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  1. Mazlan-Kepli W, Dawson J, Berry C, Walters M
    Heart, 2019 01;105(1):67-74.
    PMID: 30030335 DOI: 10.1136/heartjnl-2018-313148
    OBJECTIVE: To assess whether cardiovascular events are increased after cessation of dual antiplatelet therapy (DAPT) following acute coronary syndrome (ACS) and to explore predictors for recurrent events after DAPT cessation during long-term follow-up.

    METHODS: We did a retrospective observational cohort study. We included consecutive people with ACS who were discharged from Scottish hospitals between January 2008 and December 2013 and who received DAPT after discharge followed by antiplatelet monotherapy. The rates of cardiovascular events were assessed during each 90-day period of DAPT treatment and 90-day period after stopping DAPT. Cardiovascular events were defined as a composite of death, ACS, transient ischaemic attack or stroke. Cox regression was used to identify predictors of cardiovascular events following DAPT cessation.

    RESULTS: 1340 patients were included (62% male, mean age 64.9 (13.0) years). Cardiovascular events occurred in 15.7% (n=211) during the DAPT period (mean DAPT duration 175.1 (155.3) days) and in 16.7% (n=188) following DAPT cessation (mean of 2.7 years follow-up). Independent predictors for a cardiovascular event following DAPT cessation were age (HR 1.07; 95% CI 1.05 to 1.08; p<0.001), DAPT duration (HR 0.997; 95% CI 0.995 to 0.998; p<0.001) and having revascularisation therapy during the index admission (HR 0.58; 95% CI 0.39 to 0.85; p=0.005).

    CONCLUSIONS: The rate of cardiovascular events was not significantly increased in the early period post-DAPT cessation compared with later periods in this ACS population. Increasing age, DAPT duration and lack of revascularisation therapy were associated with increased risk of cardiovascular events during long-term follow-up after DAPT cessation.

  2. Kubas MA, Shabaruddin FH, Mazlan-Kepli W, Jagan N, Mohamed S, Mohamed Nazar NI, et al.
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S781-S786.
    PMID: 33828378 DOI: 10.4103/jpbs.JPBS_381_19
    Introduction: Non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran and rivaroxaban, are now available for stroke prevention in patients with atrial fibrillation (AF) and are often clinically preferred over vitamin K antagonists (VKAs), such as warfarin. Data describing adherence and persistence to NOACs in real-life clinical practice in Malaysia are scarce. This study aimed to assess adherence and persistence to NOACs in patients with AF in two tertiary-care referral centers: Hospital Kuala Lumpur (HKL) and Hospital Serdang (HSDG).

    Materials and Methods: This was a retrospective cohort study that included all patients with AF who were treated with NOACs (dabigatran or rivaroxaban) in HKL and HSDG. Data were obtained from medical records and pharmacy databases. Adherence was assessed using proportion of days covered (PDC) over a 1-year duration. High adherence was defined as PDC ≥80%. A gap of >60 days between two consecutive refills was used to define non-persistence.

    Result: There were 281 patients who met the inclusion criteria, with 54.1% (n = 152) male. There were 75.1% (n = 211) patients on dabigatran and others on rivaroxaban. Only 66.9% (n = 188) of patients achieved high adherence with PDC ≥80% and 69.8% (n = 196) were persistence with >60-day gap over 12 months. Adherence and persistence were both influenced by treatment center, whereas polypharmacy only influenced adherence.

    Conclusion: Overall adherence and persistence to NOACs were suboptimal and varied between treatment centers, potentially due to institution-specific administrative and clinical practice differences. Clinical care and outcomes can potentially be optimized by identifying factors affecting adherence and persistence and by implementing interventions to improving them.

  3. Mazlan-Kepli W, Macisaac RL, Walters M, Bath PMW, Dawson J, VISTA Collaborators
    Br J Clin Pharmacol, 2017 Sep;83(9):2045-2055.
    PMID: 28299795 DOI: 10.1111/bcp.13290
    AIMS: Antiplatelet drugs are often discontinued early after ischaemic stroke, either because of poor compliance, complications or withdrawal of care. It is unclear whether this places patients at increased risk of recurrence. We explored the association between cardiovascular event rate and persistence with prescribed antiplatelet drugs.

    METHODS: We used a matched case-control design using the Virtual International Stroke Trials Archive (VISTA). Cases were patients who had an acute coronary syndrome, recurrent stroke or transient ischaemic attack within 90 days post-stroke and were matched for age ± 10 years and sex with up to four controls. Antiplatelet use was categorized as persistent (used for >3 days and continued up to day 90), early cessation (used antiplatelet <3 days) or stopped/interrupted users (used for >3 days but stopped prior to day 90). These categories were compared in cases and controls using a conditional logistic regression model that adjusted for potential confounders.

    RESULTS: A total of 970 patients were included, of whom 194 were cases and 776 were matched controls. At 90 days, 10 cases (5.2%) and 58 controls (7.5%) stopped/interrupted their antiplatelet. The risk of cardiovascular event was not different in stopped/interrupted users (adjusted odds ratio 0.70, 95% confidence interval 0.33, 1.48; P = 0.352) and early cessations (adjusted odds ratio 1.04, 95% confidence interval 0.62, 1.74; P = 0.876) when compared to persistent users.

    CONCLUSION: We found no increased risk in patients who stopped and interrupted antiplatelets early after stroke but the study was limited by a small sample size and further research is needed.

  4. Lee SL, Ong TJ, Mazlan-Kepli W, Mageswaran A, Tan KH, Abd-Malek AM, et al.
    World J Cardiol, 2021 Sep 26;13(9):483-492.
    PMID: 34621493 DOI: 10.4330/wjc.v13.i9.483
    BACKGROUND: The quality of warfarin therapy can be determined by the time in the therapeutic range (TTR) of international normalized ratio (INR). The estimated minimum TTR needed to achieve a benefit from warfarin therapy is ≥ 60%.

    AIM: To determine TTR and the predictors of poor TTR among atrial fibrillation patients who receive warfarin therapy.

    METHODS: A retrospective observational study was conducted at a cardiology referral center in Selangor, Malaysia. A total of 420 patients with atrial fibrillation and under follow-up at the pharmacist led Warfarin Medication Therapeutic Adherence Clinic between January 2014 and December 2018 were included. Patients' clinical data, information related to warfarin therapy, and INR readings were traced through electronic Hospital Information system. A data collection form was used for data collection. The percentage of days when INR was within range was calculated using the Rosendaal method. The poor INR control category was defined as a TTR < 60%. Predictors for poor TTR were further determined by using logistic regression.

    RESULTS: A total of 420 patients [54.0% male; mean age 65.7 (10.9) years] were included. The calculated mean and median TTR were 60.6% ± 20.6% and 64% (interquartile range 48%-75%), respectively. Of the included patients, 57.6% (n = 242) were in the good control category and 42.4% (n = 178) were in the poor control category. The annual calculated mean TTR between the year 2014 and 2018 ranged from 59.7% and 67.3%. A high HAS-BLED score of ≥ 3 was associated with poor TTR (adjusted odds ratio, 2.525; 95% confidence interval: 1.6-3.9, P < 0.001).

    CONCLUSION: In our population, a high HAS-BLED score was associated with poor TTR. This could provide an important insight when initiating an oral anticoagulant for these patients. Patients with a high HAS-BLED score may obtain less benefit from warfarin therapy and should be considered for other available oral anticoagulants for maximum benefit.

  5. Koh HP, Jagan N, George D, Mazlan-Kepli W, Mohamed S, Lim HT, et al.
    J Thromb Thrombolysis, 2021 Oct;52(3):836-847.
    PMID: 33748900 DOI: 10.1007/s11239-021-02426-2
    There is a wide variation on the efficacy of three-factor Prothrombin Complex Concentrate (3F-PCC) in warfarin reversal. We aimed to determine the efficacy and safety of 3F-PCC in warfarin reversal. This multicentre prospective study analysed data from adult patients on warfarin who received 3F-PCC (Prothrombinex-VF®) for anticoagulation reversal between June 2019 to October 2020. Purposive sampling was used in this study. Study endpoints included target INR achievement, adverse drug reactions (ADRs), and in-hospital all-cause mortality. Logistic regression analyses were used to assess independent predictors of study endpoints. One-hundred thirty-seven patients with a median age of 68 (59-76) years were recruited, who were predominantly male (59.9%, n = 82). A total of 102 patients required 3F-PCC for life-threatening (40.9%, n = 56) and clinically significant bleeding (33.6%, n = 46). Initial INRs ranged from 1.55 to undetectable high (> 26). All patients had INR reduction, of which 62% (n = 85) achieved target INR, whereas 12.4% (n = 17) achieved INR below the target range. Median INR was reduced from 4.76 (3.14-8.32) to 1.54 (1.27-1.88) post-3F-PCC (p 
  6. Hoo YY, Mazlan-Kepli W, Hasan WNHW, Chen FJ, Devadas P, Chow YY, et al.
    J Saudi Heart Assoc, 2021;33(2):149-156.
    PMID: 34183912 DOI: 10.37616/2212-5043.1247
    Objectives: Heart failure [HF] hospital readmissions are a continued challenge in the care of HF patients, which contribute substantially to the high costs of the disease and high mortality rate in lower to middle income country. We implemented a quality improvement project to improve patient outcomes and resource utilization.

    Methods: This study was a prospective cohort design with a historical comparison group. It was conducted to assess the difference in 30-day readmissions and mortality and to assess compliance rate with HF guideline between the historical pre-intervention audit 1 cohort and prospective post-intervention audit 2 cohorts. Audit 1 cohort were recruited from January to February 2019, whereas, audit 2 cohort which received the bundled intervention program were recruited from July to December 2019. Clinical outcomes were compared between cohorts using 30-day readmissions and mortality.

    Results: A total of 50 and 164 patients were included in audit 1 and audit 2 cohort, respectively. Patients in the audit 2 cohort were younger [63.0 ± 14.5 in audit 1 vs 56.5 ± 12.7 in audit 2, p = 0.003] and majority were male [50.0% in audit 1 vs 72.0% in audit2, p = 0.004]. Thirty-day readmissions were significantly different [36.0% audit 1 vs. 22.0% audit 2, p = 0.045], but the mortality rates were similar [4.0%% audit 1 vs. 5.5% audit 2, p = 0.677] between two cohorts.

    Conclusion: A significant decrease in 30-day readmissions was observed in the post-intervention audit 2 cohort in our setting. Further study in larger population and prolong study follow-up is warranted.

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