Dual Therapy Group Research Articles

Safety of implantation permanent pacemaker at different times in patients with dual antiplatelet therapy

To investigate the safety of implantation permanent pacemaker (PM) at different times in patients with dual antiplatelet (DAPT) therapy after implantation of drug-eluting stent (DES). A total of 105 patients who implanted pacemakers with DAPT therapy (clopidogrel and aspirin) after implantation of DES admitted to our hospital from January 2009 to January 2015 were enrolled in the study. The patients were divided into 3 groups: dual antiplatelet therapy (DAP) group: implanting PM within 3 months after coronary stenting, continuous DAPT during perioperative period; low molecular weight heparin (LMWH) bridging group: implanting PM within 3 to 6 months after coronary stenting, DAPT interruption for 5 days replaced with subcutaneous injection of enoxaparin (1 mg/kg), twice per day, enoxaparin was stopped 12 h before operation; asprin group, implanting PM after coronary stenting 6 months, clopidogrel interruption for 5 days. Oral DAPT was returned 12-24 after operation according to the patients' condition. Peri-operative cardiovascular events and bleedings, infections were observed. There was no major adverse cardiac event (MACE) and pouch infection were observed among 3 groups in perioperation. The incidence of pocket hemorrhage and errhysis in bridging group was significantly higher than that of DAP group and asprin group (16.7%, 8.0%, 0.0% χ(2)=10.431, P=0.005 and 29.2%, 12.0%, 7.1% χ(2)=6.321, P=0.042 respectively). 3 patients had severe bleeding (12.5%, 3/24) in bridging group; compared with the other 2 groups, there were significant difference (χ(2)=9.161, P=0.010). The incidence of hematoma and hemorrhage of asprin group was lowest. LMWH bridging therapy significantly increases the risk of pacemaker pocket hematoma and hemorrhage, and the pacemaker implantation may be safer after DES implantation 6 months.

Recent advances in liver disease.

Recent advances in liver disease.

Impact of preoperative dual antiplatelet therapy on bleeding complications in patients with acute coronary syndromes who undergo urgent coronary artery bypass grafting

BackgroundA 5- to 7-day washout period before coronary artery bypass grafting (CABG) is recommended for patients who have recently received a thienopyridine derivative; however, data supporting this guideline recommendation are lacking in Japanese patients. MethodsUrgent isolated CABG was performed in 130 consecutive patients with acute coronary syndromes (ACS) (101 men; mean age, 69 years). Urgent CABG was defined as operation performed within 5 days after coronary angiography. All patients continued to receive aspirin 100mg/day. The subjects were retrospectively divided into 2 groups: 30 patients with preoperative thienopyridine (clopidogrel in 15 patients, ticlopidine in 15) exposure within 5 days [dual antiplatelet therapy (DAPT) group] and 100 patients without exposure [single antiplatelet therapy (SAPT) group]. ResultsAlthough the DAPT group had a higher proportion of patients who received perioperative platelet transfusions than the SAPT group (50% vs. 18%, p<0.001), intraoperative bleeding (median, 1100ml; interquartile range, 620–1440 vs. 920ml; 500–1100) and total drain output within 48h after surgery (577±262 vs. 543±277ml) were similar. CABG-related major bleeding, which was defined as type 4 or 5 bleeding according to the Bleeding Academic Research Consortium definitions, occurred in a significantly higher proportion of patients in the DAPT group than in the SAPT group (20% vs. 3%, p=0.005). This difference in major bleeding was driven mainly by the higher rate of transfusion of ≥5U red blood cells within a 48-h period in the DAPT group (13% vs. 1%, p=0.01). There was no significant difference in the 30-day composite endpoint including death, myocardial (re)infarction, ischemic stroke, and refractory angina between the DAPT group and SAPT group (17% vs. 19%). ConclusionsPreoperative DAPT increases the risk of CABG-related major bleeding in Japanese patients with ACS undergoing urgent CABG.

Antiplatelet Therapy of Cilostazol or Sarpogrelate with Aspirin and Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Cohort Study Using the Korean National Health Insurance Claim Database.

Background/ObjectivesAddition of cilostazol or sarpogrelate to the standard dual antiplatelet therapy of aspirin and clopidogrel has been implemented in patients that underwent percutaneous coronary intervention (PCI) with stents in Korea. This study aimed to evaluate the efficacy and safety of triple antiplatelet therapies.MethodsThis retrospective cohort study was performed using the Korean National Insurance Claim Data of the Health Insurance Review and Assessment Service from January 1, 2009 to December 31, 2014. The study cohort population consisted of patients with ischemic heart diseases and a history of PCI. They were treated with antiplatelet therapy of aspirin, clopidogrel (AC); aspirin, clopidogrel, cilostazol (ACCi); or aspirin, clopidogrel, sarpogrelate (ACSa) during the index period from January 1, 2010 to December 31, 2011. During the follow-up period up to December 31, 2014, the major adverse cardiac or cerebral events (MACCE) including death, myocardial infarction, target lesion revascularization, and ischemic stroke were assessed. Bleeding complications were also evaluated as adverse drug events.ResultsOut of 93,876 patients with PCI during the index period, 69,491 patients started dual (AC) or triple therapy (ACSa or ACCi). The clinical outcomes of comparing ACSa and ACCi therapy showed beneficial effects in the ACSa group in the prevention of subsequent cardiac or cerebral events. After Propensity score-matching between ACSa and ACCi groups, there were significant differences in MI and revascularization, with corresponding HR of 0.38 (95% CI, 0.20–0.73) and 0.66 (95% CI, 0.53–0.82) in ACSa vs. ACCi at 12 months, respectively. At the 24-month follow-up, the triple therapy groups (ACS or ACC) had a higher incidence of MACCE compared to the dual therapy (AC) group; ACSa vs. AC HR of 1.69 (95% CI, 1.62–1.77); ACC vs. AC HR of 1.22 (95% CI, 1.06–1.41). There was no significant difference in severe or life-threatening bleeding risk among three groups; ACSa vs. AC, HR of 0.68 (95% CI, 0.37–1.24), ACCi vs. AC, HR of 0.91 (95% CI, 0.77–1.09).ConclusionSarpogrelate-containing triple antiplatelet therapy demonstrated comparable rates of MACCE prevention to the conventional dual antiplatelet therapy after PCI without significantly increasing bleeding risk during the two-year follow-up period.

The Indication for Long-Term Oral Antiplatelet Therapy After Endovascular Embolization of Unruptured Intracranial Aneurysms

Background: Antiplatelet therapy (APT) is indispensable to prevent ischemic complications of unruptured intracranial aneurysms (UICAs); however, long-term APT can cause hemorrhagic complications. We evaluated the rates of use and factors for long-term APT in patients who underwent endovascular embolization of UICA. Methods: A total of 175 UICAs in 169 patients were studied. Dual APT was initiated, pre-operatively. Embolization of the UICAs was achieved with four different endovascular methods: single/double catheter (41% of the cases), balloon-assisted (50%), stent-assisted (9%), and internal trapping (2%). Single APT was utilized for 1 - 3 months in patients who were not treated with a stent. In patients who were treated with the stent-assisted method, dual APT was continued for 3 - 6 months, with transition to single APT. Results: The rates of pre-operative APT were 13%, 87%, and 0.6% in the single, dual, and triple APT therapy groups, respectively. APT was necessary for over 1 year in 18% of patients; 11% of the patients needed long-term PT because of aneurysm-specific factors (20 cases: stent placement, 16; stenosis of the branch artery of the aneurysm, one; coil protrusion to the parent artery, two; coil migration, one), and the indication was patient-specific for 7% (nine cases: coronary artery disease, five; cerebral artery disease, four). Delayed ischemic events occurred in 1.1% (two cases); one cerebral infarction was associated with stent-assisted embolization and one occurred due to stenosis of the branching artery. Conclusions: The most common indication for long-term APT was stent placement. Stenosis of the branch artery of the aneurysm, coil protrusion into the parent artery, and coil migration were the other reasons for long-term APT. The use of stents should be limited to the management of wide-neck or large aneurysms to prevent delayed ischemic and hemorrhagic complications. J Neurol Res. 2016;6(4):72-80 doi: http://dx.doi.org/10.14740/jnr390w

Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy.

BackgroundMultiple scores have been proposed to stratify bleeding risk, but their value to guide dual antiplatelet therapy duration has never been appraised. We compared the performance of the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HAS‐BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scores in 1946 patients recruited in the Prolonging Dual Antiplatelet Treatment After Grading Stent‐Induced Intimal Hyperplasia Study (PRODIGY) and assessed hemorrhagic and ischemic events in the 24‐ and 6‐month dual antiplatelet therapy groups.Methods and ResultsBleeding score performance was assessed with a Cox regression model and C statistics. Discriminative and reclassification power was assessed with net reclassification improvement and integrated discrimination improvement. The C statistic was similar between the CRUSADE score (area under the curve 0.71) and ACUITY (area under the curve 0.68), and higher than HAS−BLED (area under the curve 0.63). CRUSADE, but not ACUITY, improved reclassification (net reclassification index 0.39, P=0.005) and discrimination (integrated discrimination improvement index 0.0083, P=0.021) of major bleeding compared with HAS‐BLED. Major bleeding and transfusions were higher in the 24‐ versus 6‐month dual antiplatelet therapy groups in patients with a CRUSADE score >40 (hazard ratio for bleeding 2.69, P=0.035; hazard ratio for transfusions 4.65, P=0.009) but not in those with CRUSADE score ≤40 (hazard ratio for bleeding 1.50, P=0.25; hazard ratio for transfusions 1.37, P=0.44), with positive interaction (P int=0.05 and P int=0.01, respectively). The number of patients with high CRUSADE scores needed to treat for harm for major bleeding and transfusion were 17 and 15, respectively, with 24‐month rather than 6‐month dual antiplatelet therapy; corresponding figures in the overall population were 67 and 71, respectively.ConclusionsOur analysis suggests that the CRUSADE score predicts major bleeding similarly to ACUITY and better than HAS BLED in an all‐comer population with percutaneous coronary intervention and potentially identifies patients at higher risk of hemorrhagic complications when treated with a long‐term dual antiplatelet therapy regimen.Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00611286.

IMPS-20COMBINATION THERAPY WITH ANTI-PD-1, ANTI-TIM-3, AND FOCAL RADIATION RESULTS IN REGRESSION OF MURINE GLIOMAS

INTRODUCTION: Checkpoint molecules like programmed death-1 (PD-1) and T cell immunoglobulin mucin-3 (TIM-3) act as negative regulators of the immune system and can be upregulated in the setting of glioblastoma multiforme (GBM). Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produces long-term survivors in a murine glioma model.1 However, tumor infiltrating lymphocytes can express multiple checkpoints (including TIM-3), and expression of ≥2 checkpoints corresponds to a more exhausted T cell phenotype.2 It was therefore hypothesized that the addition of a second checkpoint-blocking antibody could achieve additive or synergistic antitumor effects. METHODS: C57BL/6 mice were implanted with mouse glioma cell line GL261 transfected with luciferase and randomized into 8 treatment arms: (1) control, (2) SRS, (3) anti-PD-1 antibody, (4) anti-TIM-3 antibody, (5) anti-PD-1 + SRS, (6) anti-TIM-3 + SRS, (7) anti-PD-1 + anti-TIM-3, and (8) anti-PD-1 + anti-TIM-3 + SRS. Overall survival was measured. Brain, cervical lymph nodes, and peripheral blood were harvested on day 21 to assess immune activation. RESULTS: Survival benefits were observed with combined anti-TIM-3 antibody + SRS compared to anti-TIM-3 antibody alone with a median survival (MS) of 69 vs. 25 days and overall survival (OS) of 50% vs. 0%, respectively (p < 0.001 by log-rank Mantel-Cox). Dual blockade with anti-TIM-3 + anti-PD-1 antibody also improved survival compared to TIM-3 blockade alone, (MS of 100 vs. 25 days, OS 60% vs. 0%, respectively, p < 0.05). Notably, OS in the triple therapy group (anti-PD-1 + anti-TIM-3 + SRS) was 100% by day 100 (p < 0.05), a significant improvement compared to all other treatment arms. Flow cytometry of organs harvested on day 21 showed that compared to the dual therapy groups, mice treated with triple therapy had increased tumor infiltration by interferon-gamma+ (IFNg) and tumor necrosis factor-alpha+ (TNFa)-producing CD4+ T cells, as well as IFNg+ CD8+ lymphocytes. CONCLUSIONS: Combining anti-TIM-3 with anti-PD-1 and radiation was synergistic and conferred a significant survival benefit.

Effect of different antiplatelet or anticoagulation therapy on postoperative pocket hematoma after electrophysiological devices placement

Objective To investigate the effect of different antiplatelet or anticoagulation therapy on postoperative pocket hematoma after electrophysiological devices placements (EPD). Methods The selected patients were taking anti-platelet or anticoagulation therapy and needed implanted permanent pacemaker, cardiac resynchronization therapy and implantable cardioversion defibrillator in our Beijing Anzhen hospital from January 2010 to January 2013. According to the type of therapy, patients were divided into 4 groups: dual anti-platelet therapy (DAP, aspirin and clopidogrel) group, low-molecular-weight heparin (LMWH, enoxaparin) bridging group, aspirin alone (ASA) group and warfarin group. The incidences of pocket hematoma after electrophysiological devices placements were observed in groups. Results A total of 324 patients were enrolled in the study. The incidence of pocket hematoma was higher in LMWH bridging group than in the other 3 groups 〔18.25% (15/81) vs. 4.93% (4/81), 3.70% (3/81), 2.47% (2/81), all P 0.05). The multiple logistic regression analysis revealed that LMWH bridging therapy was an independent risk factor for the development of pocket hematoma: patients with LMWH bridging therapy were 7 fold more likely to develop pocket hematomas than the individuals with other treatment (OR=7.124, 95% CI: 1.861-27.271). Conclusions LMWH bridging therapy increases the risk of development of pocket hematomas after electrophysiological devices placement. Key words: Aspirin; Warfarin; Heparin; Heart-assist devices; Hematoma

Benefit of initial dual-therapy on stroke prevention in Chinese hypertensive patients: a real world cohort study.

Studies have shown that combination anti-hypertensive therapy is superior to mono-therapy in blood pressure control and prevention of cardiovascular events. However, whether such advantage exists in the prevention of stroke in Chinese hypertensive patients remains unclear. This study aimed to compare the impact of initial combination versus mono-therapy on stroke events in a large cohort of Chinese hypertensive patients. Hypertensive patients with uncontrolled blood pressure and without a history of stroke were screened from the Shanghai Community-dwelling Hypertensive Population Follow-up Database. Based on the initial treatment, individuals were divided into an initial mono-therapy group and initial dual combination group. Patients were followed for 42 months. 32,682 and 4,926 patients were included in the initial mono- and dual-therapy group. The achieved target blood pressure control rates of mono vs. combination groups at 6, 12, 24, and 42 months of follow-up, were 59.47% vs. 60.05%, 78.23% vs. 77.06%, 85.51% vs. 84.02%, and 86.90% vs. 85.44%, respectively. Their corresponding incidence densities of stroke were 0.792 vs. 0.489, 1.49 vs. 1.15, 2.79 vs. 2.38, and 4.25 vs. 4.32 (cases per 100 person-year), respectively. The 6-month incidence of stroke in dual-therapy group was significantly lower than mono-therapy group (adjusted HR 0.64; 95% CI: 0.30-0.93). However, no significant group differences in the incidence density were observed at 12, 24, and 42 months. Our study demonstrates that, for patients with uncontrolled hypertension, initial dual therapy is more effective in the prevention of stroke during the first 6 months of treatment, but not thereafter. Combination antihypertensive therapy may be a beneficial initial strategy for early stroke prevention.

The safety and efficacy of antithrombotic therapy in patients undergoing cardiac rhythm device implantation: a meta-analysis.

The meta-analysis was to assess the safety and efficacy of periprocedural antithrombotic therapy and to evaluate the risk factors potentially associated with bleeding among patients undergoing cardiac implantable electronic devices implantations. A systematic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register was performed. Anticoagulation and antiplatelet therapies were assessed separately. Uninterrupted anticoagulation was associated with significant lower bleeding risk compared with heparin bridging strategy [odds ratio (OR) = 0.31, 95% confidence interval (CI) 0.18-0.53, and P < 0.0001], but there was no significant difference in thromboembolic risk between these two strategies (OR = 0.82, 95% CI 0.32-2.09, and P = 0.65). The haematoma rate was significantly increased in dual antiplatelet therapy group (OR = 6.84, 95% CI 4.16-11.25, and P < 0.00001), but not in single antiplatelet therapy (OR = 1.52, 95% CI 0.93-2.46, and P = 0.09). Clopidogrel increased the risk of haematoma vs. aspirin (OR = 2.91, 95% CI 1.27-6.69, and P = 0.01). Otherwise, a lower risk of haematoma was observed in pacemaker group vs. cardiac resynchronization therapy and/or implantable cardioverter defibrillator group (OR = 0.64, 95% CI 0.50-0.82, and P = 0.0004). This meta-analysis suggested that uninterrupted oral anticoagulation seems to be the better strategy, associated with a lower risk of bleeding complications rather than heparin bridging, and dual antiplatelet therapy carried a significant risk of bleeding whereas single antiplatelet therapy was relatively safe among patients undergoing cardiac implantable electronic devices implantations. Meanwhile, cardiac resynchronization therapy and/or implantable cardioverter defibrillator implantations increase the bleeding.

Abstract 13108: Optimal Duration of Dual Antiplatelet Therapy after Drug-Eluting Stent Implantation for Off-Label vs. On-Label Indications

Introduction: The risks and benefits of long-term dual antiplatelet therapy (DAPT) beyond 12 months in patients receiving drug-eluting stents (DES) and with high-risk clinical and angiographic features are unclear. Hypothesis: We try to determine whether extended use of DAPT is beneficial among patients with off-label use of DES. Methods: A total of 5,045 patients were included in the DES LATE trial and stratified according to randomized treatments (aspirin-alone or dual-therapy) and whether use was standard or off-label. Off-label was defined as use in renal insufficiency, ejection fraction ≤30%, acute myocardial infarction (MI), multivessel stenting, total stent length ≥36 mm, or ostial, bifurcation, grafts, left main, restenotic, thrombus, or totally occluded lesions. The primary endpoint was a composite of death from cardiac causes, MI, or stroke at 24 months after randomization. Results: Off-label use occurred in 68.6% of all patients. Among patients with off-label use, the risk of primary endpoint at 2 years was similar between aspirin-alone and dual-therapy group (2.6% vs. 3.1%; hazard ratio: 0.89; 95% confidence interval: 0.59 to 1.34, P = 0.59). In addition, no significant differences were observed between 2 treatment groups for individual and combined risks of efficacy and safety endpoints (death, MI, stroke, stent thrombosis, repeat revascularization, or major bleeding). These findings were consistent in patients with on-label use of DES (Figure). Conclusions: Extended use of DAPT beyond 12 months was not significantly more effective than aspirin monotherapy in reducing the risk of death from cardiac causes, MI, or stroke, regardless of off-label or on-label use of DES.

Dual Antiplatelets Reduce Microembolic Signals in Patients with Transient Ischemic Attack and Minor Stroke: Subgroup Analysis of CLAIR Study

Short course of dual antiplatelet therapy for early secondary prevention is a promising treatment for patients with minor stroke or transient ischemic attack at high risk of recurrence. We examined the efficacy and safety of dual antiplatelets in patients with transient ischemic attack or minor stroke, defined as National Institute of Health Stroke Scale scores 0-3, in a subgroup analysis of Clopidogrel plus aspirin versus Aspirin alone for Reducing embolization in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR) study. Microembolic signals on transcranial Doppler monitoring was used as surrogate marker for recurrent stroke risk. Patients with ≥1 microembolic signals at baseline were randomized to receive dual therapy (aspirin 75-160 mg daily and clopidogrel 300 mg day 1 then 75 mg daily) or monotherapy (aspirin 75-160 mg daily) for seven-days. Sixty-five of 100 patients recruited had transient ischemic attack or minor stroke: 30 received dual therapy and 35 received monotherapy. Mean onset-to-randomization was 2·3 days in dual therapy group and 3·2 days in monotherapy group (P = 0·03). At day 7, the proportion of patients with ≥1 microembolic signals was 9 of 29 patients in dual therapy group and 18 of 34 patients in monotherapy group (adjusted relative risk reduction 41·4%, 95% CI 29·8-51·1, P < 0·001). The median number of microembolic signals on day 7 was 0 in dual therapy group and 1·0 in monotherapy group (P = 0·046). No patients had intracranial or severe systemic hemorrhage. Early dual therapy with clopidogrel and aspirin reduces microembolic signals in patients with minor ischemic stroke or transient ischemic attack, without causing significant bleeding complications.

Clopidogrel plus aspirin versus aspirin alone for preventing early neurological deterioration in patients with acute ischemic stroke

Recent studies have suggested that combination antiplatelet therapy may be superior to monotherapy in the treatment of acute stroke. However, additional prospective studies are needed to confirm this finding. The present trial compared the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in the treatment of non-cardioembolic ischemic stroke within 72hours of onset. Six hundred and ninety patients aged ⩾40years with minor stroke or transient ischemic attack (TIA) were identified for enrollment. Experienced physicians determined baseline National Institutes of Health Stroke Scale scores at the time of admission. All patients were randomly allocated (1:1) to receive aspirin alone (300mg/day) or clopidogrel (300mg for the first day, 75mg/day thereafter) plus aspirin (100mg/day). The main endpoints were neurological deterioration, recurrent stroke, and development of stroke in patients with TIA within 14days of admission. After 43 patients were excluded, 321 patients in the dual therapy group and 326 patients in the monotherapy group completed the treatment. Baseline characteristics were similar between groups. During the 2week period, stroke deterioration occurred in nine patients in the dual therapy group and 19 patients in the monotherapy group. Stroke occurred after TIA in one patient in the dual therapy group and three patients in the monotherapy group. Similar numbers of adverse events occurred in both groups. This study showed that early dual antiplatelet treatment reduced early neurological deterioration in patients with acute ischemic stroke, compared with antiplatelet monotherapy. These results imply that dual antiplatelet therapy is superior to monotherapy in the early treatment of acute ischemic stroke.

PTH-084 Nutritional Impact Of Anti-viral Therapy Of Genotype 1 Hepatitis C Patients

IntroductionHepatitis C Virus (HCV) is a leading cause of chronic hepatitis and liver cirrhosis, with an estimated 170 million patients infected worldwide. The, UKmost common genotype of HCV is Genotype...

Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial

Daily oral triple therapy is effective at halting HIV disease progression, but can have toxic effects and is costly. We investigated whether dual therapy with lopinavir and ritonavir plus lamivudine is non-inferior to standard triple therapy. The GARDEL study (Global AntiRetroviral Design Encompassing Lopinavir/r and Lamivudine vs LPV/r based standard therapy) is a 48 week, phase 3, randomised, controlled, open-label, non-inferiority trial in antiretroviral-therapy-naive adults (age ≥18 years) with documented HIV-1 RNA viral load of at least 1000 copies per mL. The study was done at 19 centres in six countries. Patients were randomly assigned (1:1) to dual therapy or triple therapy by sealed envelopes, in blocks of four, stratified by baseline viral load (<100,000 vs ≥100,000 copies per mL). Dual therapy consisted of lopinavir 400 mg and ritonavir 100 mg plus lamivudine 150 mg, both twice daily. Triple therapy consisted of lopinavir 400 mg and ritonavir 100 mg twice daily and lamivudine or emtricitabine plus another nucleoside reverse transcriptase inhibitor (NRTI) in fixed-dose combination. Efficacy was analysed in all participants who received at least one dose of study drug. The primary endpoint was virological response rate, defined as the proportion of patients with HIV RNA less than 50 copies per mL at 48 weeks. Dual therapy was classed as non-inferior to triple therapy if the lower bound of the 95% CI for the difference between groups was no lower than -12%. Patients and investigators were unmasked to treatment allocation. This study is registered with ClinicalTrials.gov, number NCT01237444. Between Dec 10, 2010, and May 15, 2012, 217 patients were randomly assigned to the dual-therapy group and 209 to the triple-therapy group. 198 patients in the dual-therapy group and 175 in the triple-therapy group completed 48 weeks of treatment. At week 48, 189 patients (88·3%) in the dual-therapy group and 169 (83·7%) in the triple-therapy group had viral response (difference 4·6%, 95% CI -2·2 to 11·8; p=0·171). Patients with baseline viral load of at least 100,000 copies per mL showed similar results (87·2% vs 77·9%, respectively; difference 9·3%, 95% CI -2·8 to 21·5; p=0·145). Toxicity-related or tolerability-related discontinuations were more common in the triple-therapy group (n=10 [4·9%]) than in the dual-therapy group (n=1 [0·4%]; difference 4·5%, 95% CI -8·1 to -0·9; p=0·011). 65 adverse events in the dual-therapy group and 88 in the triple-therapy group were possibly or probably drug related (p=0·007). Two serious adverse events occurred, both in the dual-therapy arm, one of which (a case of gastritis) was reported as possibly or probably related to drug treatment. Dual therapy with lopinavir and ritonavir plus lamivudine regimen warrants further clinical research and consideration as a potential therapeutic option for antiretroviral-therapy-naive patients. Fundación Huésped and AbbVie.

Optimal Duration of Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation

Background— The risks and benefits of long-term dual antiplatelet therapy remain unclear. Methods and Results— This prospective, multicenter, open-label, randomized comparison trial was conducted in 24 clinical centers in Korea. In total, 5045 patients who received drug-eluting stents and were free of major adverse cardiovascular events and major bleeding for at least 12 months after stent placement were enrolled between July 2007 and July 2011. Patients were randomized to receive aspirin alone (n=2514) or clopidogrel plus aspirin (n=2531). The primary end point was a composite of death resulting from cardiac causes, myocardial infarction, or stroke 24 months after randomization. At 24 months, the primary end point occurred in 57 aspirin-alone group patients (2.4%) and 61 dual-therapy group patients (2.6%; hazard ratio, 0.94; 95% confidence interval, 0.66–1.35; P =0.75). The 2 groups did not differ significantly in terms of the individual risks of death resulting from any cause, myocardial infarction, stent thrombosis, or stroke. Major bleeding occurred in 24 (1.1%) and 34 (1.4%) of the aspirin-alone group and dual-therapy group patients, respectively (hazard ratio, 0.71; 95% confidence interval, 0.42–1.20; P =0.20). Conclusions— Among patients who were on 12-month dual antiplatelet therapy without complications, an additional 24 months of dual antiplatelet therapy versus aspirin alone did not reduce the risk of the composite end point of death from cardiac causes, myocardial infarction, or stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01186146.

Clinical impact of dual antiplatelet therapy on peptic ulcer disease

Increased incidence of coronary artery disease has led to the increased use of dual antiplatelet therapy composed of aspirin and clopidogrel. We investigated the incidence of gastrointestinal complications in patients who received single or dual antiplatelet therapy and analyzed their clinical characteristics in order to predict the prognostic factors. Between January 2009 and December 2011, we retrospectively reviewed the medical records of patients who underwent coronary angiography at Chung-Ang University Hospital (Seoul, Korea). One hundred and ninety-four patients were classified into two groups: aspirin alone group and dual antiplatelet group. Clinical characteristics, past medical history, and presence of peptic ulcer were analyzed. During the follow-up period, 11 patients had duodenal ulcer; the event rate was 2.02% in the aspirin alone group and 9.47% in the dual antiplatelet group (hazard ratio [HR] 5.24, 95% CI 1.03-26.55, p<0.05). There was no significant difference in the rate of significant upper gastrointestinal bleeding: 0% vs. 4.2% (p=0.78). In patients who received proton pump inhibitor (PPI), 24 patients had gastric ulcer; the event rate was significantly different between the two groups: 4.87% vs. 22.98% (HR 3.40, 95% CI 1.02-11.27, p<0.05). Dual antiplatelet groups had a higher incidence of duodenal ulcers without significant bleeding compared with the aspirin alone group. In patients who received PPI, the dual antiplatelet therapy group had a higher incidence of gastric ulcers without significant bleeding compared with the aspirin alone group. Therefore, physicians must pay attention to high risk groups who receive dual antiplatelet therapy and aggressive diagnostic endoscopy should also be considered.

Antiplatelet Therapy Strategies After Percutaneous Coronary Intervention in Patients Needing Oral Anticoagulation

Long-term oral anticoagulant (OAC) and dual-antiplatelet therapy are commonly needed in patients with atrial fibrillation and in patients undergoing percutaneous coronary intervention (PCI), respectively. The combination of atrial fibrillation and PCI is frequent, and leads to a dilemma for antithrombotic therapy, where risk of stroke or stent thrombosis must be balanced with bleeding risk. In the WOEST study, 573 patients on OAC undergoing PCI were randomly assigned to receive clopidogrel alone or clopidogrel plus aspirin. The primary end point was the occurrence of any bleeding episode during 1-year follow-up. Clopidogrel alone administered to patients taking OAC after PCI was associated with a significantly lower rate of bleeding complications than clopidogrel plus aspirin. Moreover, a composite secondary end point of death, myocardial infarction and stent thrombosis was significantly lower in the dual-therapy group compared with the triple-therapy group. In spite of its limitations, the WOEST study constitutes a major breakthrough, showing that long-term aspirin after PCI may be obsolete in certain circumstances. This needs to be confirmed in further studies.

Incremental benefits of repeated mesenchymal stromal cell administration compared with solitary intervention after myocardial infarction

Background aimsTraditionally, stem cell therapy for myocardial infarction (MI) has been administered as a single treatment in the acute or subacute period after MI. These time intervals coincide with marked differences in the post-infarct myocardial environment, raising the prospect that repeat cell dosing could provide incremental benefit beyond a solitary intervention. This prospect was evaluated with the use of mesenchymal stromal cells (MSCs). MethodsThree groups of rats were studied. Single-therapy and dual-therapy groups received allogeneic, prospectively isolated MSCs (1 × 106 cells) by trans-epicardial injection immediately after MI, with additional dosing 1 week later in the dual-therapy cohort. Control animals received cryopreservant solution only. Left ventricular (LV) dimensions and ejection fraction (EF) were assessed by cardiac magnetic resonance immediately before MI and at 1, 2 and 4 weeks after MI. ResultsImmediate MSC treatment attenuated early myocardial damage with EF of 35.3 ± 3.1% (dual group, n = 12) and 35.2 ± 2.2% (single group, n = 15) at 1 week after MI compared with 22.1 ± 1.9% in controls (n = 17, P < 0.01). In animals receiving a second dose of MSCs, EF increased to 40.7 ± 3.1% by week 4, which was significantly higher than in the single-therapy group (EF 35.9 ± 1.8%, P < 0.05). Dual MSC treatment was also associated with greater myocardial mass and arteriolar density, with trends toward reduced myocardial fibrosis. These incremental benefits were especially observed in remote (non-infarct) segments of LV myocardium. ConclusionsRepeated stem cell intervention in both the acute and the sub-acute period after MI provides additional improvement in ventricular function beyond solitary cell dosing, largely owing to beneficial changes remote to the area of infarction.

Comparison of Two Antiplatelet Therapy Strategies in Patients Undergoing Transcatheter Aortic Valve Implantation

Dual antiplatelet therapy is commonly used in patients undergoing transcatheter aortic valve implantation (TAVI), but the optimal antiplatelet regimen is uncertain and remains to be determined. The objective of this study was to compare 2 strategies of antiplatelet therapy in patients undergoing TAVI. A strategy using monoantiplatelet therapy (group A, n = 164) was prospectively compared with a strategy using dual antiplatelet therapy (group B, n = 128) in 292 consecutive patients undergoing TAVI. The primary end point was a combination of mortality, major stroke, life-threatening bleeding (LTB), myocardial infarction, and major vascular complications at 30 days. All adverse events were adjudicated according to the Valve Academic Research Consortium. The primary end point occurred in 22 patients (13.4%) in the group A and in 30 patients (23.4%) in the group B (hazard ratio 0.51, 95% confidence interval 0.28 to 0.94, p = 0.026). LTB (3.7% vs 12.5%, p = 0.005) and major bleedings (2.4% vs 13.3%, p <0.0001) occurred less frequently in the group A, whereas the incidence of stroke (1.2% vs 4.7%, p = 0.14) and myocardial infarction (1.2% vs 0.8%, p = 1.0) was not significantly different between the 2 groups. The benefit of a strategy using mono versus dual antiplatelet therapy persisted after multivariate adjustment and propensity score analysis (hazard ratio 0.53, 95% confidence interval 0.28 to 0.95, p = 0.033). In conclusion, a strategy using mono versus dual antiplatelet therapy in patients undergoing TAVI reduces LTB and major bleedings without increasing the risk of stroke and myocardial infarction. The results of our study question the justification of dual antiplatelet therapy and require confirmation in a randomized trial.