Antithrombotic therapy in patients undergoing TAVI: an overview of Dutch hospitals

Purpose

To assess current antithrombotic treatment strategies in the Netherlands in patients undergoing transcatheter aortic valve implantation (TAVI).

Methods

For every Dutch hospital performing TAVI (n = 14) an interventional cardiologist experienced in performing TAVI was interviewed concerning heparin, aspirin, thienopyridine and oral anticoagulation treatment in patients undergoing TAVI.

Results

The response rate was 100 %. In every centre, a protocol for antithrombotic treatment after TAVI was available. Aspirin was prescribed in all centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of concomitant clopidogrel was 3 months in over two-thirds of cases. In 2 centres, duration of concomitant clopidogrel was based upon type of prosthesis: 6 months versus 3 months for supra-annular and intra-annular prostheses, respectively.

Conclusions

Leaning on a small basis of evidence and recommendations, the antithrombotic policy for patients undergoing TAVI is highly variable in the Netherlands. As a standardised regimen might further reduce haemorrhagic complications, large randomised clinical trials may help to establish the most appropriate approach.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-013-0496-6) contains supplementary material, which is available to authorized users.     

Efficacy and Safety of Adding Clopidogrel to Aspirin on Stroke Prevention among High Vascular Risk Patients: A Meta-Analysis of Randomized Controlled Trials

Objectives

Whether clopidogrel should be added to aspirin for stroke prevention remained controversial for the risk of hemorrhagic complications. This meta-analysis was aimed to assess the efficacy and safety of adding clopidogrel to aspirin on stroke prevention in high vascular risk patients, and to provide evidence for a suitable duration of dual antiplatelet therapy.

Methods

We searched PubMed, EMBase, OVID and Cochrane Central Register of Controlled Trials (up to June, 2013) for randomized controlled trials evaluating the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in high vascular risk patients. Comparisons of stroke and hemorrhagic complications between treatment groups were expressed by the pooled Relative Risks (RRs) with 95% Confidence Intervals (CIs).

Results

Fifteen trials with a total of 97692 intention-to-treat participants were included with duration of follow-up ranging from 7 days to 3.6 years. Dual antiplatelet therapy reduced all stroke by 21% (RR: 0.79, 95% CI: 0.73–0.85) with no evidence of heterogeneity across the trials (P = 0.27, I ² = 17%).The effects were consistent between short-term subgroup (≤1 month, RR: 0.76, 95% CI: 0.67–0.85) and long-term subgroup (≥3 months, RR: 0.81, 95% CI: 0.73–0.89). The risk of major bleeding was not significantly increased by dual antiplatelet therapy in short-term subgroup (RR: 1.11, 95% CI: 0.91–1.36), while significantly increased in long-term subgroup (RR: 1.52, 95% CI: 1.36–1.69). Long-term dual antiplatelet therapy substantially increased the risk of intracranial bleeding (RR: 1.76, 95% CI: 1.22–2.54).

Conclusions

This meta-analysis demonstrates that short-term combination of clopidogrel and aspirin is effective and safe for stroke prevention in high vascular risk patients. Long-term combination therapy substantially increases the risk of major bleeding and intracranial bleeding.     

Clopidogrel and Aspirin versus Aspirin Alone for Stroke Prevention: A Meta-Analysis

Background and Purpose

Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta-analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone.

Methods

Randomized controlled trials were searched in PubMed (1966-May, 2015), EMBASE (1947-May, 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (1948-May, 2015), WHO International Clinical Trial (ICTRP) (2004-May, 2015), China Biology Medicine disc (CBM disc) (1978-May, 2015) and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR) was pooled with 95% confidence interval (CI) for dichotomous data. The heterogeneity was considered significant if the χ² test was significant (P value < 0.10) or the I² > 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region.

Results

We included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59–0.82, P <0.05; RR = 0.84, 95% CI: 0.72–0.98, P = 0.03, respectively). With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03–2.23, P = 0.04; RR = 1.54, 95% CI: 1.32–1.79, P<0.05, respectively).

Conclusions

Dual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding.     

Safety of Low-Dose Aspirin in Endovascular Treatment for Intracranial Atherosclerotic Stenosis

Objectives

To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

Methods

From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention.

Results

Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5%) with acute thrombosis, 5 patients (1.8%) with subacute thrombosis, 17 patients (6.2%) with stroke, and 2 death (0.7%) in low-dose aspirin group, compared with no patient (0%) with acute thrombosis, 2 patient (2.1%) with subacute thrombosis, 6 patients (6.2%) with stroke, and 2 death (2.1%) in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups.

Conclusion

Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.     

High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel

Background

Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.

Objectives

To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).

Patients

Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.

Results

At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.

Conclusions

Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.

Trial Registration

ClinicalTrials.gov NCT01339026     

Impact of Antithrombotic Therapy in Atrial Fibrillation on the Presentation of Coronary Artery Disease

Background

Little is known about whether atrial fibrillation is a presentation of coronary disease. There is a paucity of knowledge about their causal relationship and also the impact of different antithrombotic strategies on the subsequent presentation of symptomatic coronary disease.

Methods and Results

We studied 7,526 Chinese patients diagnosed with non-valvular atrial fibrillation and no documented history of coronary artery disease. The primary endpoint was the new occurrence of coronary artery disease—either stable coronary artery disease or acute coronary syndrome. After a mean follow-up of 3.2±3.5 years (24,071 patient-years), a primary endpoint occurred in 987 patients (13.1%). The overall annual incidence of coronary artery disease was 4.10%/year. No significant differences in age, sex, and mean CHA₂DS₂-VASc score were observed between patients with and without the primary endpoint. When stratified according to the antithrombotic strategies applied for stroke prevention, the annual incidence of coronary artery disease was 5.49%/year, 4.45%/year and 2.16%/year respectively in those prescribed no antithrombotic therapy, aspirin, and warfarin. Similar trends were observed in patients with acute coronary syndromes. Diabetes mellitus, smoking history and renal failure requiring dialysis were predictors for primary endpoint in all antithrombotic therapies.

Conclusion

In patients with non-valvular atrial fibrillation, there is a modest association with coronary artery disease. Patients prescribed warfarin had the lowest risk of new onset coronary artery disease.     

The Efficacy and Adverse Reaction of Bleeding of Clopidogrel plus Aspirin as Compared to Aspirin Alone after Stroke or TIA: A Systematic Review

Background and Purpose

Given the high risk of stroke after TIA (transient ischemia attack) or stroke and the adverse reaction of bleeding of antiplatelets, we undertook a meta-analysis, reviewed randomized controlled trials (RCTs) comparing aspirin plus clopidogrel with aspirin alone to determine the efficacy and adverse reaction of bleeding of the two protocols in the prevention of stroke.

Methods

We analyzed the incidences of stroke, bleeding and severe bleeding by using fixed-effect model or random-effect model on the basis of the result of heterogeneity test.

Results

Five qualified RCTs satisfied the inclusion criteria. We found that treatment with aspirin plus clopidogrel was associated with lower incidence of stroke (Risk Ratio (RR), 0.66, 95% confidence interval (CI), 0.47 to 0.93), higher incidence of bleeding (RR, 1.75, 95% CI, 1.48 to 2.05) as compared with aspirin-alone treatment. In terms of severe bleeding, no statistical difference existed between them (RR, 2.21, 95% CI, 0.25 to 19.52).

Conclusion

The combined use of aspirin and clopidogrel is more effective than aspirin alone for patients with previous TIA or stroke for the prevention of stroke, with risk of bleeding being higher. No statistical difference was found in severe bleeding between the two treatment protocols.     

Re-Infection Outcomes following One- and Two-Stage Surgical Revision of Infected Hip Prosthesis: A Systematic Review and Meta-Analysis

Background

The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option; however, its effectiveness in comparison to the two-stage strategy remains uncertain.

Objective

To compare the effectiveness of one- and two-stage revision strategies in treating prosthetic hip infection, using re-infection as an outcome.

Design

Systematic review and meta-analysis.

Data Sources

MEDLINE, EMBASE, Web of Science, Cochrane Library, manual search of bibliographies to March 2015, and email contact with investigators.

Study Selection

Cohort studies (prospective or retrospective) conducted in generally unselected patients with prosthetic hip infection treated exclusively by one- or two-stage revision and with re-infection outcomes reported within two years of revision. No clinical trials were identified.

Review Methods

Data were extracted by two independent investigators and a consensus was reached with involvement of a third. Rates of re-infection from 38 one-stage studies (2,536 participants) and 60 two-stage studies (3,288 participants) were aggregated using random-effect models after arcsine transformation, and were grouped by study and population level characteristics.

Results

In one-stage studies, the rate (95% confidence intervals) of re-infection was 8.2% (6.0–10.8). The corresponding re-infection rate after two-stage revision was 7.9% (6.2–9.7). Re-infection rates remained generally similar when grouped by several study and population level characteristics. There was no strong evidence of publication bias among contributing studies.

Conclusion

Evidence from aggregate published data suggest similar re-infection rates after one- or two-stage revision among unselected patients. More detailed analyses under a broader range of circumstances and exploration of other sources of heterogeneity will require collaborative pooling of individual participant data.

Systematic Review Registration

PROSPERO 2015: CRD42015016559     

Aspirin Use and Lung Cancer Risk: A Possible Relationship? Evidence from an Updated Meta-Analysis

Background and Purpose

Growing evidence has emerged and controversial results reported on possible relationship between aspirin use and lung cancer risk. We, therefore, conducted this updated and comprehensive meta-analysis to evaluate this issue, with focus on dose-risk and duration-risk relationships.

Methods

We searched electronic databases including PUBMED, EMBASE and Cochrane library to identify eligible studies. Relative risk (RR) and its 95% confidence interval (CI) were used for cohort studies, while odds ratio (OR) were employed for case-control studies. The random effects and fixed effects models were used for analyses.

Results

18 studies were identified including 19835 lung cancer cases, which were eligible for inclusion in the present meta-analysis. Pooled data from case-control studies showed a significant inverse association between regular aspirin use and lung cancer risk. But for cohort studies, insignificant association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI: 0.95 – 1.16; I²: 10.3%, p value: 0.351). In case-control studies, standard aspirin use (>325mg) was related to lower lung cancer incidence, compared with low-dose aspirin use (75–100mg). A similar trend was observed in cohort studies. Besides, when analysis was restricted to long time regular aspirin use (>5 years), insignificant results were reported in both cohort and case-control studies. Finally, regular aspirin use might result in higher reduction of non-small cell lung cancer incidence among men.

Conclusions

Our findings do not support the protective effect of regular aspirin use on lung cancer risk. Long time aspirin use, sex, dose and type of lung cancer might alter the effect of aspirin use on lung cancer risk. More well-designed studies are needed to further clarify these associations.     

Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting

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.     

Comparison of a New P2Y12 Receptor Specific Platelet Aggregation Test with Other Laboratory Methods in Stroke Patients on Clopidogrel Monotherapy

Background

Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel.

Objectives

To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitoring clopidogrel therapy.

Patients/Methods

Study population included 111 patients with the history of ischemic stroke being on clopidogrel monotherapy and 140 controls. The effect of clopidogrel was tested by a newly developed ADP(PGE1) aggregation test in which prostaglandin E1 treated platelets are used. Results of conventional ADP induced platelet aggregation, VerifyNow P2Y12 assay and ADP(PGE1) aggregation were compared to those obtained by flow cytometric analysis of vasodilator stimulated phosphoprotein (VASP) phosphorylation. Reference intervals for all assays were determined according to the guidelines of Clinical Laboratory Standards Institute.

Results

The P2Y12-specificity of ADP(PGE1) test was proven by comparing it with ADP aggregation in the presence of P2Y1 antagonist, adenosine 3’, 5’-diphosphate. The method was not influenced by aspirin treatment. Approximately 50% of patients were clopidogrel resistant by conventional ADP aggregation and VerifyNow tests. The ADP(PGE1) method and the VASP phosphorylation assay identified 25.9% and 11.7% of patients as non-responders, respectively. ADP(PGE1) aggregation showed good correlation with VASP phosphorylation and had high diagnostic efficiency.

Conclusion

The new ADP(PGE1) method is a reliable test for monitoring P2Y12 receptor inhibition by platelet aggregation. As a subset of patients are non-responders, monitoring clopidogrel therapy by adequate methods is essential.     

A Comparison of Technique Modifications in Laparoscopic Donor Nephrectomy: A Systematic Review and Meta-Analysis

Objective

To compare the effectiveness of different technique modifications in laparoscopic donor nephrectomy.

Design

Systematic review and meta-analyses.

Data Sources

Searches of PubMed, EMBASE, Web of Science and Central from January 1st 1997 until April 1st 2014.

Study Design

All cohort studies and randomized clinical trials comparing fully laparoscopic donor nephrectomy with modifications of the standard technique including hand-assisted, retroperitoneoscopic and single port techniques, were included.

Data-Extraction and Analysis

The primary outcome measure was the number of complications. Secondary outcome measures included: conversion to open surgery, first warm ischemia time, estimated blood loss, graft function, operation time and length of hospital stay. Each technique modification was compared with standard laparoscopic donor nephrectomy. Data was pooled with a random effects meta-analysis using odds ratios, weighted mean differences and their corresponding 95% confidence intervals. To assess heterogeneity, the I2 statistic was used. First, randomized clinical trials and cohort studies were analyzed separately, when data was comparable, pooled analysis were performed.

Results

31 studies comparing laparoscopic donor nephrectomy with other technique modifications were identified, including 5 randomized clinical trials and 26 cohort studies. Since data of randomized clinical trials and cohort studies were comparable, these data were pooled. There were significantly less complications in the retroperitoneoscopic group as compared to transperitoneal group (OR 0.52, 95%CI 0.33–0.83, I2 = 0%). Hand-assisted techniques showed shorter first warm ischemia and operation times.

Conclusions

Hand-assistance reduces the operation and first warm ischemia times and may improve safety for surgeons with less experience in laparoscopic donor nephrectomy. The retroperitoneoscopic approach was significantly associated with less complications. However, given the, in general, poor to intermediate quality and considerable heterogeneity in the included studies, further high-quality studies are required.

Trial Registration

The review protocol was registered in the PROSPERO database before the start of the review process (CRD number 42013006565).     

Aspirin Compared to Low Intensity Anticoagulation in Patients with Non-Valvular Atrial Fibrillation. A Systematic Review and Meta-Analysis

Background

Despite its lack of efficacy, aspirin is commonly used for stroke prevention in atrial fibrillation. Since prior studies have suggested a benefit of low-intensity anticoagulation over aspirin in the prevention of vascular events, the aim of this systematic review was to compare the outcomes of patients with non-valvular atrial fibrillation treated with low-intensity anticoagulation with Vitamin K antagonists or aspirin.

Methods

We conducted a systematic review searching Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, from 1946 to October 14^th, 2015. Randomized controlled trials were included if they reported the outcomes of patients with non-valvular atrial fibrillation treated with a low-intensity anticoagulation compared to patients treated with aspirin. The primary outcome was a combination of ischemic stroke or systemic embolism. The random-effects model odds ratio was used as the outcome measure.

Results

Our initial search identified 6309relevant articles of which three satisfied our inclusion criteria and were included. Compared to low-intensity anticoagulation, aspirin alone did not reduce the incidence of ischemic stroke or systemic embolism OR 0.94 (95% CI 0.57–1.56), major bleeding OR 1.06 (95% CI 0.42–2.62) or vascular death OR 1.04 (95% CI 0.61–1.75). The use of aspirin was associated with a significant increase in all-cause mortality OR 1.66 (95% CI 1.12–2.48).

Conclusion

In patients with non-valvular atrial fibrillation, aspirin provides no benefits over low-intensity anticoagulation. Furthermore, the use of aspirin appears to be associated with an increased risk in all-cause mortality. Our study provides more evidence against the use aspirin in patients with non-valvular atrial fibrillation.     

Impact of Aspirin and Clopidogrel Interruption on Platelet Function in Patients Undergoing Major Vascular Surgery

Aims

To investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption.

Methods/Results

We conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group). The antiplatelet drugs were withdrawn five days before surgery (baseline) and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin) and ADP (clopidogrel) and by VASP assay (clopidogrel). Platelet-leukocyte complex (PLC) level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4±10%; p = 0.16), in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10±15%; p = 0.02), compared to baseline.

Conclusions

Aspirin withdrawal 5 days before high-bleeding-risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management.     

A Short-Term Effect of Low-Dose Aspirin on Major Hemorrhagic Risks in Primary Prevention: A Case-Crossover Design

Background

Very few studies have examined the risk of short-term adverse hemorrhage of low-dose aspirin use in primary prevention. This case-crossover study examined the transient effect of low-dose aspirin use on major hemorrhagic risks.

Methods

A representative database of 1,000,000 patients randomly sampled from the Taiwan''s National Health Insurance Research Database in 2000 was analyzed. The study cohort consisted of a total of 501,946 individuals, aged 30–95 years old, at risk of a major bleeding event in 2000. A case-crossover study was used to retrieve data on 10,905 incident patients with major hemorrhagic complications (3,781 cerebral and 7,124 gastrointestinal) and prescribed low-dose aspirin (≤300 mg/day) from 2000–2008. A 56-day time window (∼2 months) was used as the case period for which the odds ratio (OR) was estimated using the ratio of patients exposed during the 56-day case period only (1–56 days before the index date) compared to its corresponding 56-day control period only (57–112 days before the index date).

Results

Four hundred eighty-nine (4.5%) of the 10,905 hemorrhagic patients had used low-dose aspirin during the 56-day case only period; 294 (2.7%) of the same patients had used low-dose aspirin during control only period. Low-dose aspirin use increase the risk of developing a major hemorrhage 1.33-fold (95% CI = 1.13–1.55, P<0.0001). Significance was found prominent in 4,453 non-hypertensive and non-diabetic subjects (Adjusted odds ratio  = 1.88, 95% CI = 1.21–2.91).

Conclusion

Transient low-dose aspirin use increases risk for major hemorrhagic events in Han Chinese.     

Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis

Background

Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.

Objective

A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.

Data Sources

MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.

Study Selection

Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.

Data Extraction

Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.

Data Synthesis

Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11–0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69–3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40–1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.

Conclusions

VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients’ risk for recurrent PE as well as the patients’ values and preferences.     

Comorbidities against Quality Control of VKA Therapy in Non-Valvular Atrial Fibrillation: A French National Cross-Sectional Study

Background

Given the prevalence of non-valvular atrial fibrillation in the geriatric population, thromboembolic prevention by means of vitamin K antagonists (VKA) is one of the most frequent daily concerns of practitioners. The effectiveness and safety of treatment with VKA correlates directly with maximizing the time in therapeutic range, with an International Normalized Ratio (INR) of 2.0-3.0. The older population concentrates many of factors known to influence INR rate, particularly concomitant medications and concurrent medical conditions, also defined as comorbidities.

Objective

Determine whether a high burden on comorbidities, defined by a Charlson Comorbidity Index (CCI) of 3 or greater, is associated a lower quality of INR control.

Study-Design

Cross-sectional study.

Settings

French geriatric care units nationwide.

Participants

2164 patients aged 80 and over and treated with vitamin K antagonists.

Measurements

Comorbidities were assessed using the Charlson Comorbidity Index (CCI). The recorded data included age, sex, falls, kidney failure, hemorrhagic event, VKA treatment duration, and the number and type of concomitant medications. Quality of INR control, defined as time in therapeutic range (TTR), was assessed using the Rosendaal method.

Results

487 patients were identified the low-quality control of INR group. On multivariate logistic regression analysis, low-quality control of INR was independently associated with a CCI ≥3 (OR = 1.487; 95% CI [1.15; 1.91]). The other variables associated with low-quality control of INR were: hemorrhagic event (OR = 3.151; 95% CI [1.64; 6.07]), hospitalization (OR = 1.614, 95% CI [1.21; 2.14]).

Conclusion

An elevated CCI score (≥3) was associated with low-quality control of INR in elderly patients treated with VKA. Further research is needed to corroborate this finding.     

Estimating the Incidence of Acute Infectious Intestinal Disease in the Community in the UK: A Retrospective Telephone Survey

Objectives

To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design.

Design/Setting

A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days.

Participants

14,813 individuals for all of whom we had a legible recording of their agreement to participate

Outcomes

Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause.

Results

The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135–2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377–778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time.

Conclusions

The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates.     

Retropupillary Fixation of Iris-Claw Intraocular Lens for Aphakic Eyes in Children

Purpose

To report outcome, complications and safety of retropupillary fixated iris-claw intraocular lenses in a pediatric population.

Design

Retrospective study.

Patients and Methods

Ten consecutive pediatric patients (15 eyes) underwent placement of retropupillary fixated iris-claw intraocular lenses between October 2007 and July 2013 at the Department of Ophthalmology, Medical University Graz and General Hospital Klagenfurt, Austria. Postoperative visual acuity and complications were analyzed.

Results

Median final best-corrected visual acuity improved by 0.12 logMAR from preoperative baseline. Mean postoperative spherical equivalent was -0.05 ± 1.76 D. No serious complications were observed intra- or postoperatively during the entire follow-up period of up to 40 months. One patient experienced a haptic disenclavation with IOL subluxation immediately after a car accident.

Conclusion

Our study demonstrates that iris-claw intraocular lens implantation behind the iris is safe in children with lack of capsular support and yields excellent visual outcome with low complication rate.