In the News

Multivitamins after first heart attack, acetylcysteine for acetaminophen poisoning, and more.


Multivitamins not protective after first heart attack

High doses of multivitamins and minerals didn't protect against secondary cardiovascular events in stable patients who had experienced a myocardial infarction (MI), a recent study found.

Researchers at 134 U.S. and Canadian academic and clinical sites conducted a double-blind, placebo-controlled, 2 ×2 factorial, multicenter, randomized trial of 1,708 patients aged 50 years or older who had had an MI at least 6 weeks earlier and had serum creatinine levels of 2.0 mg/dL (176.8 µmol/L) or less. Patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture (median time of 31 months) or placebo (median time of 35 months) with a primary end point of time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. Results appeared in the Dec. 17, 2013, Annals of Internal Medicine.

The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group, a non-significant difference. The Kaplan-Meier 5-year event rate estimates were 34.2% for the vitamin group and 37.0% for the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.21). The composite of cardiovascular death, MI, or stroke occurred in 94 (11%) patients in the vitamin group and 115 (13%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.62 to 1.07; P=0.142).

Serious adverse events occurred in 124 (15%) vitamin recipients and 103 (12%) placebo recipients (difference, 3 percentage points; 95% CI, −0.7 to 5.7 percentage points). Adverse events included 12 (1.4%) incident neoplasms in the vitamin group and 11 (1.3%) in the placebo group (difference, 0.1 percentage point; 95% CI, −0.8 to 1.3 percentage points). No evidence suggested harm from vitamin therapy in any category of adverse events. Researchers cautioned that a considerable nonadherence and withdrawal rate limited the study's ability to draw firm conclusions, particularly about safety.

Another study in the same issue of Annals found that long-term use of a daily multivitamin did nothing to slow cognitive decline among male physicians 65 and older, while a systematic review in the issue found insufficient evidence that multivitamins prevent cancer, cardiovascular disease or death in otherwise healthy persons without known nutritional deficiencies.

Editorialists responding to the studies urged adults to stop using dietary supplements. Other reviews and guidelines have consistently found null results or possible harms from dietary supplements, they wrote. “The message is simple: Most supplements do not prevent chronic disease or death, their use is not justified, and they should be avoided....,” they wrote. “Although available evidence does not rule out small benefits or harms or large benefits or harms in a small subgroup of the population, we believe that the case is closed….Enough is enough.”

Shorter treatment with acetylcysteine for acetaminophen poisoning may have advantages

Reducing the duration of acetylcysteine treatment for acetaminophen poisoning lowered the occurrence of vomiting and anaphylactoid reactions, a recent study found.

In a double-blind trial at 3 U.K. hospitals, researchers randomized 222 patients with acute acetaminophen overdose to 300 mg/kg intravenous acetylcysteine over the standard duration of 20 to 25 hours or the same dose over 12 hours. Patients were then randomized to receive 4 mg of intravenous ondansetron pretreatment or placebo. The main outcome was absence of vomiting, retching or need for rescue antiemetics at 2 hours. Results were published in the Feb. 22 The Lancet.

Patients with the shorter acetylcysteine treatment duration had less vomiting, retching or rescue antiemetics than those on the standard regimen (adjusted odds ratio [AOR], 0.26; P<0.0001), as did patients who took ondansetron instead of placebo (AOR, 0.41; P<0.003). There were also fewer severe anaphylactoid reactions in shorter-duration acetylcysteine patients (AOR, 0.23; P<0.0001). In analysis of a prespecified secondary outcome, researchers found that the proportion of patients with a 50% increase in alanine aminotransferase activity didn't differ between patients with different durations of acetylcysteine treatment but that ondansetron patients were more likely to have an increase than placebo patients (AOR, 3.30; P=0.024).

In addition to the apparent benefit in terms of vomiting, retching and rescue antiemetics, shorter acetylcysteine treatment “offers simpler administration, a probable reduction in administration errors, and a potential decrease in the length of hospital stay,” the researchers wrote. Still, more trials with a greater number of patients are needed to confirm the safety and efficacy of the shorter regimen before it is adopted widely, they added.

Late transfer of AMI patients from nonprocedure hospitals doesn't improve outcomes

Patients with acute myocardial infarction (AMI) who were transferred after the second day from hospitals that don't do cardiac procedures to those that do didn't fare better at 30 days than patients who weren't transferred, a study found.

Researchers used Medicare claims data from 2006 to 2008 to assess transfer rates in hospitals that lacked on-site cardiac catheterization and coronary revascularization facilities (nonprocedure hospitals). The data comprised 55,962 patients admitted to 901 nonprocedure U.S. hospitals with more than 25 annual admissions for AMI. Most patients were transferred after the second day of admission. Researchers examined catheterization rates, percutaneous coronary intervention (PCI) rates, and coronary artery bypass grafting (CABG) rates during hospitalization and within 60 days. They also examined hospital length of stay and risk-standardized mortality rates at 30 days and 1 year.

The median length of stay was 5 days, and the median transfer rate was 29.4%. The mean 30-day risk-standardized mortality rate was 22.1%. There was no association between transfer rate and length of stay, nor was there a difference in 30-day mortality between low- (22.3%), mid-low- (22.1%), mid-high- (22.3%) and high-transfer (21.7%) groups. At 1 year, there was only a 1.1% difference (42.8% vs. 43.9%) in mortality of patients at hospitals with higher and lower transfer rates, although the former were more likely to receive PCI, CABG or cardiac catheterization within 60 days. Results were published in the February JAMA Internal Medicine.

The findings offered little evidence that hospitals with high transfer rates had better clinical outcomes, the researchers wrote—noting, however, that they didn't examine transfers from the ED. There was great variability in transfer rates among nonprocedure hospitals, the researchers wrote, which suggests “clinical needs have not been a primary driver [of transfers].”

It is possible that transferring AMI patients “is a complex process that depends on other key processes, including the proper selection of patients at the right time, to be translated into a net benefit,” they wrote. Indeed, past research has found that the highest-risk patients aren't the ones most likely to be referred for cardiac catheterization, they noted.

Another reason for the lack of association between transfer rates and mortality rates in this study could be that the hospital transfer rate of 29.4% was too low to register better results for patients, the researchers wrote. Also, they were not able to evaluate the associations according to myocardial infarction subtype, severity of AMI, or physical or cognitive function. In addition, the researchers noted that the efficacy of a more intensive strategy for high-risk patients has not been definitively confirmed outside the setting of ST-elevation myocardial infarction.

Overall, the study suggests that “promoting late transfer of patients admitted with acute myocardial infarction as a single intervention is unlikely to improve hospital outcomes,” they concluded. “The implementation of this strategy may be creating the difference between the expected result and what is being achieved.”

Early antibiotics, combo therapy associated with ICU survival in severe pneumococcal CAP

Early antibiotic administration and use of combination therapy have increased over time in severe pneumococcal community-acquired pneumonia (CAP) and are associated with better outcomes, according to a recent study.

Researchers performed a matched case-control study using 2 European prospective cohort studies, CAPUCI I and CAPUCI II, to determine whether changes in antibiotic prescribing practices over time affected ICU survival in patients with severe pneumococcal CAP caused by Streptococcus pneumoniae. CAPUCI I involved patients admitted to the ICU for CAP at 33 hospitals from 2000 to 2002, while the follow-up study, CAPUCI II, involved patients admitted for severe CAP from 2008 to 2013 in 29 ICUs.

Patients were admitted to the ICU because they needed mechanical ventilation or were critically ill (based on Infectious Diseases Society of America/American Thoracic Society guidelines) and were observed until discharge from the ICU or death. Cases were matched with controls according to shock at admission, need of mechanical ventilation, chronic obstructive pulmonary disease, immunosuppression and age. Study results were published online Dec. 26, 2013, by Chest.

The study included 80 cases from CAPUCI II and 80 matched controls from CAPUCI I. Sixty percent of patients had shock at ICU admission and 65.0% had mechanical ventilation. In addition, 33% of patients were older than 65 years. Overall, between the 2 groups, 66.2% of controls received combined antibiotic therapy compared with 87.5% of cases (P<0.01), and the proportion of patients who received a first dose of antibiotics within 3 hours increased from 27.5% to 70% (P<0.01).

Cases had significantly lower ICU mortality as a whole (17.5% vs. 32.5%; odds ratio, 0.82; 95% CI, 0.68 to 0.98) and in subpopulations with shock (odds ratio, 0.67; 95% CI, 0.50 to 0.89) and those receiving mechanical ventilation (odds ratio, 0.73; 95% CI, 0.55 to 0.96). ICU mortality increased in multivariate analysis among patients who required mechanical ventilation (odds ratio, 5.23; 95% CI, 1.60 to 17.17) but decreased in those who received antibiotics early (odds ratio, 0.36; 95% CI, 0.15 to 0.87) and those who received combination therapy versus monotherapy (odds ratio, 0.19; 95% CI, 0.07 to 0.51).

The authors noted that prescription of antibiotics and hemodynamic resuscitation were not standardized for all patients and that the study could not account for recently introduced improvements in the care of critically ill patients, such as management of septic shock. They also noted that selection bias was a possibility, among other limitations. However, they concluded that in patients with severe pneumococcal CAP, “incidence, mortality and management of severe pneumococcal pneumonia had significantly changed in the last decade” and that earlier antibiotic use and more use of combination therapy were each associated with better survival.

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