nejm/jama/lancet 2015年1-2月 · patiromer in patients with kidney disease and hyperkalemia...

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读书报告 NEJM/JAMA/Lancet：2015年1-2月

四川大学华西医院ICU

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www.themegallery.com

2015年1-2月NEJM/JAMA/Lancet期刊荟萃

A Randomized Trial of Icatibant in ACE-Inhibitor–Induced Angioedema

Murat Baş, M.D., et al. N Engl J Med 2015; 372:418-425.

Ruxolitinib versus Standard Therapy for the Treatment of Polycythemia

Vera

Alessandro M. Vannucchi, M.D., et al. N Engl J Med 2015; 372:426-435.

Prehospital Use of Magnesium Sulfate as Neuroprotection in Acute

Stroke

Jeffrey L. Saver, M.D., et al. N Engl J Med 2015; 372:528-536.

Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer

Martin Schlumberger, M.D., et al. N Engl J Med 2015; 372:621-630.

Burden of Clostridium difficile Infection in the United States

Fernanda C. Lessa, M.D., et al. N Engl J Med 2015; 372:825-834.

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Estimated Life Expectancy in a Scottish Cohort With Type 1 Diabetes, 2008-

2010

Shona J. Livingstone, MSc, et al. JAMA. 2015;313(1):37-44.

Association Between 7 Years of Intensive Treatment of Type 1 Diabetes and

Long-term Mortality

Writing Group for the DCCT/EDIC Research. JAMA. 2015;313(1):45-53.

Quadrivalent HPV Vaccination and Risk of Multiple Sclerosis and Other

Demyelinating Diseases of the Central Nervous System

Nikolai Madrid Scheller, MB, et al. JAMA. 2015;313(1):54-61.

Community-Wide Cardiovascular Disease Prevention Programs and Health

Outcomes in a Rural County, 1970-2010

N. Burgess Record, MD., et al. JAMA. 2015;313(2):147-155.

Oral Iron Supplementation After Blood Donation A Randomized Clinical Trial

Joseph E. Kiss, MD, et al. JAMA. 2015;313(6):575-583.

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Blood Pressure Lowering in Type 2 Diabetes A Systematic Review and Meta-analysis

Connor A. Emdin, HBSc, et al. JAMA. 2015;313(6):603-615.

Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With

Severe Community-Acquired Pneumonia and High Inflammatory Response A

Randomized Clinical Trial

Antoni Torres, MD, PhD, et al. JAMA. 2015;313(7):677-686.

Association Between the Use of Fondaparinux vs Low-Molecular-Weight Heparin and

Clinical Outcomes in Patients With Non–ST-Segment Elevation Myocardial Infarction

Karolina Szummer, MD, PhD, et al. JAMA. 2015;313(7):707-716.

Association of NSAID Use With Risk of Bleeding and Cardiovascular Events in Patients

Receiving Antithrombotic Therapy After Myocardial Infarction

Anne-Marie Schjerning Olsen, MD, PhD,, et al. JAMA. 2015;313(8):805-814.

Anticoagulant Reversal, Blood Pressure Levels, and Anticoagulant Resumption in

Patients With Anticoagulation-Related Intracerebral Hemorrhage

Joji B. Kuramatsu, MD, et al. JAMA. 2015;313(8):824-836.

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HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence

from genetic analysis and randomized trials

Daniel I Swerdlow, et al. Lancet 2015; 385: 351–61

Long-term outcomes after stenting versus endarterectom for treatment of symptomatic

carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial

Leo H Bonati, et al. Lancet 2015; 385: 529–38.

Cardioverter defibrillator implantation without induction of ventricular fibrillation: a

single-blind, non-inferiority, randomized controlled trial

Jeff S Healey, et al. Lancet 2015; 385: 785–91.

Extended duration dual antiplatelet therapy and mortality: a systematic review and

meta-analysis

Sammy Elmariah, et al. Lancet 2015; 385: 792–98.

Standard versus atrial fibrillation-specific management strategy (SAFETY) to reduce

recurrent admission and prolong survival: pragmatic, multicentre, randomized

controlled trial

Simon Stewart, et al. Lancet 2015; 385: 775–84.

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2015年1-2月NEJM/JAMA/Lancet摘要略读

Patiromer in Patients with Kidney Disease and

Hyperkalemia Receiving RAAS Inhibitors Matthew R. Weir, M.D., et al. N Engl J Med 2015; 372:211-221.

BACKGROUND

Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin–angiotensin–aldosterone

system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed

potassium binder, in a multicenter, prospective trial.

METHODS

Patients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium

levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day)

for 4 weeks (initial treatment phase); the primary efficacy end point was the mean change in the serum

potassium level from baseline to week 4. Eligible patients at the end of week 4 (those with a baseline

potassium level of 5.5 to <6.5 mmol per liter in whom the level decreased to 3.8 to <5.1 mmol per liter)

entered an 8-week randomized withdrawal phase in which they were randomly assigned to continue

patiromer or switch to placebo; the primary efficacy end point was the between-group difference in the

median change in the serum potassium level over the first 4 weeks of that phase.

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Patiromer in Patients with Kidney Disease and

Hyperkalemia Receiving RAAS Inhibitors Matthew R. Weir, M.D., et al. N Engl J Med 2015; 372:211-221.

RESULTS

In the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium

measurement at a scheduled visit after day 3, the mean (±SE) change in the serum potassium level was

?1.01±0.03 mmol per liter (P<0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients

had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were

randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase.

The median increase in the potassium level from baseline of that phase was greater with placebo than with

patiromer (P<0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of

the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P<0.001).

Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia

occurred in 3%.

CONCLUSIONS

In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia,

patiromer treatment was associated with a decrease in serum potassium levels and, as compared with

placebo, a reduction in the recurrence of hyperkalemia.

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Sodium Zirconium Cyclosilicate in Hyperkalemia

David K. Packham, M.B., et al. N Engl J Med 2015; 372:222-231.

BACKGROUND

Hyperkalemia (serum potassium level, >5.0 mmol per liter) is associated with increased mortality

among patients with heart failure, chronic kidney disease, or diabetes. We investigated whether

sodium zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum

potassium levels in patients with hyperkalemia.

METHODS

In this multicenter, two-stage, double-blind, phase 3 trial, we randomly assigned 753 patients

with hyperkalemia to receive either ZS-9 (at a dose of 1.25 g, 2.5 g, 5 g, or 10 g) or placebo three

times daily for 48 hours. Patients with normokalemia (serum potassium level, 3.5 to 4.9 mmol

per liter) at 48 hours were randomly assigned to receive either ZS-9 or placebo once daily on

days 3 to 14 (maintenance phase). The primary end point was the exponential rate of change in

the mean serum potassium level at 48 hours.

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Sodium Zirconium Cyclosilicate in Hyperkalemia

David K. Packham, M.B., et al. N Engl J Med 2015; 372:222-231.

RESULTS

At 48 hours, the mean serum potassium level had decreased from 5.3 mmol per liter at baseline to 4.9 mmol

per liter in the group of patients who received 2.5 g of ZS-9, 4.8 mmol per liter in the 5-g group, and 4.6

mmol per liter in the 10-g group, for mean reductions of 0.5, 0.5, and 0.7 mmol per liter, respectively

(P<0.001 for all comparisons) and to 5.1 mmol per liter in the 1.25-g group and the placebo group (mean

reduction, 0.3 mmol per liter). In patients who received 5 g of ZS-9 and those who received 10 g of ZS-9,

serum potassium levels were maintained at 4.7 mmol per liter and 4.5 mmol per liter, respectively, during the

maintenance phase, as compared with a level of more than 5.0 mmol per liter in the placebo group (P<0.01

for all comparisons). Rates of adverse events were similar in the ZS-9 group and the placebo group (12.9%

and 10.8%, respectively, in the initial phase; 25.1% and 24.5%, respectively, in the maintenance phase).

Diarrhea was the most common complication in the two study groups.

CONCLUSIONS

Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a

significant reduction in potassium levels at 48 hours, with normokalemia maintained during 12 days of

maintenance therapy.

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Factor XI Antisense Oligonucleotide for Prevention of Venous

Thrombosis Harry R. Büller, M.D., et al. N Engl J Med 2015; 372:232-240.

BACKGROUND

Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing

bleeding, but the role of factor XI in the prevention of postoperative venous thrombosis in

humans is unknown. FXI-ASO (ISIS 416858) is a second-generation antisense oligonucleotide

that specifically reduces factor XI levels. We compared the efficacy and safety of FXI-ASO with

those of enoxaparin in patients undergoing total knee arthroplasty.

METHODS

In this open-label, parallel-group study, we randomly assigned 300 patients who were undergoing

elective primary unilateral total knee arthroplasty to receive one of two doses of FXI-ASO (200

mg or 300 mg) or 40 mg of enoxaparin once daily. The primary efficacy outcome was the

incidence of venous thromboembolism (assessed by mandatory bilateral venography or report of

symptomatic events). The principal safety outcome was major or clinically relevant nonmajor

bleeding.

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Factor XI Antisense Oligonucleotide for Prevention of Venous

Thrombosis Harry R. Büller, M.D., et al. N Engl J Med 2015; 372:232-240.

RESULTS

Around the time of surgery, the mean (±SE) factor XI levels were 0.38±0.01 units per milliliter

in the 200-mg FXI-ASO group, 0.20±0.01 units per milliliter in the 300-mg FXI-ASO group,

and 0.93±0.02 units per milliliter in the enoxaparin group. The primary efficacy outcome

occurred in 36 of 134 patients (27%) who received the 200-mg dose of FXI-ASO and in 3 of 71

patients (4%) who received the 300-mg dose of FXI-ASO, as compared with 21 of 69 patients

(30%) who received enoxaparin. The 200-mg regimen was noninferior, and the 300-mg regimen

was superior, to enoxaparin (P<0.001). Bleeding occurred in 3%, 3%, and 8% of the patients in

the three study groups, respectively.

CONCLUSIONS

This study showed that factor XI contributes to postoperative venous thromboembolism;

reducing factor XI levels in patients undergoing elective primary unilateral total knee

arthroplasty was an effective method for its prevention and appeared to be safe with respect to

the risk of bleeding.

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Less-Tight versus Tight Control of Hypertension in Pregnancy Laura A. Magee, M.D., et al. N Engl J Med 2015; 372:407-417.

BACKGROUND

The effects of less-tight versus tight control of hypertension on pregnancy complications are

unclear.

METHODS

We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33

weeks 6 days of gestation who had nonproteinuric preexisting or gestational hypertension, office

diastolic blood pressure of 90 to 105 mm Hg (or 85 to 105 mm Hg if the woman was taking

antihypertensive medications), and a live fetus. Women were randomly assigned to less-tight

control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood

pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal

care for more than 48 hours during the first 28 postnatal days. The secondary outcome was

serious maternal complications occurring up to 6 weeks post partum or until hospital discharge,

whichever was later.

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Less-Tight versus Tight Control of Hypertension in Pregnancy Laura A. Magee, M.D., et al. N Engl J Med 2015; 372:407-417.

RESULTS

Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-

outcome rates were similar among 493 women assigned to less-tight control and 488 women

assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95%

confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7%

and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic

blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4).

Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-

control group and 27.5% of the women in the tight-control group (P<0.001).

CONCLUSIONS

We found no significant between-group differences in the risk of pregnancy loss, high-level

neonatal care, or overall maternal complications, although less-tight control was associated with

a significantly higher frequency of severe maternal hypertension.

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Efficacy of a Device to Narrow the Coronary Sinus in Refractory

Angina Stefan Verheye, M.D., Ph.D., et al. N Engl J Med 2015; 372:519-527.

BACKGROUND

Many patients with coronary artery disease who are not candidates for revascularization have

refractory angina despite standard medical therapy. The balloon-expandable, stainless steel,

hourglass-shaped, coronary-sinus reducing device creates a focal narrowing and increases

pressure in the coronary sinus, thus redistributing blood into ischemic myocardium.

METHODS

We randomly assigned 104 patients with Canadian Cardiovascular Society (CCS) class III or IV

angina (on a scale from I to IV, with higher classes indicating greater limitations on physical

activity owing to angina) and myocardial ischemia, who were not candidates for

revascularization, to implantation of the device (treatment group) or to a sham procedure (control

group). The primary end point was the proportion of patients with an improvement of at least two

CCS angina classes at 6 months.

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Efficacy of a Device to Narrow the Coronary Sinus in Refractory

Angina Stefan Verheye, M.D., Ph.D., et al. N Engl J Med 2015; 372:519-527.

RESULTS

A total of 35% of the patients in the treatment group (18 of 52 patients), as compared with 15% of those in

the control group (8 of 52), had an improvement of at least two CCS angina classes at 6 months (P=0.02).

The device was also associated with improvement of at least one CCS angina class in 71% of the patients in

the treatment group (37 of 52 patients), as compared with 42% of those in the control group (22 of 52)

(P=0.003). Quality of life as assessed with the use of the Seattle Angina Questionnaire was significantly

improved in the treatment group, as compared with the control group (improvement on a 100-point scale,

17.6 vs. 7.6 points; P=0.03). There were no significant between-group differences in improvement in exercise

time or in the mean change in the wall-motion index as assessed by means of dobutamine echocardiography.

At 6 months, 1 patient in the treatment group had had a myocardial infarction; in the control group, 1 patient

had died and 3 had had a myocardial infarction.

CONCLUSIONS

In this small clinical trial, implantation of the coronary-sinus reducing device was associated with significant

improvement in symptoms and quality of life in patients with refractory angina who were not candidates for

revascularization.

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Association Between Asthma and Risk of Developing Obstructive Sleep Apnea Mihaela Teodorescu, MD, MS, et al. JAMA. 2015;313(2):156-164.

Importance

Obstructive sleep apnea (OSA) is more common among patients with asthma; whether asthma is associated with the

development of OSA is unknown.

Objective

To examine the prospective relationship of asthma with incident OSA.

Design, Setting, and Participants

Population-based prospective epidemiologic study (the Wisconsin Sleep Cohort Study) beginning in 1988. Adult participants

were recruited from a random sample of Wisconsin state employees to attend overnight polysomnography studies at 4-year

intervals. Asthma and covariate information were assessed during polysomnography studies through March 2013. Eligible

participants were identified as free of OSA (apnea-hypopnea index [AHI] of <5 events/h and not treated) by 2 baseline

polysomnography studies. There were 1105 4-year follow-up intervals provided by 547 participants (52% women; mean

[SD] baseline age, 50 [8] years).

Exposures

Questionnaire-assessed presence and duration of self-reported physician-diagnosed asthma.

Main Outcomes and Measures

The associations of presence and duration of asthma with 4-year incidences of both OSA (AHI of ≥5 or positive airway

pressure treatment) and OSA concomitant with habitual daytime sleepiness were estimated using repeated-measures Poisson

regression, adjusting for confounders.

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Association Between Asthma and Risk of Developing Obstructive Sleep Apnea Mihaela Teodorescu, MD, MS, et al. JAMA. 2015;313(2):156-164.

Results

Twenty-two of 81 participants (27% [95% CI, 17%-37%]) with asthma experienced incident

OSA over their first observed 4-year follow-up interval compared with 75 of 466 participants

(16% [95% CI, 13%-19%]) without asthma. Using all 4-year intervals, participants with asthma

experienced 45 cases of incident OSA during 167 4-year intervals (27% [95% CI, 20%-34%])

and participants without asthma experienced 160 cases of incident OSA during 938 4-year

intervals (17% [95% CI, 15%-19%]); the corresponding adjusted relative risk (RR) was 1.39

(95% CI, 1.06-1.82), controlling for sex, age, baseline and change in body mass index, and other

factors. Asthma was also associated with new-onset OSA with habitual sleepiness (RR, 2.72

[95% CI, 1.26-5.89], P = .045). Asthma duration was related to both incident OSA (RR, 1.07 per

5-year increment in asthma duration [95% CI, 1.02-1.13], P = .01) and incident OSA with

habitual sleepiness (RR, 1.18 [95% CI, 1.07-1.31], P = .02).

Conclusions and Relevance

Asthma was associated with an increased risk of new-onset OSA. Studies investigating the

mechanisms underlying this association and the value of periodic OSA evaluation in patients

with asthma are warranted.

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Chlorhexidine Bathing and Health Care-Associated Infections A

Randomized Clinical Trial Michael J. Noto, MD, PhD, et al. JAMA. 2015;313(4):369-378.

Importance

Daily bathing of critically ill patients with the broad-spectrum, topical antimicrobial agent chlorhexidine is

widely performed and may reduce health care–associated infections.

Objective

To determine if daily bathing of critically ill patients with chlorhexidine decreases the incidence of health

care–associated infections.


A pragmatic cluster randomized, crossover study of 9340 patients admitted to 5 adult intensive care units of a

tertiary medical center in Nashville, Tennessee, from July 2012 through July 2013.

Interventions

Units performed once-daily bathing of all patients with disposable cloths impregnated with 2% chlorhexidine

or nonantimicrobial cloths as a control. Bathing treatments were performed for a 10-week period followed by

a 2-week washout period during which patients were bathed with nonantimicrobial disposable cloths, before

crossover to the alternate bathing treatment for 10 weeks. Each unit crossed over between bathing

assignments 3 times during the study.

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Chlorhexidine Bathing and Health Care-Associated Infections A Randomized

Clinical Trial

Michael J. Noto, MD, PhD, et al. JAMA. 2015;313(4):369-378.


The primary prespecified outcome was a composite of central line-associated bloodstream infections (CLABSIs), catheter-

associated urinary tract infections (CAUTIs), ventilator-associated pneumonia (VAP), and Clostridium difficile infections.

Secondary outcomes included rates of clinical cultures that tested positive for multidrug-resistant organisms, blood culture

contamination, health care-associated bloodstream infections, and rates of the primary outcome by ICU.

Results

During the chlorhexidine bathing period, 55 infections occurred: 4 CLABSI, 21 CAUTI, 17 VAP, and 13 C difficile. During

the control bathing period, 60 infections occurred: 4 CLABSI, 32 CAUTI, 8 VAP, and 16 C difficile. The primary outcome

rate was 2.86 per 1000 patient-days during the chlorhexidine and 2.90 per 1000 patient-days during the control bathing

periods (rate difference, ?0.04; 95% CI, ?1.10 to 1.01; P?=?.95). After adjusting for baseline variables, no difference between

groups in the rate of the primary outcome was detected. Chlorhexidine bathing did not change rates of infection-related

secondary outcomes including hospital-acquired bloodstream infections, blood culture contamination, or clinical cultures

yielding multidrug-resistant organisms. In a prespecified subgroup analysis, no difference in the primary outcome was

detected in any individual intensive care unit.

Conclusion and Relevance

In this pragmatic trial, daily bathing with chlorhexidine did not reduce the incidence of health care–associated infections

including CLABSIs, CAUTIs, VAP, or C difficile. These findings do not support daily bathing of critically ill patients with

chlorhexidine.

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Protocolized Sedation vs Usual Care in Pediatric Patients Mechanically Ventilated

for Acute Respiratory Failure A Randomized Clinical Trial Martha A. Q. Curley, RN, PhD, et al. JAMA. 2015;313(4):379-389.

Importance

Protocolized sedation improves clinical outcomes in critically ill adults, but its effect in children is unknown.

Objective

To determine whether critically ill children managed with a nurse-implemented, goal-directed sedation protocol experience

fewer days of mechanical ventilation than patients receiving usual care.


Cluster randomized trial conducted in 31 US pediatric intensive care units (PICUs). A total of 2449 children (mean age, 4.7

years; range, 2 weeks to 17 years) mechanically ventilated for acute respiratory failure were enrolled in 2009-2013 and

followed up until 72 hours after opioids were discontinued, 28 days, or hospital discharge.

Intervention

Intervention PICUs (17 sites; n?=?1225 patients) used a protocol that included targeted sedation, arousal assessments,

extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites; n?=?1224

patients) managed sedation per usual care.


The primary outcome was duration of mechanical ventilation. Secondary outcomes included time to recovery from acute

respiratory failure, duration of weaning from mechanical ventilation, neurological testing, PICU and hospital lengths of stay,

in-hospital mortality, sedation-related adverse events, measures of sedative exposure (wakefulness, pain, and agitation), and

occurrence of iatrogenic withdrawal.

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Protocolized Sedation vs Usual Care in Pediatric Patients Mechanically Ventilated

for Acute Respiratory Failure A Randomized Clinical Trial Martha A. Q. Curley, RN, PhD, et al. JAMA. 2015;313(4):379-389.

Results

Duration of mechanical ventilation was not different between the 2 groups (intervention: median, 6.5 [IQR, 4.1-11.2]

days; control: median, 6.5 [IQR, 3.7-12.1] days). Sedation-related adverse events including inadequate pain and

sedation management, clinically significant iatrogenic withdrawal, and unplanned endotracheal tube/invasive line

removal were not significantly different between the 2 groups. Intervention patients experienced more postextubation

stridor (7% vs 4%; P?=?.03) and fewer stage 2 or worse immobility-related pressure ulcers (<1% vs 2%; P?=?.001).

In exploratory analyses, intervention patients had fewer days of opioid administration (median, 9 [IQR, 5-15] days vs

10 [IQR, 4-21] days; P?=?.01), were exposed to fewer sedative classes (median, 2 [IQR, 2-3] classes vs 3 [IQR, 2-4]

classes; P?<?.001), and were more often awake and calm while intubated (median, 86% [IQR, 67%-100%] of days

vs 75% [IQR, 50%-100%] of days; P?=?.004) than control patients, respectively; however, intervention patients had

more days with any report of a pain score ¡Ý4 (median, 50% [IQR, 27%-67%] of days vs 23% [IQR, 0%-46%] of

days; P?<?.001) and any report of agitation (median, 60% [IQR, 33%-80%] vs 40% [IQR, 13%-67%]; P?=?.003),

respectively.


Among children undergoing mechanical ventilation for acute respiratory failure, the use of a sedation protocol

compared with usual care did not reduce the duration of mechanical ventilation. Exploratory analyses of secondary

outcomes suggest a complex relationship among wakefulness, pain, and agitation.

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Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and

Mortality in Patients With Severe Trauma The PROPPR Randomized Clinical Trial John B. Holcomb, MD, et al. JAMA. 2015;313(5):471-482.

Importance

Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher

blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated

with improved outcomes; however, there have been no large multicenter clinical trials.

Objective

To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma,

platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio.


Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma

centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and

December 2013.

Interventions

Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local

standard-of-care interventions (uncontrolled).


Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis,

blood product volumes transfused, complications, incidence of surgical procedures, and functional status.

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Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and

Mortality in Patients With Severe Trauma The PROPPR Randomized Clinical Trial John B. Holcomb, MD, et al. JAMA. 2015;313(5):471-482.

Results

No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2

group; difference, ?4.2% [95% CI, ?9.6% to 1.1%]; P?=?.12) or at 30 days (22.4% vs 26.1%, respectively;

difference, ?3.7% [95% CI, ?10.2% to 2.7%]; P?=?.26). Exsanguination, which was the predominant cause of

death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group;

difference, ?5.4% [95% CI, ?10.4% to ?0.5%]; P?=?.03). More patients in the 1:1:1 group achieved

hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P?=?.006). Despite the 1:1:1 group receiving

more plasma (median of 7 U vs 5 U, P?<?.001) and platelets (12 U vs 6 U, P?<?.001) and similar amounts of

red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23

prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous

thromboembolism, sepsis, and transfusion-related complications.


Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red

blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at

24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer

experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and

platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.

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ST-segment elevation myocardial infarction in China from 2001 to 2011 (the China

PEACE-Retrospective Acute Myocardial Infarction Study): a retrospective

analysis of hospital data Jing Li, Xi Li,, et al. Lancet 2015; 385: 441–51.

Background

Despite the importance of ST-segment elevation myocardial infarction (STEMI) in China, no nationally

representative studies have characterised the clinical profiles, management, and outcomes of this cardiac

event during the past decade. We aimed to assess trends in characteristics, treatment, and outcomes for

patients with STEMI in China between 2001 and 2011.

Methods

In a retrospective analysis of hospital records, we used a two-stage random sampling design to create a

nationally representative sample of patients in China admitted to hospital for STEMI in 3 years (2001, 2006,

and 2011). In the first stage, we used a simple random-sampling procedure stratified by economic–

geographical region to generate a list of participating hospitals. In the second stage we obtained case data for

rates of STEMI, treatments, and baseline characteristics from patients attending each sampled hospital with a

systematic sampling approach. We weighted our fi ndings to estimate nationally representative rates and

assess changes from 2001 to 2011. This study is registered with ClinicalTrials.gov, number NCT01624883.

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ST-segment elevation myocardial infarction in China from 2001 to 2011 (the China

PEACE-Retrospective Acute Myocardial Infarction Study): a retrospective analysis of

hospital data Jing Li, Xi Li,, et al. Lancet 2015; 385: 441–51.

Findings

We sampled 175 hospitals (162 participated in the study) and 18 631 acute myocardial infarction admissions, of which 13

815 were STEMI admissions. 12 264 patients were included in analysis of treatments, procedures, and tests, and 11 986 were

included in analysis of in-hospital outcomes. Between 2001 and 2011, estimated national rates of hospital admission for

STEMI per 100 000 people increased (from 3·5 in 2001, to 7·9 in 2006, to 15·4 in 2011; ptrend<0·0001) and the prevalence

of risk factors—including smoking, hypertension, diabetes, and dyslipidaemia—increased. We noted significant increases in

use of aspirin within 24 h (79·7% [95% CI 77·9–81·5] in 2001 vs 91·2% [90·5–91·8] in 2011, ptrend<0·0001) and lopidogrel

(1·5% [95% CI 1·0–2·1] in 2001 vs 82·1% [81·1–83·0] in 2011, ptrend<0·0001) in patients without documented

contraindications. Despite an increase in the use of primary percutaneous coronary intervention (10·6% [95% CI 8·6–12·6] in

2001 vs 28·1% [26·6–29·7] in 2011, ptrend<0·0001), the proportion of patients who did not receive reperfusion did not

significantly change (45·3% [95% CI 42·1–48·5] in 2001 vs 44·8% [43·1–46·5] in 2011, ptrend=0·69). The median length of

hospital stay decreased from 12 days (IQR 7–18) in 2001 to 10 days (6–14) in 2011 (ptrend<0·0001). Adjusted in-hospital

mortality did not significantly change between 2001 and 2011 (odds ratio 0·82, 95% CI 0·62–1·10, ptrend=0·07).

Interpretation

During the past decade in China, hospital admissions for STEMI have risen; in these patients, comorbidities and the intensity

of testing and treatment have increased. Quality of care has improved for some treatments, but important gaps persist and in-

hospital mortality has not decreased. National efforts are needed to improve the care and outcomes for patients with STEMI

in China.

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