Definite stent thrombosis among Malaysian population: predictors and insights of mechanisms from intracoronary imaging

@#Introduction: Stent thrombosis (ST) is an uncommon, but significant complication following angioplasty. We aimed to examine the predictors, clinical outcomes and mechanism of definite ST cases among patients who underwent percutaneous coronary intervention (PCI). Methods: This was a retrospective observational registry of 14,935 patients from the year 2011 till 2015. Clinical characteristics, clinical outcome and intracoronary imaging data were recorded in all the patients. The SPSS Statistic version 24 was used for statistical analysis. The Cox regression hazard model was used to report calculate the hazard ratio (HR) with a 95% confidence interval (95%CI). Independent predictors of ST were identified by univariate logistic regression analysis. Variables that showed a statistically significant effect in univariate analyses were entered in a multivariate Cox proportional hazards model. A p-value<0.05 was regarded as significant. Results: The incidence of definite ST was 0.25% (37 out of 14935 patients). 75% of ST group patients presented with ST elevation myocardial infarction (75% vs. 19.8%, p<0.01). There was higher mortality among patients with ST when compared to the group without ST (Hazard Ratio, HR=10.69, 95%CI: 1.13, 100). Two independent predictors of ST were 1) previous history of acute myocardial infarction (HR=2.36, 95%CI: 1.19, 4.70) and 2) PCI in the context of acute coronary syndrome when compared to elective PCI (HR=37, 95%CI: 15.7, 91.5). Examination of 19 ST cases with intracoronary imaging identified nine cases (47%) of underexpanded stents and five cases (26%) of malopposition of stents. Conclusions: ST is associated with high mortality. PCI in acute coronary syndrome setting and a previous history of acute myocardial infarction were significant predictors for ST. Intracoronary imaging identified stent underexpansion and malopposition as common reasons for ST. In cases where the risk of ST is high, the use of intracoronary imaging guided PCI is recommended.

Assessment of Predicted Rate and Associated Factors of Dabigatran-induced Bleeding Events in Malaysian Patients with Non-Valvular Atrial Fibrillation.

PURPOSE: To assess the predicted rate and the factors associated with bleeding events among patients with non-valvular atrial fibrillation (NVAF) receiving dabigatran therapy. METHODS: This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified using pharmacy supply database or novel oral anticoagulant (NOAC) registry. Demographics, clinical data and laboratory test results were extracted from the medical records of the patients or electronic databases. The main outcome measure is the occurrence of a bleeding event. Bleeding events were classified into major bleeding, clinically relevant non-major bleeding, or minor bleeding, according to the International Society on Thrombosis and Haemostasis criteria. We consider clinically relevant non-major bleeding events or major bleeding events as clinically relevant bleeding events. An occurrence of any bleeding event was recorded from the initiation of NOAC therapy until the death of a patient, or the date of permanent discontinuation of NOAC use, or the last day of data collection. The predicted rate of dabigatran-induced bleeding events per 100 patient-years was estimated. RESULTS: During a median follow-up period of 18 months, 73 patients experienced 90 bleeding events. Among these patients, 25 including 4 fatal cases, experienced major bleeding events. The predicted rate per 100 patient-years of follow-up of any bleeding events was 9.0 [95% CI 6.9 to 11.1]; clinically relevant bleeding events 6.0 [95% CI 4.8 to 8.3], and major bleeding events 3.0 [95% CI 1.9 to 4.2]. The independent risk factor for clinically relevant bleeding events is prior bleeding. While prior bleeding or congestive heart failure is linked with major bleeding events. CONCLUSIONS: The predicted rate for dabigatran-induced major bleeding episodes is low but these adverse events carry a high fatality risk. Preventive measures should target older patients who have prior bleeding or congestive heart failure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

A comparison of dabigatran and warfarin for stroke prevention in elderly Asian population with nonvalvular atrial fibrillation: An audit of current practice in Malaysia

Introduction: Atrial fibrillation (AF) is the most commoncardiac arrhythmia with significant morbidity and mortalityin relation to thromboembolic stroke. Our study aimed toevaluate the safety and efficacy of dabigatran in strokeprevention in elderly patient with nonvalvular AF with regardto the risk of ischemic stroke and intracranial haemorrhage(ICH) in real-world setting.Methods: A retrospective cohort study of 200 patients ondabigatran and warfarin from January 2009 till September2016 was carried out. Data were collected for 100 patients ondabigatran and 100 patients on warfarin.Results: The mean follow-up period was 340.7±322.3 daysfor dabigatran group and 410.5±321.2 days for warfaringroup. The mean time in therapeutic range (TTR) was52±18.7%. The mean CHA2DS2 -VASc score for dabigatrangroup was 4.4±1.1 while 5.0±1.5 for warfarin group. None indabigatran group experienced ischemic stroke compared toone patient in warfarin group (p=0.316). There was onepatient in dabigatran group suffered from ICH compared tonone in warfarin group (p=0.316). Four patients in warfaringroup experienced minor bleeding, while none fromdabigatran group (p=0.043).Conclusion: Overall bleeding events were significantly lowerin dabigatran group compared to warfarin group. In thepresence of suboptimal TTR rates and inconveniences withwarfarin therapy, non-vitamin-K antagonist oralanticoagulants (NOAC) are the preferred agents for strokeprevention in elderly Asian patients for nonvalvula

A Comparison of Dabigatran With Warfarin for Stroke Prevention in Atrial Fibrillation in an Asian Population.

BACKGROUND: The Asian population with atrial fibrillation (AF) have a higher risk of stroke than the caucasian population and a higher risk of intracranial bleeding when anticoagulated with warfarin. There are few real-world studies comparing the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among Asian patients to assess its outcomes of ischemic stroke and hemorrhagic stroke. METHODS: A retrospective cohort study of 1000 patients on dabigatran and warfarin from 2009 to 2013. RESULTS: Data were available for 500 patients on dabigatran and 500 patients on warfarin. The average follow-up duration was 315 ± 280 days in the dabigatran group and 355 ± 232 in the warfarin group. The time in therapeutic range (TTR) was 53.2% in the warfarin-treated group, with 32.8% of patients in the subtherapeutic international normalized ratio range of <2. None of the patients in the dabigatran group had ischemic cerebrovascular accident (CVA) compared to 4 (0.8%) patients in the warfarin group, hazard ratio (HR) 0.13, P = .3. There was 1 (0.2%) patient in both dabigatran and warfarin groups with hemorrhagic CVA (HR 1.16, P = .92). There were 3 (0.6%) patients with major bleeding in the dabigatran group compared to 2 (0.4%) patients in the warfarin group (HR 1.57, P = .59). CONCLUSION: There were similar rates of efficacy for outcomes of ischemic CVA, hemorrhagic CVA, and bleeding when comparing dabigatran with warfarin. Our study shows that despite similar efficacy, suboptimal TTR rates and inconveniences with warfarin demonstrate that NOACs are preferred for stroke prevention in AF.

A single centre experience of the efficacy and safety of dabigatran etexilate used for stroke prevention in atrial fibrillation.

The use of novel anticoagulants such as dabigatran are increasing. Despite increased risks of intracerebral haemorrhage with warfarin among Asians, there is little published data on dabigatran to assess 'real world' efficacy and safety of dabigatran therapy in Asia. This was a retrospective observational study of patients prescribed dabigatran between 2010 and 2013. Data was available for 510 patients: median age 68 years (range 20-91), median CHA2DS2-VASc score was 2 and median HAS-BLED score was 2. The average follow-up duration of 315 days (range: 1-1,096). The overall discontinuation rate was 16% after a median 252 days of treatment with dabigatran. There were 17 (3.3%) patients with minor bleeding, 2 (0.4%) had major bleeding episodes. 20 patients (3.9%) developed dyspepsia which was the most common side effect. The rate of occurrences of adverse effects and bleeding were lower than those seen in the RE-LY trial. None of the patients had an ischaemic stroke, 1 (0.2%) patient had a haemorrhagic stroke. Out of 510 patients, 158 patients (31%) were switched to dabigatran from warfarin. This showed that patients frequently preferred the dabigatran due to convenience when given a choice to switch from warfarin. We report one of the largest registry of Asian patients. Reassuringly, we found that our cohort had a low rate of rate of ischaemic stroke, low rates of side effects and bleeding with the drug.

B-type natriuretic Peptide and the right heart.

B-type natriuretic Peptide (BNP) is elevated in conditions with ventricular volume and pressure overload. The physiological, diagnostic and therapeutic role of BNP in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH) are reviewed in this article. BNP levels can be used to differentiate between breathless patients with a respiratory disease and those with PAH. BNP has been shown to correlate with mean pulmonary arterial pressure and pulmonary vascular resistance in patients with PAH, whether primary or secondary. BNP is also a predictor of mortality in patients with primary pulmonary hypertension. These are important clinical implications in that a non-invasive blood test may be used to identify patients who require more invasive procedures (such as cardiac catheterization). There is increasing evidence that BNP or NT-proBNP measurements may also be used to guide therapy (e.g. pulmonary vasorelaxants) in PAH. Enhancement of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH and hence, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.

Natriuretic peptides, respiratory disease, and the right heart.

It is well-recognized that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are raised in conditions with ventricular volume and pressure overload. In addition to this established role in left ventricular congestive cardiac failure, there is good evidence that BNP has a diagnostic role in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH). For example, BNP levels can be used to differentiate between dyspneic patients with pure respiratory defects and those with RV dysfunction. Studies in patients with PAH have demonstrated significant correlations between BNP levels and mean pulmonary arterial pressure as well as pulmonary vascular resistance. Additionally, BNP has a prognostic role in patients with RV pressure overload and pulmonary hypertension, and it offers a noninvasive test that can be used to guide therapy in patients with PAH. However, although measured plasma proBNP levels are raised in conditions with RV overload, its biological significance is still not well-understood. In this article, we review the general physiologic and potential therapeutic role of natriuretic peptides in respiratory disease, RV dysfunction, and PAH. Furthermore, we assess the various clues toward natriuretic peptide action coming from laboratory studies. ANP and BNP knockout mice develop cardiac fibrosis and hypertrophy. Potentiation of the natriuretic pathway has been shown to reduce cardiac hypertrophy and PAH. This is likely to take place as a result of increased intracellular cyclic guanosine monophosphate levels and subsequent pulmonary vasorelaxant activity. In view of this evidence, there may be a rationale for the therapeutic use of recombinant BNP or neutral endopeptidase inhibitors under conditions of RV dysfunction and PAH.