Antihypertensive treatments and risks of lung Cancer: a large population-based cohort study in Hong Kong.

BACKGROUND: There is a growing concern that the use of anti-hypertensives may be associated with an increased risk of cancer, but it remains uncertain for the association between anti-hypertensives and lung cancer risk, as well as their interaction with aspirin in chemoprotective effects. METHODS: The goal of this study is to assess the association between anti-hypertensives use and the risk of lung cancer, as well as the chemopreventive impacts from the combination usage of aspirin and anti-hypertensives. A retrospective cohort study was conducted based on all the public hospital electronic medical records in Hong Kong. Patients with prescription records of anti-hypertensives (ACEi/ARB, CCB, ß-blocker,α-blocker) and/or aspirin were included as the exposure groups. Using the Cox proportional hazards model with inverse probability weighting, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for lung cancer risk from anti-hypertensives usage or combination usage of aspirin with anti-hypertensives. The likelihood ratio test and interaction model were adopted for exploring the interaction effects with aspirin. RESULTS: A total of 6592 and 84,116 lung cancer cases were identified from the groups of anti-hypertensives users and anti-hypertensives users with aspirin, respectively. The group of non-aspirin patients who received anti-hypertensives showed a significantly lower risk of lung cancer (HR: 0.63, 95% CI: 0.60-0.66), compared to those without anti-hypertensives. When aspirin and α-blocker were used simultaneously, it could lower the risk of lung cancer significantly (HR: 0.53, 95% CI: 0.34-0.84). Moreover, the lower risk of lung cancer persisted with a longer follow-up period of anti-hypertensives usage. Combination usage with aspirin in the users of ACEi/ARB, CCB, and α-blocker showed significant interaction effects. However, the smoking effect could not be eliminated in this analysis. DISCUSSION: Anti-hypertensive treatment was associated with a lower risk of lung cancer, which is associated with the anti-hypertensives exposure period. The potential interaction on the chemopreventive influence from combination usage of α-blocker and aspirin might exist. More corroborations on these findings are needed to focus on the different settings in future studies.

Efficacy and safety comparing prasugrel/ticagrelor and clopidogrel in Hong Kong post-acute coronary syndrome patients-A 10-year cohort study.

BACKGROUND: Clinical evidence of prasugrel/ticagrelor in dual antiplatelet therapy (DAPT) in Asian acute coronary syndrome (ACS) population remains inconclusive. We aimed to compare the clinical efficacy and safety of prasugrel/ticagrelor compared to clopidogrel as part of DAPT in Hong Kong ACS population for 10 years. HYPOTHESIS: Prasugrel/ticagrelor, compared to clopidogrel, reduces risk of major adverse cardiovascular event (MACE) in Hong Kong ACS population. METHODS: The retrospective observational cohort study included patients admitted to seven institutions under Hospital Authority Hong Kong with diagnosis of ACS during 2008-2017. Risk of MACE, defined as composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke, and risk of any bleeding leading to hospitalization were examined. Baseline characteristics difference was adjusted by propensity score (PS) matching. Adjusted Cox regression model was used to estimate hazard ratio of interested outcome. RESULTS: In PS matched cohort including 944 patients in each group, MACE risk reduction of 40% from 1 year to 5 years after index ACS event was observed in prasugrel/ticagrelor group (HR 0.60, 95% CI 0.39-0.91, p = .015). The risk reduction was highly driven by MI reduction (HR 0.54, 95% CI 0.33-0.91, p = .019). Lower bleeding risk was observed in prasugrel/ticagrelor group compared to clopidogrel from 1 year to 5 years (HR 0.46, 95% CI 0.21-1.00, p = .051). CONCLUSIONS: Prasugrel/ticagrelor showed MACE risk reduction over clopidogrel as part of DAPT up to 5 years after index event, while prasugrel/ticagrelor was not associated with increased bleeding risk.

Warfarin control in Hong Kong clinical practice: a single-centre observational study.

INTRODUCTION: Time in therapeutic range (TTR) assesses the safety and effectiveness of warfarin therapy using the international normalised ratio. This study investigated the TTR in Hong Kong patients using both European and Japanese therapeutic ranges and patients' economic and clinical outcomes. Predictors of poor warfarin control and patient knowledge concerning warfarin therapy were assessed. METHODS: A 5-month observational study with retrospective and prospective components was conducted in the Prince of Wales Hospital. The study examined electronic patient records of patients who received warfarin for at least 1 year during the period from January 2010 to August 2015. Patient knowledge was assessed via phone interview using the Oral Anticoagulation Knowledge (OAK) test. RESULTS: In total, 259 patients were included; 174 completed the OAK test. The calculated mean TTR was 40.2±17.1% (European therapeutic range), compared with 49.1±16.1% (Japanese therapeutic range) [P<0.001]. Mean TTR was higher in patients with atrial fibrillation than in patients with prosthetic heart valve (P<0.001). The abilities of TTR to predict clinical and economic outcomes were comparable between European and Japanese therapeutic ranges. Patients with ideal TTR had fewer clinical complications and lower healthcare costs. Patients with younger age exhibited worse TTR, as did those with concurrent use of furosemide, famotidine, or simvastatin. Mean OAK test score was 54.1%. Only 24 (13.8%) patients achieved a satisfactory overall score of ≥75% in the test. CONCLUSION: Warfarin use in Hong Kong patients was poorly controlled, regardless of indication. Patient knowledge concerning warfarin use was suboptimal; thus, additional patient education is warranted regarding warfarin.

A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors.

Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted.