Recent Research

Thrombolytic therapy and acute PE, bleeding risk in patients on warfarin before MI, and more.


Thrombolytic therapy appears to reduce case fatality in acute PE

Thrombolytic therapy appears to improve case-fatality rates in unstable patients with acute pulmonary embolism (PE), a recent study indicates.

Two researchers used data from the Nationwide Inpatient Sample between 1999 and 2008 to determine whether thrombolytic therapy helps to reduce the case-fatality rate in acute PE. The study examined in-hospital all-cause case-fatality rates by use of thrombolytic therapy in patients with acute PE who were considered medically unstable due to shock or ventilator dependency. Patients were considered to have died of PE if they had a primary diagnosis of PE but did not have any of the comorbid conditions included in the Charlson comorbidity index. The study results were published in the May American Journal of Medicine.

The researchers identified 72,230 unstable patients with PE, of whom 21,390 (30%) were given thrombolytic therapy. The in-hospital all-cause case-fatality rate was 15% in patients who received the therapy versus 47% in those who didn't (P<0.0001). A total of 6,630 patients received thrombolytic therapy and a vena cava filter, while 12,850 patients received a vena cava filter alone; the all-cause case-fatality rate was significantly lower in the former group (7.6% vs. 33%; P<0.0001). When the researchers looked at case-fatality rates due to PE only, they found lower rates in patients who received thrombolytic therapy compared with those who did not (8.4% vs. 42%; P<0.001) and in patients who received both thrombolytic therapy and a vena cava filter compared with those who received only a filter (2.7% vs. 27%; P<0.0001). A linear decrease in thrombolytic therapy use was observed over the study period, from 40% in 1999 to 23% in 2008.

Based on their results, the researchers concluded that thrombolytic therapy appeared to improve both in-hospital all-cause case-fatality rates and case-fatality rates due to PE in medically unstable patients with acute PE. Case-fatality rates were further improved by using a vena cava filter in conjunction with thrombolytic therapy. The researchers noted that only 30% of unstable patients in this study received thrombolytic therapy despite its apparent effectiveness and that use of this therapy appeared to decrease over the study period. “Thrombolytic therapy in combination with a vena cava filter in unstable patients with acute pulmonary embolism seems indicated,” they wrote.

Bleeding risks assessed for patients on warfarin before MI

Many patients who are on home warfarin do not receive guideline-recommended treatment when they have a non-ST-segment elevation myocardial infarction (NSTEMI), a recent study found.

Current guidelines from the American College of Cardiology and American Heart Association suggest holding anticoagulants and initiating antiplatelet therapy when these patients are hospitalized (although the guidelines do acknowledge the need for clinical judgment). Researchers reviewed a Get With The Guidelines registry of more than 5,000 NSTEMI patients who had been on home warfarin to assess treatment patterns and bleeding risks. The results were published in the March 20 Circulation.

Overall, the study found that at hospital admission, 46% of patients had subtherapeutic international normalized ratios (INR <2), 35% had therapeutic levels (INR 2 to 3), and 19% had supratherapeutic levels (INR >3). The risk of major bleeding during hospitalization was significantly higher in patients with higher INR levels: 12% in the subtherapeutic group, 15% in the therapeutic group and 22% in the supratherapeutic group.

When the researchers looked at anticoagulant treatment, they found that 45% of patients with an INR of at least 2 were treated with heparin within 24 hours, despite guidelines to the contrary. These patients less frequently received the recommended early antiplatelet therapy: 35% got clopidogrel and only 14% got early glycoprotein IIb/IIIa inhibitors (GPIs). Slightly more than a third of them (36%) received early invasive management, despite guidelines recommending this for high-risk patients.

All patients who received early antithrombotic treatment were at significantly increased risk of bleeding, regardless of their admission INR (heparin odds ratio [OR], 1.40; clopidogrel OR, 1.50; GPI OR, 1.82). An early invasive strategy was not significantly associated with bleeding, however (OR, 1.09). The researchers said that this last finding could be affected by selection bias in favor of using the early invasive strategy in lower-risk patients. The study authors noted that the current guidelines in this area are based on expert consensus. They called for clinical trials to more precisely guide treatment and help physicians balance prevention of adverse ischemic events with bleeding risk.

Prophylactic haloperidol lowers incidence of postop delirium for some patients

Prophylactic haloperidol reduced the incidence of postoperative delirium in elderly patients admitted to the intensive care unit (ICU) after noncardiac surgery, a study found.

Chinese researchers randomized ICU patients age 65 years or older to either placebo saline (n=228) or a 0.5-mg intravenous bolus injection of haloperidol followed by continuous infusion at a rate of 0.1 mg/hour (n=229). Medication and placebo were started within one hour after enrollment and continued for 12 hours. Patients, who were blinded to treatment, were drawn from two large teaching hospitals in Beijing between June 2009 and May 2010. The primary end point was incidence of delirium in the first seven days after surgery, and secondary end points included safety and tolerance of haloperidol, time to onset of delirium, daily prevalence of delirium, number of delirium-free days, and use of open-label haloperidol. Delirium was assessed using the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). Results were published in the March Critical Care Medicine.

Incidence of delirium in the first seven days after surgery was 15.3% in the haloperidol group and 23.2% in the control group (P=0.031). The mean time to delirium onset was longer in the haloperidol group at 6.2 days versus 5.7 days in the placebo group (P=0.021), as was the mean number of delirium-free days (6.8 days vs. 6.7 days; P=0.027). The median length of ICU stay was shorter in the treatment group, as well (21.3 hours vs. 23.0 hours; P=0.024). There was no significant difference in 28-day all-cause mortality between the groups, and no drug-related side effects were observed.

While there is concern that prophylactic haloperidol can cause side effects like hypotension and sedation, the authors kept the total daily dose below 2 mg to help reduce the risk. Overall, the results indicate prophylactic haloperidol can reduce the incidence of delirium in the week after noncardiac surgery for elderly ICU patients, as well as delay the onset of delirium, they concluded.

Haloperidol has highest mortality risk of several antipsychotics in elderly users

In nursing home patients age 65 years and older, haloperidol is associated with the highest mortality risk out of several antipsychotic drugs, a recent study found.

Researchers analyzed a linked dataset of Medicare and Medicaid claims, the minimum data set (MDS), the Online Survey Certification and Reporting (OSCAR) system and the National Death Index in 45 U.S. states for 2001-2005. The 74,445 patients were age 65 years or older, were dually eligible for Medicare/Medicaid, had started treatment with an antipsychotic during a nursing home stay, and had six months' continuous Medicaid coverage before they started the antipsychotic. The drugs in the study included haloperidol, aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone. Researchers used Cox proportional hazards models to compare 180-day risks of all-cause and cause-specific mortality by individual drug, and they adjusted for potential confounders.

Compared with risperidone—the reference drug—users of haloperidol had a higher mortality risk (hazard ratio [HR], 2.07) while users of quetiapine had a decreased risk (HR, 0.81). These effects were strongest after the start of treatment and stayed after dose adjustment. There were no clinically meaningful differences for other drugs, nor was there evidence that the treatment effect differed for patients with dementia or behavioral disturbances. Mortality risk increased with dosage for all drugs except quetiapine. Results appeared Feb. 23 in BMJ.

The study emphasizes the risks of using antipsychotics and the need to try other means of dealing with behavioral problems in elderly patients with dementia, the authors wrote. If the drugs must be used, clinicians should endeavor to prescribe the lowest possible dose and closely monitor patients, especially right after the start of treatment, they said. Further, this study and previous research “implies the use of haloperidol in this vulnerable population cannot be justified because of the excess harm,” they wrote.

Intervention improved venous thromboembolism prophylaxis

A multi-faceted intervention increased venous thromboembolism (VTE) prophylaxis among medical and surgical patients in an Australian hospital, a recent study reported.

In 2008, a regional referral center in Australia introduced a modification to the Australian National Inpatient Medication Chart (NIMC). The NIMC, a paper-based document, was modified to include a VTE risk stratification and appropriate prophylaxis guidance tool, a prophylaxis contraindication screening instrument, and a prophylaxis prescription prompt. In this retrospective study, researchers tried to assess what effect the modification had on use of VTE prophylaxis. A hospital-wide educational forum was also held at the launch of the intervention.

A year after the launch, prophylaxis use had increased from 52.7% to 66.5% in medical patients and from 77.5% to 89.1% in surgical patients (P<0.001). Prophylaxis use peaked shortly after the intervention but was still significantly improved 12 months out. Adherence rates to prophylaxis guidelines increased from 55.6% before the intervention to 71.0% in medical patients and from 53.6% to 75.6% in surgical patients (P<0.01). The study authors also noted that the intervention was well accepted by clinicians and did not lead to excessive use of prophylaxis in low-risk patients, although they did observe some unnecessary use of combined mechanical and chemoprophylaxis, when chemoprophylaxis would have been sufficient.

Despite the increase in use of prophylaxis, the study did not find a significant change in overall VTE incidence. The risk ratio for incidence after the intervention compared to before was 0.88 (95% CI, 0.48 to 1.62). Study authors suggested that this finding, combined with the peaking of effect, could indicate a need for ongoing education and/or audit and feedback cycles. An accompanying comment also suggested that the intervention may have been successful at reducing potentially preventable VTE despite the lack of change in the overall rate. Before the intervention, 40% of patients with VTE had not previously received prophylaxis, while after the intervention, this was true of only 6%.

Both the study authors and the comment author concluded that multi-faceted interventions such as this one could be an inexpensive method for improving inpatient VTE prophylaxis. “It's time we quit talking and ‘just do it!’” the comment concluded. The study and comment appeared in the March Chest.

Different MI presentations between the sexes diminish with age, study finds

Women who have a myocardial infarction (MI) are more likely than men to present without chest pain and have higher mortality than men of the same age group, but the differences faded with age, researchers found in an observational study.

To examine the relationship among sex, symptoms and hospital mortality, researchers conducted an observational study from the National Registry of Myocardial Infarction, an industry-funded registry of more than 1.1 million patients. In the study, 42% of patients were women, and they were significantly older than men at hospital presentation, with a mean age of 73.9 versus 66.5 years (P<0.001).

Researchers recorded the presence of chest pain (defined as any symptom of chest discomfort, sensation or pressure, or tightness) or arm, neck, or jaw pain occurring before coming to the hospital and receiving a diagnosis of MI. Results appeared in the Feb. 22/29 Journal of the American Medical Association.

The percentage of MI patients who presented without chest pain was 35.4% (95% CI, 35.4% to 35.5%) and was significantly higher among women than men (42.0% [95% CI, 41.8% to 42.1%] vs. 30.7% [95% CI, 30.6% to 30.8%]; P<0.001).

Multivariable analyses showed that sex-specific differences in MI presentation without chest discomfort decreased with advancing age. Odds ratios were broken down by age brackets comparing women to men (P<0.001 for trend):

  • younger than age 45 years, 1.30 (95% CI, 1.23 to 1.36);
  • age 45 to 54 years, 1.26 (95% CI, 1.22 to 1.30);
  • age 55 to 64 years, 1.24 (95% CI, 1.21 to 1.27);
  • age 65 to 74 years, 1.13 (95% CI, 1.11 to 1.15); and
  • age 75 years or older, 1.03 (95% CI, 1.02 to 1.04).

In-hospital mortality was 14.6% for women and 10.3% for men. Younger women presenting without chest pain had higher hospital mortality than younger men without chest pain. Again, these sex differences decreased (or even reversed) as patients aged. Odds ratios for mortality comparing women to men were:

  • age younger than 45 years, 1.18 (95% CI, 1.00 to 1.39);
  • age 45 to 54 years, 1.13 (95% CI, 1.02 to 1.26);
  • age 55 to 64 years, 1.02 (95% CI, 0.96 to 1.09);
  • age 65 to 74 years, 0.91 (95% CI, 0.88 to 0.95); and
  • age 75 years or older, 0.81 (95% CI, 0.79 to 0.83).

The three-way interaction (sex, age, and chest pain) on mortality was significant (P<0.001).

Absence of chest pain may be a more important predictor of death in younger women with MI compared with other similarly aged groups, the authors noted. “Younger women who experience MI may have significantly less narrowing of the coronary arteries than older women or men, possibly because of a hypercoagulable state, inflammation, coronary spasm, or plaque erosion vs. rupture,” they wrote. Another possible explanation, as hypothesized by other investigators, is sex differences in cardiovascular risk factors, they added.

Prior hospitalization, nursing home residency predict multidrug-resistant infection in pneumonia

Among inpatients with pneumonia, hospitalization in the previous 90 days and residence in a nursing home were independent predictors of infection with resistant pathogens, a recent study found.

All risk factors for acquisition of multidrug resistant (MDR) bacteria are currently classified within the same category, so researchers sought to define greater or lesser risks. In an observational, prospective study, they evaluated the risk factors of 935 consecutive patients who were hospitalized with pneumonia at a single hospital in Milan, Italy. Patients who had been hospitalized in the previous 15 days were excluded. The recorded risk factors were hospitalization for ≥2 days in the previous 90 days, residence in a nursing home or extended-care facility, home infusion therapy (including antibiotics), home wound care, chronic dialysis within 30 days, having a family member with an MDR pathogen, antimicrobial therapy in the past 90 days, and immunosuppression. Microbiological testing was used to identify resistant bacteria, and logistic regression models were then used to evaluate risk factors associated with the presence of a resistant pathogen and/or with in-hospital death.

Fifty-one percent of patients (n=473) had one or more risk factors on admission for acquiring MDR bacteria. After adjustments for age, sex and comorbidities, hospitalization in the preceding 90 days independently predicted actual infection with a resistant pathogen (odds ratio [OR], 4.87; P=0.001), as did residency in a nursing home or extended care facility (OR, 3.55; P=0.031). Both factors also independently predicted in-hospital death (prior hospitalization OR, 1.63 and P=0.034; nursing home/extended care residency OR, 2.83 and P=0.001).

Researchers computed a score for predicting risk of infection with resistant bacteria, which included comorbidities and factors related to contact with the health care environment. Scores ranged from 0 to 12.5. Patients who scored ≤0.5 on admission had an 8% prevalence of resistant bacteria while those who scored ≥3 had a 38% prevalence (P<0.001). Results were published in the Feb. 15 Clinical Infectious Diseases.

While their scoring tool performed well, the authors cautioned it was not validated in an independent group of patients. Overall, the study results suggest pneumonia patients should be individually evaluated to target antibiotic therapy, the authors wrote. “On the one hand, a more rigorous and invasive microbiological workup could be indicated for those patients in a high-risk class. On the other hand, the administration of appropriate empiric antibiotic therapy could be optimized, thus minimizing the unnecessary use of broad-spectrum antibiotics in patients in the low-risk class,” they wrote. Editorialists agreed the study results help provide a strategy for clinicians “to balance the need to treat infections appropriately while avoiding the overuse of broad-spectrum antibiotics.”

Assessment test for COPD helps determine exacerbation severity, outcomes

The COPD Assessment Test (CAT) is useful for determining severity of chronic obstructive pulmonary disease (COPD) exacerbations and for measuring recovery after exacerbations and pulmonary rehab, according to two recent studies.

In the first study, U.K. researchers assessed whether the CAT, an eight-item questionnaire about COPD symptoms and health status, could reliably score the severity of COPD exacerbations. The study involved 161 patients who completed the CAT between April 2010 and June 2011 while stable, during an exacerbation and during recovery. Patients were also required to complete daily diary cards noting their daily peak expiratory flow rate, the hours they spent outside the home, and increases in respiratory symptoms. To be included in the study, patients had to have a post-bronchodilator FEV1 of 80% of predicted or less and an FEV1/FVC ratio less than 0.7. Patients who had a history of other significant respiratory disease and those who could not complete daily records of their symptoms were excluded. The study was published early online Jan. 26 by the American Journal of Respiratory and Critical Care Medicine.

During the period assessed, patients had a total of 152 exacerbations, in which CAT scores increased from an average of 19.4±6.8 at baseline to 24.1±7.3 during the exacerbation (P<0.001). Patients who had frequent exacerbations had significantly higher CAT scores at baseline than those who did not (19.5±6.6 vs. 16.8±8.0; P=0.025). Increases in CAT score at exacerbation were significantly associated with FEV1 decreases (P=0.032), and median exacerbation recovery time was significantly related to the time elapsed until the CAT score returned to baseline (P=0.012).

The authors concluded that the CAT provided a reliable way to score COPD exacerbation severity and that patients who have frequent exacerbations are likely to have higher CAT scores at baseline. Because the CAT can be completed easily and quickly, they said, it could be used as part of COPD care bundles. This would potentially help patients get quick treatment for exacerbations, improving recovery and decreasing hospitalizations. They called for additional evaluation of the CAT to determine how it can best be integrated into clinical practice.

The second study looked at whether the CAT could determine changes in patients' health during recovery from a COPD exacerbation and after pulmonary rehabilitation. Two cohorts were separately examined, the first involving 67 patients who had received a clinician's diagnosis of an exacerbation between February and April 2009 and the second involving 64 patients with stable COPD beginning pulmonary rehabilitation from July to December 2009. Researchers assessed how well the CAT detected changes in health status during days 1 to 14 of an exacerbation (cohort 1) and during days 1 to 42 of pulmonary rehabilitation (cohort 2) by examining correlations between the CAT and various outcome measures. The study was published early online Jan. 26 by Chest.

The mean improvement in CAT score over 14 days in cohort 1 was −1.4±5.3 (P=0.03). Patients and clinicians defined patients as responding or not responding to treatment, and under both definitions, those in the responding group had a larger change in CAT score (patients' definitions, −2.8±4.6 vs. −0.0±5.6 [P=0.03]; clinicians' definitions, −2.6±4.4 vs. −0.2±5.9 [P=0.08]). In cohort 2, the mean improvement in CAT score for patients undergoing pulmonary rehabilitation was −2.2±5.3 (P=0.002). In comparisons with other measures of COPD health status, a strong correlation was seen between change in CAT score and change in score on the Chronic Respiratory Questionnaire-Self-Administered Standardized form (CRQ-SAS). Correlations were less strong, however, between change in CAT score and the St. George's Respiratory Questionnaire (SGRQ) in cohort 1 and between change in CAT score and 6-minute walk distance in cohort 2.

The authors concluded that the CAT can be used to detect changes in health status after a COPD exacerbation and after pulmonary rehabilitation and is comparable to other, more complicated measures. They noted that the CAT was able to distinguish between patients who did and did not respond to therapy after an exacerbation, indicating that those whose CAT score does not change or worsens at 14 days may need different or additional treatment. In addition, they wrote, the CAT's performance in cohort 2 indicates that it could be used routinely to assess progress after pulmonary rehabilitation instead of other measures that are more time-consuming and more complex.