In the News

Secondhand smoke exposure, bleeding risk with dabigatran versus warfarin, post-op delirium in older adults, and more.


Most nonsmoking inpatients with CHD aren't asked about secondhand smoke exposure

Only 17% of nonsmoking inpatients with coronary heart disease (CHD) said a clinician asked them during their hospitalization about secondhand smoke exposure, a recent study found.

Researchers interviewed 214 patients with ischemic CHD and no reported tobacco or nicotine replacement use who had been admitted to a Boston academic hospital between May 25, 2010, and Jan. 27, 2011. Patients were medically stable with no cognitive impairment and had been hospitalized for 48 hours or less. They were asked about demographics; secondhand smoke exposure in their home, car, and workplace; home and car rules about smoking; beliefs about the risk of secondhand smoke; and whether a clinician had discussed secondhand smoke risks with them. Researchers also collected saliva samples for an assay of cotinine (a nicotine metabolite with a 16-hour half-life). Results were published as a research letter in the January JAMA Internal Medicine.

Seventeen percent of patients (n=37) said they were asked about secondhand smoke exposure. Ten percent (n=21) were asked if they lived with a smoker, and 1% (n=3) were advised to keep their home or car smoke-free. Twenty-two percent of patients (n=47) reported having been exposed to secondhand smoke in the 30 days before hospital admission; 15.4% (n=33) reported exposure in the 7 days before admission. Fourteen percent of patients (n=29) lived with a smoker. Of the 184 patients who had adequate saliva samples, 8% (n=15) had detectable cotinine (≥0.020 ng/mL). Of 72 samples that were analyzed with a more sensitive test, 40% (n=29) had detectable cotinine (≥0.05 ng/mL).

The study findings point to a clear need to address secondhand smoke exposure among nonsmokers hospitalized with cardiac conditions, the authors said. Past research indicates that such exposure in acute coronary syndrome patients is associated with a greater likelihood of subsequent mortality, they added. “Hospitals and health care systems are missing an opportunity to identify and intervene in this major modifiable cardiovascular risk factor,” they wrote. An invited commenter added that “this is a case in which the electronic health record could make a big difference” by prompting clinicians to ask about secondhand smoke exposure and encouraging counseling.

For more on this study, see our Q&A.

Greater bleeding risk with dabigatran than warfarin in Medicare patients, 2 studies find

Two recent studies of Medicare data added to existing evidence that older dabigatran users with atrial fibrillation have higher bleeding risks than warfarin users.

In the first study, researchers retrospectively analyzed medical and pharmacy claims from a random sample of Medicare patients who were newly diagnosed with atrial fibrillation between Oct.1, 2010 and Oct. 31, 2011. All patients started dabigatran (n=1,302) or warfarin (n=8,102) within 60 days of their diagnosis, and were followed until Dec. 31, 2011, or until they discontinued anticoagulant use, switched drugs, or died. Results were published in the January JAMA Internal Medicine.

For any bleeding event, dabigatran was associated with a higher bleeding risk than warfarin after adjustment for patient characteristics (hazard ratio [HR], 1.30; 95% CI, 1.20 to 1.41); it was also associated with greater risk for gastrointestinal (GI) bleeding (HR, 1.85; 95% CI, 1.64 to 2.07) and major bleeding (incidence, 9% vs. 5.9%; HR, 1.58; 95% CI, 1.36 to 1.83). In subgroup analysis of high-risk patients, major and GI bleeding risk remained higher for dabigatran users in the following groups: African-Americans, patients with chronic kidney disease, older patients (≥75 years), and patients with at least 7 comorbidities. Major bleeding risk in dabigatran users was especially high in the first 2 subgroups. However, intracranial hemorrhage risk was lower among dabigatran users compared to warfarin users (HR, 0.32; 95% CI, 0.20 to 0.50).

An editorialist remarked that the study highlights the importance of gathering postmarketing data on drugs recently approved by the FDA, in order to learn about “risks associated with real-world use. [The study authors] give us cause for concern because it appears that the bleeding risk for dabigatran is higher than for warfarin, and significantly greater than originally appeared at the time of FDA approval,” she wrote.

The study authors noted the FDA's investigation of dabigatran didn't adjust for differences in patient characteristics between treatment groups. “Dabigatran and warfarin users are very different in several factors that directly affect the risk of bleeding, and failing to adjust would bias the results, as our unadjusted estimates indicate,” they wrote. Physicians should use caution in prescribing dabigatran, especially to African-Americans and those with renal impairment, they wrote, and should counsel dabigatran patients in how to detect potential GI bleeding. Dabigatran may make the most sense for patients at high risk of intracranial bleeding, they added.

A second study of 134,414 Medicare patients (age ≥65 years) with nonvalvular atrial fibrillation also found elevated risk of GI bleeding, and lower risk of intracranial hemorrhage, in dabigatran users compared to warfarin users. Researchers analyzed claims data on patients who first began taking either dabigatran (n=67,494) or warfarin (n=273,920) between October 2010 and December 2012. Results were published in the Jan. 13 Circulation.

Patients taking dabigatran, either 150 mg or 75 mg twice daily, had more GI bleeding (HR, 1.28; 95% CI, 1.14 to 1.44), fewer intracranial hemorrhages (HR, 0.34; 95% CI, 0.26 to 0.46), fewer ischemic strokes (HR, 0.80; 95% CI, 0.67 to 0.96); and fewer deaths (HR,0.86; 95% CI, 0.77 to 0.96) than those taking warfarin. There were fewer acute myocardial infarctions (HR, 0.92; 95% CI, 0.78 to 1.08) in the dabigatran group, but this finding was not statistically significant. A subgroup of 75-mg, twice-daily dabigatran users had no differences in risk compared to warfarin users, except for lower intracranial hemorrhage risk. Most people who took the lower dabigatran dose “appeared not to have severe renal impairment, the intended population for this dose,” the researchers noted. The subgroup of patients who took the higher dabigatran dose had a greater magnitude of effect for each outcome compared to the combined-dose group of dabigatran users.

Subgroup analyses found that the higher GI bleeding risk with dabigatran occurred in women age 75 years or older and men age 85 years or older; below these thresholds, the GI bleeding risks of dabigatran and warfarin were comparable. Also, there was increased mortality in women age 85 and older with dabigatran compared with warfarin.

“The benefit-risk profile of dabigatran may be less favorable in women age 85 years and older than in other age-gender groups,” the researchers wrote. The results also suggest many patients were treated with the 75-mg dose off label, meaning they may have been under-dosed which “could explain why we found no difference in ischemic stroke, major gastrointestinal bleeding, or mortality between warfarin and the lower dose of dabigatran,” the researchers wrote.

Guideline released on post-op delirium in older adults

The American Geriatrics Society recently released a clinical practice guideline on postoperative delirium in older adults.

The guideline, which was based on a systematic review of the literature and developed by an expert panel, addresses prevention and treatment of delirium after surgery in adults 65 years of age and older, focusing on perioperative nonpharmacologic and pharmacologic interventions.

Strong recommendations included the following:

  • After an older adult has been diagnosed with postoperative delirium, the health care professional should perform a medical evaluation, make medication and/or environmental adjustments, and order appropriate diagnostic tests and clinical consultations to identify and manage underlying contributors to delirium.
  • Health care professionals should optimize postoperative pain control, preferably with nonopioid pain medications, to minimize pain in older adults to prevent delirium.
  • The prescribing practitioner should avoid medications that induce delirium postoperatively in older adults to prevent delirium.
  • In older adults not currently taking cholinesterase inhibitors, the prescribing practitioner should not newly prescribe cholinesterase inhibitors perioperatively to older adults to prevent or treat delirium.

The guideline strongly recommended against using benzodiazepines as first-line treatment of agitated postoperative delirious patients who are threatening substantial harm to themselves and/or others, except when benzodiazepines are specifically indicated. This includes but is not limited to treatment of alcohol or benzodiazepine withdrawal, the guideline said.

Treatment with benzodiazepines should be at the lowest effective dose for the shortest possible duration and should be initiated only if behavioral measures have failed or cannot be used. Ongoing use should be evaluated daily with in-person examination of the patient, the guideline said. In addition, it said, antipsychotic or benzodiazepine medications should not be prescribed to treat older adults with postoperative delirium who are not agitated and threatening substantial harm to themselves or others.

The guideline also recommended that health care systems and hospitals implement multicomponent nonpharmacologic intervention programs delivered by an interdisciplinary team for the entire hospitalization in at-risk older adults undergoing surgery to prevent delirium, as well as implement formal educational programs on delirium for health care professionals, with ongoing formal and/or informal refresher sessions.

The full guideline was published by the American Geriatrics Society on Nov. 18, 2014.

Acute ischemia on CT after TIA predicts subsequent stroke

CT scan results of patients who have recently had a transient ischemic attack (TIA) or nondisabling stroke can help predict their risk of subsequent stroke, a recent study found.

The prospective cohort study included 2,028 patients who received a CT scan within 24 hours of a TIA or nondisabling stroke. The primary outcome of the study was subsequent stroke within 90 days and the secondary outcomes were subsequent stroke within 2 days and subsequent stroke after 2 days. Results appeared in the January Stroke.

Within 90 days of the initial event, 3.4% of the patients had a stroke; 1.5% of all patients had a stroke within 2 days of the event. On CT, 814 of the patients (40.1%) had ischemic changes. Ninety-day stroke risk was increased if the CT showed acute ischemia, and it increased even more if other ischemic changes were present in addition: stroke risk with acute ischemia alone, 10.6% (odds ratio [OR], 2.61); acute and chronic ischemia, 17.4% (OR, 5.35); acute ischemia and microangiopathy, 17.6% (OR, 4.90); acute and chronic ischemia and microangiopathy, 25.0% (OR, 8.04). Risk of stroke within 2 days was increased with acute and chronic ischemia (OR, 10.78), acute ischemia and microangiopathy (OR, 8.90), and acute and chronic ischemia and microangiopathy (OR, 23.66).

The results show that ischemic changes on CT after diagnosis of TIA are associated with increased risk of subsequent stroke, the study authors concluded. Because the association is independent of other factors, CT findings could add power to the data already used to predict stroke risk. The study also shows that patients with nondisabling stroke, rather those with TIA, represent most of the risk of early subsequent stroke.

The creation of a new ABCD2I score, which would add 3 points for evidence of infarction on CT or diffusion-weighted imaging to the existing ABCD2 score, has already been proposed, the researchers noted. These findings support the addition of imaging results to the score but also suggest that allocating points specifically for acute ischemia might be helpful. The study shows that patients with high risk of subsequent stroke after TIA can be identified using CT, rather than requiring the MRI scans used for such patients in large academic centers, the study authors said.

Bridging afib patients whose anticoagulation is interrupted may raise risk of bleeding, adverse events

Routinely bridging patients with atrial fibrillation whose oral anticoagulation is interrupted for a procedure may increase their risk for bleeding and adverse events, an observational study found.

Researchers used a national, community-based registry of 7,372 outpatients with atrial fibrillation (AF) who were taking oral anticoagulation to examine the effects of bridging. Using mostly medical records, they recorded information on temporary interruptions of oral anticoagulation for procedures, including the use and type of bridging therapy, and the type of procedure. Median follow-up was 24 months. Outcomes included multivariable-adjusted rates of myocardial infarction (MI), stroke or systemic embolism (SSE), major bleeding, cause-specific hospitalization, and death within 30 days of bridging. Results were published in the Feb. 3 Circulation.

Thirty percent of patients (n=2,200) had 2,803 interruption events over a period of 2 years. Bridging anticoagulants were used in 24% (n=665) of interruptions, mostly with low-molecular weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had previous cardiovascular events (22% vs. 15%; P=0.0003) and mechanical valve replacements (9.6% vs. 2.4%; P<0.0001), but there was no difference between groups in CHA2DS2-VASc scores. Bridged patients had more bleeding events than non-bridged patients (5.0% vs. 1.3%; adjusted odds ratio [OR], 3.84; P<0.0001); they also were more likely to have MI, SSE, bleeding, hospitalization, or death within 30 days (composite outcome, 13% vs. 6.3%; adjusted OR, 1.94; P=0.0001).

The procedure for which the patient required interruption had minimal influence on composite adverse outcomes, but adverse events were significantly less common for dental procedures. The patient's baseline anticoagulant (warfarin vs. dabigatran) wasn't associated with outcome after temporary interruption. The authors concluded that while nearly a quarter of patients with anticoagulation interruptions receive bridging anticoagulation, the current data do not support the practice.

Editorialists noted that the findings “fly somewhat in the face of conventional dogma and may begin a paradigm shift away from the routine use of bridging strategy for AF patients undergoing procedures.” They said, however, that the results of the secondary analyses showing similar rates of adverse events across procedure types should be interpreted with caution, as this analysis wasn't adequately powered. “We suggest that providers should, until data from larger samples are available, continue to utilize the 3-tier risk stratification system proposed by [the American College of Chest Physicians], which includes procedure type and duration as important contributors to peri-procedural bleeding risk,” they wrote. Two large randomized, placebo-controlled trials are currently underway that should help further inform periprocedural anticoagulation decisions, they noted.

Patients on tramadol more likely to be hospitalized for hypoglycemia

Patients who began taking tramadol were significantly more likely to be hospitalized for hypoglycemia than those prescribed codeine, a recent study found.

The observational case-control analysis used data from the United Kingdom Clinical Practice Research Datalink to find patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012. Hospitalized patients were matched with up to 10 controls on age, sex, and duration of follow up, and then study results were further confirmed by a case-crossover analysis. Results were published in the February JAMA Internal Medicine.

The study found 1,105 patients hospitalized for hypoglycemia during the follow up (0.7 cases per 1,000 patients per year in the cohort of more than 300,000 patients) and they were matched to 11,019 controls. Compared to those who took codeine, patients taking tramadol had a significantly higher risk of hospitalization for hypoglycemia (odds ratio [OR], 1.52; 95% CI, 1.09-2.10). It was particularly high in the first 30 days of use (OR, 2.61; 95% CI, 1.61-4.23), a finding that was confirmed by the cohort (hazard ratio [HR], 3.60) and case-crossover analyses (HR, 3.80).

Tramadol use is significantly associated with hypoglycemia severe enough to require hospitalization, even among patients not taking any antidiabetic drugs, the study authors concluded, noting that such a connection had been previously suggested by case reports. There are biologically plausible explanations for this association and additional investigation is needed into this potentially fatal, although rare, side effect of the drug, they said.

Tramadol has been widely assumed to be safer than other opioid medications, noted an accompanying editorial. However, research has shown it to be abused similarly to other opioids and to carry risks of seizures, serotonin syndrome, and drug interactions, the editorialists wrote. This new finding of a hypoglycemia risk should cause clinicians to be vigilant for this complication and to consider the risks of prescribing tramadol, which may be less predictable than the risks of conventional full opioid agonists.

Guideline issued on platelet transfusions in adults

The AABB (formerly the American Association of Blood Banks) recently released new guidelines on appropriate use of platelet transfusions in adults.

The guidelines, which were developed by an expert panel, are based on a systematic review of the literature that included randomized clinical trials and observational studies in patients receiving prophylactic or therapeutic platelet transfusions. Clinical outcomes examined were all-cause mortality, bleeding-related mortality, bleeding, and number of platelet units transfused. Seventeen randomized, controlled trials and 53 observational studies were included in the final systematic review. While the guideline aimed to establish a platelet count threshold that suggested benefit with transfusion for several common clinical situations, the panel stressed that clinical judgment remains paramount.

The panel's recommendations are as follows:

  • Platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one-half of a standard apheresis unit are equally effective (Grade: strong recommendation; moderate-quality evidence).
  • Prophylactic platelet transfusion is suggested for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L (Grade: weak recommendation; low-quality evidence).
  • Prophylactic platelet transfusion is suggested for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L and for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L (Grade: weak recommendation; very low-quality evidence).
  • The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass (CPB). Platelet transfusion is suggested for patients having CPB who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction (Grade: weak recommendation; very low-quality evidence).
  • The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous) (Grade: uncertain recommendation; very low-quality evidence).

The full guideline was published on Nov. 11, 2014, by Annals of Internal Medicine.

Discharges to post-acute care facilities rose nearly 50% in 15 years

Discharges to post-acute care (PAC) facilities increased 49% between 1996 and 2010, while discharges to home decreased 5% in this time period, a recent study found.

Researchers used the National Hospital Discharge Survey to examine data from 2.99 million sample patient discharges in 50 states between 1996 and 2010. They excluded patients who were transferred to other hospitals, were discharged without a destination code, or had lengths of stay longer than 31 days. Discharge destination and length-of-stay trends were evaluated using 1996 rates as a baseline and were age-adjusted to reflect the U.S. Census age distribution in 2003 (the midpoint of the analysis). Results were published in the February JAMA Internal Medicine.

The proportion of discharges to PAC facilities increased to 13.7% in 2010 from 9.2% in 1996, a 49% relative increase, while the proportion of discharges to home fell to 86.3% in 2010 from 90.8% in 1996, a 5% decrease. The mean length of stay during the study period declined, to 7.8 days in 2010 from 8.8 days in 1996 for those discharged to PAC facilities and to 4.1 days in 2010 from 4.6 days in 1996 for patients discharged to home. The 15-year rise in the discharge rate to PAC facilities corresponds to an adjusted increase of 1.2 million discharges.

The increased discharges to PAC facilities may be an unintended consequence of Medicare's 30-day readmissions penalties, which apply to readmissions from the community but not PACs, and of changes to the payment structure between 1996 and 2010 that reward shorter stays, the authors noted. “The rise in hospitalist care and changes in the epidemiology of diseases admitted to the hospital may also be significant contributors,” they wrote. “Policymakers must consider whether the increase in discharges to PAC facilities represents a positive phenomenon or unintended consequences of payment reform.” Either way, high-quality care transitions to PAC facilities from hospitals are now more important than ever, they wrote.