplasty, coronary artery bypass graft, and survival was obtained by data linkage with national billing and death registries. Hazard ratios (HR) were calculated using the Cox proportional hazards model with adjustment for baseline characteristics.
RESULTS: From 1991 to 1999, there were 10,294 patients who survived > or = 3 days of MI. Of these, 40.6% underwent coronary angiography and 16.5% a revascularization procedure < or = 28 days. Malays received substantially less angiography (34.0%) and revascularization (11.4%) than Chinese (41.9%, 17.9%) and South Asians (40.0%, 16.3%). The ethnic disparity increased during the 1990s, particularly in the performance of coronary angiography (p = 0.038). While fatality declined during the study period for Chinese and South Asians, the rate remained stable for Malays. After a median follow-up period of 4.1 years, survival was lowest among Malays (adjusted HR, 1.28; 95% confidence interval, 1.15-1.42, compared with Chinese).
CONCLUSION: Ethnic inequalities in invasive cardiac procedures exist in Singapore and were exacerbated in the 1990s. Inequalities in medical care may contribute to the poorer longterm survival among Malays.
Fulltext Ethnic variations in female vulnerability after an acute coronary event

Mak KH, Kark JD, Chia KS, Sim LL, Foong BH, Ding ZP, et al.

Heart, 2004 Jun;90(6):621-6.
PMID: 15145860

OBJECTIVE: To determine the ethnic variation of short and long term female vulnerability after an acute coronary event in a population of Chinese, Indians, and Malays.
DESIGN: Population based registry.
PATIENTS: Residents of Singapore between the ages of 20-64 years with coronary events. Case identification and classification procedures were modified from the MONICA (monitoring trends and determinants in cardiovascular disease) project.
MAIN OUTCOME MEASURES: Adjusted 28 day case fatality and long term mortality.
RESULTS: From 1991 to 1999, there were 16 320 acute coronary events, including 3497 women. Age adjusted 28 day case fatality was greater in women (51.5% v 38.6%, p < 0.001), with a larger sex difference evident among younger Malay patients. This inequality between the sexes was observed in both the pre-hospitalisation and post-admission periods. Among hospitalised patients, women were older, were less likely to have suffered from a previous Q wave or anterior wall myocardial infarction, and had lower peak creatine kinase concentrations. Case fatality was higher among women, with adjusted hazard ratios of 1.64 (95% confidence interval (CI) 1.43 to 1.88) and 1.50 (95% CI 1.37 to 1.64) for 28 day and mean four year follow up periods. There were significant interactions of sex and age with ethnic group (p = 0.017). The adjusted hazards for mortality among Chinese, Indian, and Malay women versus men were 1.30, 1.71, and 1.96, respectively. The excess mortality among women diminished with age.
CONCLUSION: In this multiethnic population, both pre-hospitalisation and post-admission case fatality rates were substantially higher among women. The sex discrepancy in long term mortality was greatest among Malays and in the younger age groups.
Fulltext Extractable impurities from fluoropolymer-based membrane filters - interference in high-throughput, untargeted analysis

Puah PY, Herng Lee DJ, Mak KH, Ang HJ, Chen HC, Moh PY, et al.

RSC Adv, 2019 Oct 07;9(55):31918-31927.
PMID: 35702663 DOI: 10.1039/c9ra06198c

The removal of particles using fluoropolymer-based membrane filters is usually done so to prolong the life span of an analytical column, prevent hardware damage, and reduce signal suppression. Ironically, these membrane filters tend to leach impurities into the samples as the samples are filtered through them. These impurities have the potential to affect the researcher's interpretation in high-throughput, non-targeted analysis. In this study, extractable impurities from different brands of fluoropolymer-based membrane filters present in the filtrate filtered using the said filters were investigated. The results demonstrated that different brand membrane filters and materials tend to elute vastly different numbers of impurities. There were instances whereby the extractable impurities persisted in both the membrane filter and the filtrate despite the filter being pre-conditioned (up to 3 times). Principle component analysis revealed that filtrates at different purge intervals are distant from the unfiltered samples. Pre-conditioning of the PTFE membrane filters could potentially reduce the number of extractable impurities across the tested brands. PVDF filtrates, however, tend to co-cluster with their respective brands, thus suggesting that dissimilarity persists in brands following conditioning. As such, pre-conditioning of the PTFE membrane filters should be encouraged so as to reduce false positive results, while the use of PVDF membrane filters for mass-spectrometry-based untargeted analysis is not advisable as extractable impurities would still persist after 3 rounds of conditioning. Neither the use of different filter brands, nor the use of different filter materials in a sample batch are encouraged as different membrane materials or brands could potentially elute varying impurities.