Impact of proton pump inhibitors on clinical outcomes in patients after acute myocardial infarction: a propensity score analysis from China Acute Myocardial Infarction(CAMI) registry

Background Proton pump inhibitors(PPIs) are recommended by the latest guidelines to reduce the risk of bleeding in acute myocardial infarction(AMI) patients treated with dual antiplatelet therapy(DAPT). However, previous pharmacodynamic and clinical studies have reported controversial results on the interaction between PPI and the P2 Y12 inhibitor clopidogrel. We investigated the impact of PPIs use on in-hospital outcomes in AMI patients, aiming to provide a new insight on the value of PPIs. Methods A total of 23,380 consecutive AMI patients who received clopidogrel with or without PPIs in the China Acute Myocardial Infarction(CAMI) registry were analyzed. The primary endpoint was major adverse cardiovascular and cerebrovascular events(MACCE) defined as a composite of in-hospital cardiac death, re-infarction and stroke. Propensity score matching(PSM) was used to control potential baseline confounders. Multivariate logistic regression analysis was performed to evaluate the effect of PPIs use on MACCE and gastrointestinal bleeding(GIB). Results Among the whole AMI population, a large majority received DAPT and 67.5% were co-medicated with PPIs. PPIs use was associated with a decreased risk of MACCE(Before PSM OR: 0.857, 95% CI: 0.742-0.990, P = 0.0359;after PSM OR: 0.862, 95% CI: 0.768-0.949, P = 0.0245) after multivariate adjustment. Patients receiving PPIs also had a lower risk of cardiac death but a higher risk of complicating with stroke. When GIB occurred, an alleviating trend of GIB severity was observed in PPIs group. Conclusions Our study is the first nation-wide large-scale study to show evidence on PPIs use in AMI patients treated with DAPT. We found that PPIs in combination with clopidogrel was associated with decreased risk for MACCE in AMI patients, and it might have a trend to mitigate GIB severity. Therefore, PPIs could become an available choice for AMI patients during hospitalization.

Efficacy and safety of a parylene-coated occluder for atrial septal defect:a prospective,multi-center,randomized controlled clinical trial

Background:Nitinol-containing devices are widely used in clinical practice.However,there are concerns about nickel release after nitinol-containing device implantation.This study aimed to compare the efficacy and safety of a parylene-coated occluder vs.a traditional nitinol-containing device for atrial septal defect(ASD).Methods:One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder(n=54)or the control group to receive a traditional occluder(n=54).The plugging success rate at 6 months after device implantation and the pre-and post-implantation serum nickel levels were compared between the two groups.A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device.The Cochran–Mantel–Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups.Results:At 6 months after implantation,successful ASD closure was achieved in 52 of 53 patients(98.11%)in both the trial and control groups(95%confidence interval(CI):[4.90,5.16])based on per-protocol set analysis.The absolute value of the lower limit of the 95%CI was 4.90%,which was less than the specified non-inferiority margin of 8%.No deaths or severe complications occurred during 6 months of follow-up.The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group(P<0.05 vs.baseline).In the trial group,there was no significant difference in the serum nickel level before vs.after device implantation(P>0.05).Conclusions:The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder.The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD,especially in patients with a nickel allergy.

A comparison of transradial and transfemoral approaches for primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients in a high volume percutaneous coronary intervention center

Background Large percutaneous coronary intervention （PCI） centers have shown statistically better prognosis with transradial approach （TRA） compared with transfemoral approach （TFA）. So we tried to compare the outcomes between TRA and TFA in one high volume PCI center in ST-segment elevation myocardial infarction （STEMI） patients undergoing primary PCI. Method Six hundred and sixty two STEMI patients who underwent primary PCI with stents implantation were retrospectively included from June 1, 2006 to April 30, 2011 in our hospital and prospectively followed for one year. The primary endpoint was defined as in-hospital net adverse clinical events （NACE） which included death, myocardial infarction （MI）, stroke, target vessel revascularization （TVR） and major bleeding. The secondary endpoint was defined as 1 year major adverse cardiovascular events （MACE） which included death, MI and TVR. Results The occurrence rates of NACE （8.0% vs. 17.0%, P = 0.0018）, access site complications （4.0% vs. 10.7% P = 0.0027） and access site-related major bleeding （2.4% vs. 6.3%, P = 0.0254） were all higher in the TFA group than in the TRA group. The incidence rate of 1 year MACE was similar between TRA and TFA （8.5% vs. 13.2%, P = 0.0932）. The inverse probabilities weighting matched multivariable Cox regression analysis showed TRA was an independent predictor of lower rates of in-hospital NACE （HR： 0.58, 95% CI： 0.34-0.99, P = 0.0477）, in-hospital death （HR： 0.31, 95% CI： 0.10-0.73, P = 0.0499） and access site complications （HR： 0.37, 95% CI： 0.19-0.73, P = 0.0040）. Conclusions TRA showed great efficacy and safety for STEMI patients undergoing primar-y PCI in high volume PCI centers. It should be recommended as routine practice in future, and especially in those patients with high risk of bleeding.

A Comparison of the Transradial and Transfemoral Approaches for the Angiography and Intervention in Patients with a History of Coronary Artery Bypass Surgery： In-hospital and 1-year Follow-up Results

Background:Percutaneous coronary intervention (PCI) through transradial approach (TRA) has shown to be safe and effective as transfemoral approach (TFA) among unselected patients.However,very few studies have compared the outcomes between TRA and TFA specifically in patients with a history of coronary artery bypass grafting surgery (CABG).Methods:A total of 404 post-CABG patients who had undergone angiography or PCI were included in the study.The primary endpoint was defined as angiographic success and procedure success.The secondary endpoint was defined as in-hospital net adverse clinical events (NACEs),which included all cause of death,myocardial infarction (MI),stroke,repeat revascularization,and major bleeding.Patients were followed-up for 1-year.Major adverse cardiovascular events (MACEs),which included death,MI,and repeat revascularization,at 1-year follow-up were also compared.Results:The angiographic success was reached by 97.4％ in the TRA group compared with 100％ in the TFA group (P =0.02).The procedure success was achieved in 99.1％ in the TRA group and 97.9％ in the TFA group (P =0.68).The incidence rates of in-hospital NACE (2.7％ vs.2.7％,P =1.00) and 1-year MACE (11.5％ vs.12.0％,P =0.88) were similar between TRA and TFA.Meanwhile,TRA was associated with a lower rate of Bleeding Academic Research Consortium ≥2 bleeding (P =0.02).In patients undergoing graft PCI,the procedure success was similar between TRA and TFA (100.0％ vs.98.7％,P =1.00).The procedure time (25.0 min vs.27.5 min,P =0.53) was also similar.No significant difference was detected between TRA and TFA in terms of in-hospital NACE (0 vs.0,P =1.00)and 1-year MACE (21.4％ vs.10.3％,P =0.19).Conclusions:Compared with TFA,TRA had lower angiographic success but had a similar procedure success in post-CABG patients.TRA was also associated with decreased bleeding and shortened hospital stay.

Combination therapy of thiamine,vitamin C and hydrocortisone in treating patients with sepsis and septic shock:a meta-analysis and trial sequential analysis

Background:The objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock.Methods:MEDLINE,EMBASE and CENTRAL databases were searched for randomized controlled trials(RCTs)that made a comparative study between the combination therapy of vitamin C and thiamine with or without hydrocortisone and the administration of placebo in patients with sepsis or septic shock.Two reviewers independently performed study selection,data extraction and quality assessment.Both short-term mortality and change in the sequential organ failure assessment(SOFA)score from baseline(delta SOFA)were set as the primary outcomes.Secondary endpoints included intensive care unit(ICU)mortality,new onset of acute kidney injury,total adverse events,ICU and hospital length of stay,duration of vasopressor usage and ventilator-free days.Meanwhile,trial sequential analysis was conducted for primary outcomes.Results:Eight RCTs with 1428 patients were included in the current study.The results showed no significant reduction of short-term mortality in sepsis and septic shock patients who received combination therapy of vitamin C and thiamine with or without hydrocortisone compared to those with placebo{risk ratio(RR),1.02[95%confidence interval(CI),0.87 to 1.20],p=0.81,I2=0%;risk difference(RD),0[95%CI,−0.04 to 0.05]}.Nevertheless,the combination therapy was associated with significant reduction in SOFA score[mean difference(MD),−0.63,(95%CI,−0.96 to−0.29,p<0.001,I^(2)=0%]and vasopressors duration(MD,−22.11[95%CI,−30.46 to−13.77],p<0.001,I2=6%).Additionally,there were no statistical differences in the pooled estimate for other outcomes.Conclusions:In the current meta-analysis,the combination therapy of vitamin C and thiamine,with or without hydrocortisone had no impact on short-term mortality when compared with placebo,but was associated with significant reduction in SOFA score among patients with sepsis and septic shock.

Incomparable Subsequent Effects between Study and Control Fluids Might Cause Questionable Results in Randomized Controlled Trials

Dr. Wiedermann commented on our systematic review and meta-regression tbr the sources of heterogeneity in trials reporting H ES 130/0.4 or 0.42 associated excess mortality in septic patients that the pooled analysis of mortality, which showed neither benefit nor harm, might be influenced by trials of low-quality. Statistically, we agree with this conclusion if two of the recruited trials judged as the intermediate risk of bias are precluded.

Comparison of Long-term Outcomes in Patients with Premature Triple-vessel Coronary Disease Undergoing Three Different Treatment Strategies： A Prospective Cohort Study

Background： Patients with premature triple-vessel disease （PTVD） have a higher risk of recurrent coronary events and repeat revascularization： however, the long-term outcome of coronary artery bypass grafting （CABG）, percutaneous coronary intervention （PCI）, and medical therapy （MT） alone for PTVD patients is controversial. The aim of this study is to evaluate the long-term outcome of PTVD patients among these three treatment strategies, to find out the most appropriate treatment methods lbr these patients. Methods： One thousand seven hundred and ninety-two patients with PTVD （age： men 〈50 years and women _〈60 years） were enrolled between 2004 and 2011. The primary end point was all-cause death. The secondary end points were cardiac death, myocardial infarction, stroke, or repeat revascularization. Results： PCI, CABG, and MT alone were performed in 933 （52.1%）, 459 （25.6%）, and 400 （22.3%） patients. Both PCI and CABG were associated with lower all-cause death （4.6% vs. 4.1% vs. 15.5%, respectively, P 〈 0.01） and cardiac death （2.8% vs. 2.0% vs. 9.8%, respectively, P 〈 0.01 ） versus MT alone. The rate of repeat revascularization in the CABG group was significantly lower than those in the PCI and MT groups. After adjusting for baseline factors, PCI and CABG were still associated with similar lower risk of all-cause death and cardiac death versus MT alone （all-cause death： hazard ratio [HR]： 0.35, 95% confidence interval [CI]： 0.23-0.53, P 〈 0.01 and HR： 0.35, 95% CI： 0.18-0.70, P= 0.003, respectively, and cardiac death： HR： 0.32, 95% CI： 0.19-0.54, P〈 0.01 and HR： 0.36, 95% CI：0.14-0.93, P = 0.03, respectively）. Conclusions： PCI and CABG provided equal long-term benefits for all-cause death and cardiac death for PTVD patients. Patients undergoing MT alone had the worst long-term clinical outcomes.

Impact of Body Mass Index on the Clinical Outcomes after Percutaneous Coronary Intervention in Patients ≥75 Years Old

Background：The impact of body mass index （BMI） on the clinical outcomes after percutaneous coronary intervention （PCI） in patients ≥75 years old remained unclear.Methods：A total of 1098 elderly patients undergoing PCI with stent implantation were recruited.Patients were divided into four groups by the value of BMI：Underweight （〈20.0 kg/m^2）,normal weight （20.0-24.9 kg/m^2）,overweight （25.0-29.9 kg/m^2） and obese （≥30.0 kg/m^2）.Major clinical outcomes after PCI were compared between the groups.The primary endpoint was defined as in-hospital major adverse cardiovascular events （MACEs）,which included death,myocardial infarction （MI） and target vessel revascularization.The secondary endpoint was defined as 1 year death.Logistic regression analysis was performed to adjust for the potential confounders.Results：Totally,1077 elderly patients with available BMIs were included in the analysis.Patients of underweight,normal weight,overweight and obese accounted for 5.6%,45.4%,41.5% and 7.5% of the population,respectively.Underweight patients were more likely to attract ST-segment elevation MI,and get accompanied with anemia or renal dysfunction.Meanwhile,they were less likely to achieve thrombolysis in MI 3 grade flow after PCI,and receive beta-blocker,angiotensin converting enzyme inhibitor or angiotensin receptor blocker after discharge.In underweight,normal weight,overweight and obese patients,in-hospital MACE were 1.7%,2.7%,3.8%,and 3.7% respectively （P =0.68）,and 1 year mortality rates were 5.0%,3.9%,5.1% and 3.7% （P =0.80）,without significant difference between the groups.Multivariate regression analysis showed that the value of BMI was not associated with in-hospital MACE in patients at 75 years old.Conclusions：The BMI ＂obese paradox＂ was not found in patients ≥75 years old.It was suggested that BMI may not be a sensitive predictor of adverse cardiovascular events in elderly patients.