ResearchPad - antiplatelet-therapy https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The precise long-term outcomes of adult IgA nephropathy by mail questionnaires: Better renal survival compared to earlier cohort studies]]> https://www.researchpad.co/article/elastic_article_14721 The estimated 20-year renal survival rate of immunoglobulin A (IgA) nephropathy is approx. 60%, but it is difficult to determine the 'big picture' for IgA nephropathy because a biopsy is essential for its diagnosis. Here we attempted to determine the longer and more precise renal prognosis of IgA nephropathy. We examined 310 patients with primary IgA nephropathy. Using the patients' clinical records and histological reports from our hospital and other clinics, we surveyed their renal prognoses and treatments within 1 year post-biopsy, and we sent questionnaires to the patients who had stopped visiting any hospital. We set renal death as the primary endpoint and analyzed factors related to renal death. The total patient cohort was 267: 159 males, 108 females; average age at biopsy, 37.7 years; average estimated glomerular filtration rate (eGFR), 69.7 mL/min/1.73m2; urinary protein, 1.3 g/day. The mean follow-up duration was prolonged to 13.8±8.9 years (vs. 9.2±8.5 years using only medical records). The 10- and 20-year follow-up rates were 61.7% and 27.3%. The 10-, 20-year renal survival rates were 83.6% and 72.5%. Lower eGFR, hypertension, and smoking were revealed as factors independently related to renal death. To study survival of relatively benign diseases such as IgA nephropathy, longer survival rate was affected by many censoring cases. The results regarding the long-term renal prognoses of IgA nephropathy patients (including those with a mild phenotype) obtained by our analysis of a questionnaire sent to the patients provided more precise and longer-term prognoses compared to earlier studies.

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<![CDATA[Rivaroxaban administration after acute ischemic stroke: The RELAXED study]]> https://www.researchpad.co/article/5c6dca1cd5eed0c48452a7cf

The efficacy of early anticoagulation in acute stroke with nonvalvular atrial fibrillation (NVAF) remains unclear. We performed a study to evaluate the risk of recurrent ischemic stroke (IS) and major bleeding in acute IS patients with NVAF who started rivaroxaban. This observational study evaluated patients with NVAF and acute IS/transient ischemic attack (TIA) in the middle cerebral arterial territory who started rivaroxaban within 30 days after the index IS/TIA. The primary endpoints were recurrent IS and major bleeding within 90 days after the index IS/TIA. The relationship between the endpoints and the time to start rivaroxaban was evaluated by correlation analysis using cerebral infarct volume, determined by diffusion-weighted magnetic resonance images within 48 hours of onset of the index IS/TIA. Of 1309 patients analyzed, recurrent IS occurred in 30 (2.3%) and major bleeding in 11 (0.8%) patients. Among patients with known infarct size (N = 1207), those with small (<4.0 cm3), medium (≥4.0 and <22.5 cm3), and large (≥22.5 cm3) infarcts started rivaroxaban a median of 2.9, 2.9, and 5.8 days, respectively, after the index IS/TIA. Recurrent IS was significantly less frequent when starting rivaroxaban ≤14 days versus ≥15 days after IS (2.0% versus 6.8%, P = 0.0034). Incidences of recurrent IS and major bleeding in whom rivaroxaban was started <3 days (N = 584) after IS were also low: 1.5% and 0.7%, respectively. Initiation of rivaroxaban administration in acute IS or TIA was associated with a low recurrence of IS (2.3%), and a low incidence of major bleeding events (0.8%) for 90 days after the index stroke. For the prevention of recurrent attacks in acute IS patients with NVAF, it is feasible to start the administration of rivaroxaban within 14 days of onset. Rivaroxaban started within 3 days of onset may be a feasible treatment option for patients with a small or medium-sized infarction.

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<![CDATA[High quality process of care increases one-year survival after acute myocardial infarction (AMI): A cohort study in Italy]]> https://www.researchpad.co/article/5c76fe0bd5eed0c484e5b33d

Background

The relationship between guideline adherence and outcomes in patients with acute myocardial infarction (AMI) has been widely investigated considering the emergency, acute, post-acute phases separately, but the effectiveness of the whole care process is not known.

Aim

The study aim was to evaluate the effect of the multicomponent continuum of care on 1-year survival after AMI.

Methods

We conducted a cohort study selecting all incident cases of AMI from health information systems during 2011–2014 in the Lazio region. Patients’ clinical history was defined by retrieving previous hospitalizations and drugs prescriptions. For each subject the probability to reach the hospital and the conditional probabilities to survive to 30 days from admission and to 31–365 days post discharge were estimated through multivariate logistic models. The 1-year survival probability was calculated as the product of the three probabilities. Quality of care indicators were identified in terms of emergency timeliness (time between residence and the nearest hospital), hospital performance in treatment of acute phase (number/timeliness of PCI on STEMI) and drug therapy in post-acute phase (number of drugs among antiplatelet, β-blockers, ACE inhibitors/ARBs, statins). The 1-year survival Probability Ratio (PR) and its Bootstrap Confidence Intervals (BCI) between who were exposed to the highest level of quality of care (timeliness<10', hospitalization in high performance hospital, complete drug therapy) and who exposed to the worst (timeliness≥10', hospitalization in low performance hospital, suboptimal drug therapy) were calculated for a mean-severity patient and varying gender and age. PRs for patients with diabetes and COPD were also evaluated.

Results

We identified 38,517 incident cases of AMI. The out-of-hospital mortality was 27.6%. Among the people arrived in hospital, 42.9% had a hospitalization for STEMI with 11.1% of mortality in acute phase and 5.4% in post-acute phase. For a mean-severity patient the PR was 1.19 (BCI 1.14–1.24). The ratio did not change by gender, while it moved from 1.06 (BCI 1.05–1.08) for age<65 years to 1.62 (BCI 1.45–1.80) for age >85 years. For patients with diabetes and COPD a slight increase in PRs was also observed.

Conclusions

The 1-year survival probability post AMI depends strongly on the quality of the whole multicomponent continuum of care. Improving the performance in the different phases, taking into account the relationship among these, can lead to considerable saving of lives, in particular for the elderly and for subjects with chronic diseases.

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<![CDATA[Quality of INR control and switching to non-Vitamin K oral anticoagulants between women and men with atrial fibrillation treated with Vitamin K Antagonists in Spain. A population-based, real-world study]]> https://www.researchpad.co/article/5c6c75bad5eed0c4843d0092

Background

Worldwide, there is growing evidence that quality of international normalized ratio (INR) control in atrial fibrillation patients treated with Vitamin K Antagonists (VKA) is suboptimal. However, sex disparities in population-based real-world settings have been scarcely studied, as well as patterns of switching to second-line Non-VKA oral anticoagulants (NOAC). We aimed to assess the quality of INR control in atrial fibrillation patients treated with VKA in the region of Valencia, Spain, for the whole population and differencing by sex, and to identify factors associated with poor control. We also quantified switching to Non-VKA oral anticoagulants (NOAC) and we identified factors associated to switching.

Methods

This is a cross-sectional, population-based study. Information was obtained through linking different regional electronic databases. Outcome measures were Time in Therapeutic Range (TTR) and percentage of INR determinations in range (PINRR) in 2015, and percentage of switching to NOAC in 2016, for the whole population and stratified by sex.

Results

We included 22,629 patients, 50.4% were women. Mean TTR was 62.3% for women and 63.7% for men, and PINNR was 58.3% for women and 60.1% for men (p<0.001). Considering the TTR<65% threshold, 53% of women and 49.3% of men had poor anticoagulation control (p<0.001). Women, long-term users antiplatelet users, and patients with comorbidities, visits to Emergency Department and use of alcohol were more likely to present poor INR control. 5.4% of poorly controlled patients during 2015 switched to a NOAC throughout 2016, with no sex differences.

Conclusion

The quality of INR control of all AF patients treated with VKA in 2015 in our Southern European region was suboptimal, and women were at a higher risk of poor INR control. This reflects sex disparities in care, and programs for improving the quality of oral anticoagulation should incorporate the gender perspective. Clinical inertia may be lying behind the observed low rates of switching in patient with poor INR control.

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<![CDATA[Development of a risk score for predicting the benefit versus harm of extending dual antiplatelet therapy beyond 6 months following percutaneous coronary intervention for stable coronary artery disease]]> https://www.researchpad.co/article/5c6f1498d5eed0c48467a3af

Background

Decisions on dual antiplatelet therapy (DAPT) duration should balance the opposing risks of ischaemia and bleeding. Our aim was to develop a risk score to identify stable coronary artery disease (SCAD) patients undergoing PCI who would benefit or suffer from extending DAPT beyond 6 months.

Methods

Retrospective analysis of a cohort of patients who completed 6 months of DAPT following PCI. Predictors of ischaemic and bleeding events for the 6–12 month period post-PCI were identified and a risk score was developed to estimate the likelihood of benefiting from extending DAPT beyond 6 months. Incidence of mortality, ischaemic and bleeding events for patients treated with DAPT for 6 vs. 6–12 months, was compared, stratified by strata of the risk score.

Results

The study included 2,699 patients. Over 6 months’ follow up, there were 78 (2.9%) ischaemic and 43 (1.6%) bleeding events. Four variables (heart failure, left ventricular ejection fraction ≤30%, left main or three vessel CAD, status post (s/p) PCI and s/p stroke) predicted ischemic events, two variables (age>75, haemoglobin <10 g/dL) predicted bleeding. In the lower stratum of the risk score, 6–12 months of treatment with DAPT resulted in increased bleeding (p = 0.045) with no decrease in ischaemic events. In the upper stratum, 6–12 months DAPT was associated with reduced ischaemic events (p = 0.029), with no increase in bleeding.

Conclusion

In a population of SCAD patients who completed 6 months of DAPT, a risk score for subsequent ischaemic and bleeding events identified patients likely to benefit from continuing or stopping DAPT.

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<![CDATA[Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II]]> https://www.researchpad.co/article/5c478c6dd5eed0c484bd2457

Background

Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking.

Objectives

To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation.

Methods

Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed.

Results

Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase.

Conclusions

In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions.

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<![CDATA[Temporal trends in prevalence and antithrombotic treatment among Asians with atrial fibrillation undergoing percutaneous coronary intervention: A nationwide Korean population-based study]]> https://www.researchpad.co/article/5c478c3ad5eed0c484bd0ebc

Background

We investigated the recent 10-year trends in the number of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in relation to prescription patterns of antithrombotic therapy.

Methods

We analyzed the annual prevalence of PCI and patterns of antithrombotic therapy after PCI, including antiplatelets and oral anticoagulants (vitamin K antagonists and non-vitamin K antagonist oral anticoagulants [NOACs]), in patients with AF between 2006 and 2015 by using the Korean National Health Insurance Service database. Independent factors associated with triple therapy (oral anticoagulant plus dual antiplatelet) prescription were assessed using multivariable logistic regression analysis.

Results

The number of patients with AF undergoing PCI increased gradually from 2006 (n = 2,140) to 2015 (n = 3,631) (ptrend<0.001). In 2006, only 22.7% of patients received triple therapy after PCI although 96.2% of them were indicated for anticoagulation (CHA2DS2-VASc score ≥2). The prescription rate of triple therapy increased to 38.3% in 2015 (ptrend<0.001), which was mainly attributed to a recent increment of NOAC-based triple therapy from 2013 (17.5% in 2015). Previous ischemic stroke or systemic embolism, old age, hypertension, and congestive heart failure were significantly associated with a higher triple therapy prescription rate, whereas previous myocardial infarction, PCI, and peripheral arterial disease were associated with triple therapy underuse.

Conclusions

From 2006 to 2015, the number of patients with AF undergoing PCI and the prescription rate of triple therapy increased gradually with a recent increment of NOAC-based antithrombotic therapy from 2013. Previous myocardial infarction, peripheral artery disease, and PCI were associated with underuse of triple therapy.

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<![CDATA[Quality indicators for ambulatory care for older adults with diabetes and comorbid conditions: A Delphi study]]> https://www.researchpad.co/article/5c1c0ae5d5eed0c484426dce

Background

An increasing number of people are living with multiple chronic conditions and it is unclear which quality indicators should be used to guide care for this population.

Objective

To critically appraise and select the most appropriate set of quality indicators for ambulatory care for older adults with five selected disease combinations.

Methods

A two-round web-based Delphi process was used to critically appraise and select quality of care indicators for older adults with diabetes and comorbidities. A fifteen-member Canadian expert panel with broad geographical and clinical representation participated in this study. The panel evaluated process indicators for meaningfulness, potential for improvements in clinical practice, and overall value of inclusion, while outcome indicators were evaluated for importance, modifiability and overall value of inclusion. A 70% agreement threshold was required for high consensus, and 60–69% for moderate consensus as measured on a 5-point Likert type scale.

Results

Twenty high-consensus and nineteen medium-consensus process and outcome indicators were selected for assessing care for older adults with selected disease combinations, including 1) concordant (conditions with a common management plan), 2) discordant (conditions with unrelated management plans), and 3) both types. Panelists reached rapid consensus on quality indicators for care for older adults with concordant comorbid conditions, but not for those with discordant conditions. All selected indicators assess clinical aspects of care. The feedback from the panelists emphasized the importance of developing indicators related to patient-centred aspects of care, including patient self-management, education, patient-physician relationships, and patient’s preferences.

Conclusions

The selected quality indicators are not intended to provide a comprehensive tool set for measuring quality of care for older adults with selected disease combinations. The recommended indicators address clinical aspects of care and can be used as a starting point for ambulatory care settings and development of additional quality indicators.

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<![CDATA[Moderate-intensity versus high-intensity statin therapy in Korean patients with angina undergoing percutaneous coronary intervention with drug-eluting stents: A propensity-score matching analysis]]> https://www.researchpad.co/article/5c141f07d5eed0c484d2955a

Objectives

It is unclear whether high-intensity statin therapy provides incremental clinical benefits over moderate-intensity statin therapy in Asian patients with angina. This study sought to compare the clinical outcomes of moderate- and high-intensity statin therapies in patients undergoing percutaneous coronary intervention (PCI) for angina in Korean patients.

Methods

Based on the national health insurance claims data in South Korea, patients aged 18 years or older without a known history of coronary artery disease, who underwent PCI with drug-eluting stents due to angina between 2011 and 2015, were enrolled. According to the intensity of statin therapy, patients were categorized into moderate-intensity statin therapy (n = 23,863) and high-intensity statin therapy (n = 9,073) groups. The primary endpoint, defined as a composite of all-cause death and myocardial infarction, was compared between the two groups using a propensity-score matching analysis.

Results

During the follow-up period (median, 2.0 years; interquartile range, 1.1–3.1), 1,572 patients had 1,367 deaths and 242 myocardial infarctions. After propensity-score matching, there were 8,939 matched pairs. There was no significant difference in the incidence of the primary endpoint between the two groups (adjusted hazard ratio of high-intensity statin therapy, 1.093; 95% confidence interval: 0.950–1.259; p = 0.212).

Conclusions

In Korean patients undergoing PCI with drug-eluting stents for angina, the high-intensity statin therapy did not provide additional clinical benefits over the moderate-intensity statin therapy.

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<![CDATA[Conservatively managed patients with non-ST-segment elevation acute coronary syndrome are undertreated with indicated medicines]]> https://www.researchpad.co/article/5c0841fcd5eed0c484fcb5e1

Introduction and aims

Patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are often managed conservatively. Clinical practice guidelines recommend treating these patients with the same pharmacological drugs as those who receive invasive treatment. We analyze the use of new antiplatelet drugs (NADs) and other recommended treatments in people discharged following an NSTE-ACS according to the treatment strategy used, comparing the medium-term prognosis between groups.

Methods

Prospective observational multicenter registry study in 1717 patients discharged from hospital following an ACS; 1143 patients had experienced an NSTE-ACS. We analyzed groups receiving the following treatment: No cardiac catheterization (NO CATH): n = 134; 11.7%; Cardiac catheterization without revascularization (CATH-NO REVASC): n = 256; 22.4%; percutaneous coronary intervention (PCI): n = 629; 55.0%; and coronary artery bypass graft (CABG): n = 124; 10.8%. We assessed major adverse cardiovascular events (MACE), all-cause mortality, and hemorrhagic complications at one year.

Results

NO CATH was the oldest, had the most comorbidities, and was at the highest risk for ischemic and hemorrhagic events. Few patients who were not revascularized with PCI received NADs (NO CATH: 3.7%; CATH-NO REVASC: 10.6%; PCI: 43.2%; CABG: 3.2%; p<0.001). Non-revascularized patients also received fewer beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and statins (p<0.001). At one year, MACE incidence in NO CATH group was three times that of the other groups (30.1%, p<0.001), and all-cause mortality was also much higher (26.3%, p<0.001). There were no significant differences in hemorrhagic events. Belonging to NO CATH group was an independent predictor for MACE at one year in the multivariate analysis (HR 2.72, 95% CI 1.29–5.73; p = 0.008).

Conclusions

Despite current invasive management of NSTE-ACS, patients not receiving catheterization are at very high risk for under treatment with recommended drugs, including NADs. Their medium-term prognosis is poor, with high mortality. Patients treated with PCI receive better pharmacological management, with high use of NADs.

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<![CDATA[Morphine Does Not Affect Myocardial Salvage in ST-Segment Elevation Myocardial Infarction]]> https://www.researchpad.co/article/5989dac4ab0ee8fa60bb1c4d

Recent studies have proposed intravenous (IV) morphine is associated with delayed action of antiplatelet agents in acute myocardial infarction. However, it is unknown whether morphine results in increased myocardial damage in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We investigated myocardial salvage index (MSI) to determine whether IV morphine affects myocardial injury adversely in STEMI patients undergoing primary PCI. 299 STEMI patients underwent contrast-enhanced magnetic resonance imaging a median of 3 days after PCI. Infarct size was measured on delayed-enhancement imaging, and area at risk was quantified on T2-weighted imaging. MSI was calculated as ‘[area at risk–infarct size] X 100 / area at risk’. IV morphine was administrated in 32.1% of patients. Patients treated with morphine had shorter symptom to balloon time and higher prevalence of Thrombolysis in Myocardial Infarction flow grade 0 or 1. The morphine group showed a trend toward larger MSI and infarct size and significantly greater area at risk than the non-morphine group. After propensity score matching (90 pairs), MSI was similar between the morphine and non-morphine group (46.1% versus 43.5%, P = .11), and infarct size and area at risk showed no difference. In propensity score-matched analysis, IV morphine prior to primary PCI in STEMI patients did not cause adverse impacts on myocardial salvage.

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<![CDATA[Association of the Ratio of Early Mitral Inflow Velocity to the Global Diastolic Strain Rate with a Rapid Renal Function Decline in Atrial Fibrillation]]> https://www.researchpad.co/article/5989d9d3ab0ee8fa60b64e76

The ratio of early mitral inflow velocity (E) to the global diastolic strain rate (E’sr) has been correlated with left ventricular filling pressure and predicts adverse cardiac outcomes in atrial fibrillation (AF). The relationship between the E/E’sr ratio and renal outcomes in AF has not been evaluated. This study examined the ability of the E/E’sr ratio in predicting progression to the renal endpoint, which is defined as a ≥ 25% decline in the estimated glomerular filtration rate in patients with AF. Comprehensive echocardiography was performed on 149 patients with persistent AF, and E’sr was assessed from three standard apical views using the index beat method. During a median follow-up period of 2.3 years, 63 patients (42.3%) were reaching the renal endpoint. Multivariate analysis showed that an increased E/E’sr ratio (per 10 cm) (hazard ratio, 1.230; 95% confidence interval, 1.088 to 1.391; p = 0.001) was associated with an increased renal endpoint. In a direct comparison, the E/E’sr ratio outperformed the ratio of E to early diastolic mitral annular velocity (E’) in predicting progression to the renal endpoint in both univariate and multivariate models (p ≤ 0.039). Moreover, adding the E/E’sr ratio to a clinical model and echocardiographic parameters provided an additional benefit in the prediction of progression to the renal endpoint (p = 0.006). The E/E’sr ratio is a useful parameter and is stronger than the E/E’ ratio in predicting the progression to the renal endpoint, and it may offer an additional prognostic benefit over conventional clinical and echocardiographic parameters in patients with AF.

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<![CDATA[Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study]]> https://www.researchpad.co/article/5989da30ab0ee8fa60b84324

Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes.

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<![CDATA[Another “String to the Bow” of PJ34, a Potent Poly(ADP-Ribose)Polymerase Inhibitor: An Antiplatelet Effect through P2Y12 Antagonism?]]> https://www.researchpad.co/article/5989dadaab0ee8fa60bb97f2

Background

Neuro- and vasoprotective effects of poly(ADP-ribose)polymerase (PARP) inhibition have been largely documented in models of cerebral ischemia, particularly with the potent PARP inhibitor PJ34. Furthermore, after ischemic stroke, physicians are faced with incomplete tissue reperfusion and reocclusion, in which platelet activation/aggregation plays a key role. Data suggest that certain PARP inhibitors could act as antiplatelet agents. In that context, the present in vitro study investigated on human blood the potential antiplatelet effect of PJ34 and two structurally different PARP inhibitors, DPQ and INO-1001.

Methods and results

ADP concentrations were chosen to induce a biphasic aggregation curve resulting from the successive activation of both its receptors P2Y1 and P2Y12. In these experimental conditions, PJ34 inhibited the second phase of aggregation; this effect was reduced by incremental ADP concentrations. In addition, in line with a P2Y12 pathway inhibitory effect, PJ34 inhibited the dephosphorylation of the vasodilator stimulated phosphoprotein (VASP) in a concentration-dependent manner. Besides, PJ34 had no effect on platelet aggregation induced by collagen or PAR1 activating peptide, used at concentrations inducing a strong activation independent on secreted ADP. By contrast, DPQ and INO-1001 were devoid of any effect whatever the platelet agonist used.

Conclusions

We showed that, in addition to its already demonstrated beneficial effects in in vivo models of cerebral ischemia, the potent PARP inhibitor PJ34 exerts in vitro an antiplatelet effect. Moreover, this is the first study to report that PJ34 could act via a competitive P2Y12 antagonism. Thus, this antiplatelet effect could improve post-stroke reperfusion and/or prevent reocclusion, which reinforces the interest of this drug for stroke treatment.

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<![CDATA[Association between Insulin Monotherapy versus Insulin plus Metformin and the Risk of All-Cause Mortality and Other Serious Outcomes: A Retrospective Cohort Study]]> https://www.researchpad.co/article/5989db3eab0ee8fa60bd5c87

Aims

To determine if concomitant metformin reduced the risk of death, major adverse cardiac events (MACE), and cancer in people with type 2 diabetes treated with insulin.

Methods

For this retrospective cohort study, people with type 2 diabetes who progressed to insulin with or without metformin from 2000 onwards were identified from the UK Clinical Practice Research Datalink (≈7% sample of the UK population). The risks of all-cause mortality, MACE and incident cancer were evaluated using multivariable Cox models comparing insulin monotherapy with insulin plus metformin. We accounted for insulin dose.

Results

12,020 subjects treated with insulin were identified, including 6,484 treated with monotherapy. There were 1,486 deaths, 579 MACE (excluding those with a history of large vessel disease), and 680 cancer events (excluding those in patients with a history of cancer). Corresponding event rates were 41.5 (95% CI 39.4–43.6) deaths, 20.8 (19.2–22.5) MACE, and 21.6 (20.0–23.3) cancer events per 1,000 person-years. The adjusted hazard ratios (aHRs) for people prescribed insulin plus metformin versus insulin monotherapy were 0.60 (95% CI 0.52–0.68) for all-cause mortality, 0.75 (0.62–0.91) for MACE, and 0.96 (0.80–1.15) for cancer. For patients who were propensity-score matched, the corresponding aHRs for all-cause mortality and cancer were 0.62 (0.52–0.75) and 0.99 (0.78–1.26), respectively. For MACE, the aHR was 1.06 (0.75–1.49) prior to 1,275 days and 1.87 (1.22–2.86) after 1,275 days post-index.

Conclusions

People with type 2 diabetes treated with insulin plus concomitant metformin had a reduced risk of death and MACE compared with people treated with insulin monotherapy. There was no statistically significant difference in the risk of cancer between people treated with insulin as monotherapy or in combination with metformin.

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<![CDATA[Duration of dual antiplatelet therapy in patients treated with percutaneous coronary intervention for coronary chronic total occlusion]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf52b

Background

The duration of dual antiplatelet therapy (DAPT) after drug-eluting stent implantation in coronary chronic total occlusion (CTO) remains unclear.

Methods

We retrospectively analyzed a total of 512 patients treated with percutaneous coronary intervention (PCI) in the Samsung Medical Center CTO registry. Patients were separated into ≤ 12-month (199, 38.9%) vs. > 12 month (313, 61.1%) based on DAPT duration with aspirin and clopidogrel. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE) during follow-up.

Results

Median follow-up duration was 67 (interquartile range: 51–84) months. MACCE occurred in 43 patients (21.6%) in the ≤ 12-month and 55 patients (17.6%) in the > 12-month groups. In the propensity-matched population, the rate of MACCE did not differ significantly between the ≤ 12-month and > 12-month group (19.4% vs. 18.8%; hazard ratio [HR], 0.95; 95% confidential interval [CI], 0.52–1.76, p = 0.88). Moreover, moderate or severe bleeding according to BARC criteria (type 2, 3 or 5) was also similar between the ≤ 12-month and > 12-month group (2.5% vs. 1.9%; HR, 1.00; 95% CI, 0.20–4.96, p = 0.99).

Conclusion

Among patients treated with PCI for CTO, DAPT with durations of ≤ 12-month showed similar long-term clinical outcomes compared to > 12-month DAPT.

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<![CDATA[Trends in the prevalence and management of pre-stroke atrial fibrillation, the South London Stroke Register, 1995-2014]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdccc4

Background

Previous studies have found low use of anticoagulation prior to stroke, in people with atrial fibrillation (AF). This study examined data on patients with AF-related stroke from a population-based stroke register, and sought to examine changes in management of AF prior to stroke, and reasons for suboptimal treatment, in those who were known to be at a high risk of stroke.

Methods

The South London Stroke Register (SLSR) is an ongoing population-based register recording first-in-a-lifetime stroke. Trends in the prevalence of AF, and antithrombotic medication prescribed before the stroke, were investigated from 1995 to 2014. Multivariable logistic regression analyses were conducted to assess the factors associated with appropriate management.

Results

Of the 5041 patients on the register, 816 (16.2%) were diagnosed with AF before their stroke. AF related stroke increased substantially among Black Carribean and Black African patients, comprising 5% of the overall cohort in 1995–1998, increasing to 25% by 2011–2014 (p<0.001). Anticoagulant prescription in AF patients at high-risk of stroke (CHADS2 score [> = 2]) increased from 9% (1995–1998) to 30% (2011–2014) (p<0.001). Antiplatelet prescription was more commonly prescribed throughout all time periods (43% to 64% of high-risk patients.) Elderly patients (>65) were significantly less likely to be prescribed an anticoagulant, with ethnicity, gender and deprivation showing no association with anticoagulation.

Conclusions

Most AF-related strokes occurred in people who could have been predicted to be at high risk before their stroke, yet were not prescribed optimal preventative treatment. The elderly,despite being at highest stroke risk, were rarely prescribed anticoagulants.

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<![CDATA[The Ratio of ADP- to TRAP-Induced Platelet Aggregation Quantifies P2Y12-Dependent Platelet Inhibition Independently of the Platelet Count]]> https://www.researchpad.co/article/5989db39ab0ee8fa60bd42e1

Objective

This study aimed to assess the association of clinical factors with P2Y12-dependent platelet inhibition as monitored by the ratio of ADP- to TRAP-induced platelet aggregation and conventional ADP-induced aggregation, respectively.

Background

Controversial findings to identify and overcome high platelet reactivity (HPR) after coronary stent-implantation and to improve clinical outcome by tailored anti-platelet therapy exist. Monitoring anti-platelet therapy ex vivo underlies several confounding parameters causing that ex vivo platelet aggregation might not reflect in vivo platelet inhibition.

Methods

In a single centre observational study, multiple electrode aggregometry was performed in whole blood of patients after recent coronary stent-implantation. Relative ADP-induced aggregation (r-ADP-agg) was defined as the ratio of ADP- to TRAP- induced aggregation reflecting the individual degree of P2Y12-mediated platelet reactivity.

Results

Platelet aggregation was assessed in 359 patients. Means (± SD) of TRAP-, ADP-induced aggregation and r-ADP-agg were 794 ± 239 AU*min, 297 ± 153 AU*min and 37 ± 14%, respectively. While ADP- and TRAP-induced platelet aggregation correlated significantly with platelet count (ADP: r = 0.302; p<0.001; TRAP: r = 0.509 p<0.001), r-ADP-agg values did not (r = -0.003; p = 0.960). These findings were unaltered in multivariate analyses adjusting for a range of factors potentially influencing platelet aggregation. The presence of an acute coronary syndrome and body weight were found to correlate with both ADP-induced platelet aggregation and r-ADP-agg.

Conclusion

The ratio of ADP- to TRAP-induced platelet aggregation quantifies P2Y12-dependent platelet inhibition independently of the platelet count in contrast to conventional ADP-induced aggregation. Furthermore, r-ADP-agg was associated with the presence of an acute coronary syndrome and body weight as well as ADP-induced aggregation. Thus, the r-ADP-agg is a more valid reflecting platelet aggregation and potentially prognosis after coronary stent-implantation in P2Y12-mediated HPR than conventional ADP-induced platelet aggregation.

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<![CDATA[Risk of Hemorrhage during Needle-Based Ophthalmic Regional Anesthesia in Patients Taking Antithrombotics: A Systematic Review]]> https://www.researchpad.co/article/5989da80ab0ee8fa60b9a26d

Background

Patients undergoing ophthalmic surgery are usually elderly and, due to systemic disease, may be on long-term therapy, such as antithrombotic agents. Rates of hemorrhagic complications associated with invasive procedures may be increased by the use of anticoagulants and antiplatelet agents.

Objective

To compare the incidence of hemorrhagic complications in patients undergoing needle-based ophthalmic regional anesthesia between patients on antithrombotic therapy and those not on such therapy.

Methods

A systematic review was conducted by two independent reviewers based on searches of Cochrane, LILACS, PubMed, Scopus, Web of Science, and the “gray” literature (Google Scholar). The end search date was May 8, 2015, across all databases.

Results

Five studies met the eligibility criteria. In three studies, individual risk of bias was low, and in two of them, moderate. In all studies, no differences regarding mild to moderate incidence of hemorrhagic complications were found between patients using antithrombotics (aspirin, clopidogrel, and warfarin) and those not using them. Rates of severe hemorrhagic complication were very low (0.04%) in both groups, supporting the safety of needle blocks, even in patients using antithrombotics. High heterogeneity across studies prevented meta-analysis. Limitations to these results include low statistical power in three experimental studies and a large 95% confidence interval in the two retrospective cohorts.

Conclusion

In this review, none of the selected studies showed significant bleeding related to needle-based ophthalmic regional anesthesia in association with the use of aspirin, clopidogrel, or vitamin K inhibitors. Since the available data is not powerful enough to provide a reliable evaluation of the true effect of antithrombotics in this setting, new studies to address these limitations are necessary.

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<![CDATA[Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting]]> https://www.researchpad.co/article/5989dae7ab0ee8fa60bbde66

Background and Purpose

Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes.

Methods

Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients.

Results

A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03–2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10–3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12–3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events.

Conclusions

PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events.

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