Recent Research


Study validates bleeding risk score for oral anticoagulation in atrial fibrillation

Researchers recently developed a new biomarker-based bleeding risk score for patients with atrial fibrillation (AF) to help decision making about oral anticoagulation.

The ABC-bleeding score (age, biomarkers, and clinical history) was validated in both an internal and external study and performed better than the currently used HAS-BLED and ORBIT scores, which are based on clinical risk factors. Results of the industry-funded study were published in the June 4 The Lancet.

In combination with age and history of bleeding, 3 biomarkers inform the ABC-bleeding score: growth differentiation factor-15 (GDF-15), cardiac troponin measured with high-sensitivity assays (cTn-hs), and hemoglobin. Researchers also considered the biomarkers cystatin C, epidermal growth factor receptor (eGFR), the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP), and hematocrit while developing the new score but found the strongest predictors to be the selected 5 components, which accounted for about 91.3% of the full model's predictive ability.

Researchers internally validated the score in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, which randomly assigned 18,201 patients with AF and an increased risk of stroke to warfarin or apixaban. External validation came from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, which randomly assigned 18,113 similar patients to dabigatran or warfarin. The primary safety endpoint in both trials was major bleeding.

Using the available plasma samples for biomarker determinations from 14,537 patients in ARISTOTLE and 8,468 from RE-LY, researchers found that the ABC-bleeding score showed better discrimination and utility than both the HAS-BLED and ORBIT scores (C-index of 0.71 for ABC compared with 0.62 for HAS-BLED and 0.68 for ORBIT in the external validation group). The ABC-bleeding score also performed better than the other 2 scores in multiple subgroups, such as patients without a history of bleeding, patients on concomitant antiplatelet or NSAID therapy, and patients assigned to warfarin, apixaban, or dabigatran.

In addition, the new score consistently predicted major bleeding and intracranial hemorrhages more accurately than the HAS-BLED and ORBIT scores, although the study also validated the superiority of ORBIT over HAS-BLED in predicting major bleeding. The ABC-bleeding score should therefore “be useful as decision support regarding oral anticoagulation treatment in patients with atrial fibrillation,” the study authors concluded.

Lower blood pressure target didn't improve outcomes in acute cerebral hemorrhage

Intensive blood-pressure lowering did not improve outcomes in patients with acute cerebral hemorrhage, according to a study that was halted early for futility.

The ATACH-2 trial included 1,000 patients with intracerebral hemorrhage (volume <60 cm3) and a Glasgow Coma Scale score of 5 or more. Their mean age was 61.9 years, 56.2% were Asian, and baseline mean systolic blood pressure was 200.6 mm Hg. Half were assigned to intensive treatment, a systolic target of 110 to 139 mm Hg, and half were assigned to standard treatment, a target of 140 to 179 mm Hg. Intravenous nicardipine was administered within 4.5 hours of symptom onset.

The primary outcome was death or disability 3 months after randomization, and after adjustment, there was no significant difference between groups (38.7% dead or disabled on intensive treatment vs. 37.7% in the standard group; relative risk, 1.04; 95% CI, 0.85 to 1.27). Within 72 hours, serious treatment-related adverse events occurred in 1.6% of the intensive group and 1.2% of the standard treatment group. In the 7 days after treatment, the intensive group did have a significantly higher rate of renal adverse events (9% vs. 4%, P=0.002).

The study was powered to detect a difference in outcomes of 10 percentage points or more, but the interim analysis found only a 1-point difference, leading to the study's discontinuation, the authors said. They noted that outcomes were significantly better than expected in the standard treatment group, which may have made it harder to show a benefit from intensive treatment.

Still, the authors concluded that for patients with intracerebral hemorrhage, targeting a systolic blood pressure of 110 to 139 mm Hg does not provide clinical benefit over a target of 140 to 179 mm Hg. “It is also possible that the blunting of fluctuations in the systolic blood-pressure level in patients with intracerebral hemorrhage and an acute hypertensive response may exert a therapeutic benefit that is independent of the magnitude of lowering the systolic blood-pressure level,” they wrote.

The results should not be generalized to patients with large intracerebral hemorrhage, intracranial pressure elevation, or compromised cerebral perfusion pressure, the authors noted. The study was published by the New England Journal of Medicine on June 8.

Hospital mobility program led to better mobility after discharge, study shows

An in-hospital mobility assistance program prevented loss of community mobility 1 month after discharge, a recent study found.

The 100 participants, who were admitted for medical conditions such as heart failure, were 65 years or older (mean age, 73.9 years; 97% male; 19% black) and were randomized to either the program or usual care. Results were published online on May 31 by JAMA Internal Medicine.

Mobility program participants received support from a trained research assistant, who helped them set daily goals and incrementally progress to full ambulation, as tolerated. To facilitate goal-setting, these patients received diaries, which they could use to document each time they sat up or walked.

Patients in the usual care group also received visits from the research assistant (to control for the daily attention the program participants received) and were provided with diaries, which instead were used to document frequency of visitors. Visits for both cohorts were about 15 to 20 minutes long and occurred up to twice a day, 7 days a week.

Patients reported activities of daily living (ADLs) 2 weeks before admission, at admission, at discharge, and 1 month after hospitalization. To measure community mobility, researchers used imputed estimates of mean University of Alabama at Birmingham Study of Aging Life-Space Assessment (LSA) scores at admission and 1 month after hospitalization.

The groups were similar in their ability to perform ADL (P=0.62) at all time periods, and this ability did not significantly change over time (P=0.77). However, researchers found significant differences (P=0.02) in LSA scores between the mobility group (mean score, 52.6) and the usual care group (mean score, 41.8)

The mobility group had a 1-month post-hospitalization LSA score that was a “clinically significant” 10 points higher than that of the usual care group (P=0.02) after adjustment for baseline admission values and other covariates. The mobility group reported no falls, whereas 2 patients in the usual care group reported a total of 3 falls.

Limitations of the study, the authors noted, include limited generalizability (because the study occurred in a Veterans Affairs hospital with mostly male patients) and the fact that patients did not have dementia or delirium, which may mean that their mobility was higher than what would be seen in a general medicine population.

Next steps should include replicating these findings in larger studies and examining hospital-level outcomes and the potential value of such interventions, an accompanying editorial suggested. “Policymakers will take note if researchers are able to quantify the relative cost-effectiveness of scaling up mobility interventions,” the editorialist wrote. “Likewise, patients and their caregivers will begin to challenge the culture of bedrest and expect, even demand, that their experience of hospitalization be focused on engaging them in active recovery from their illness.”

Late mortality associated with sepsis not explained by pre-existing conditions, study finds

More than 1 in 5 older patients who survive sepsis may die within 2 years, likely as a consequence of their previous sepsis, according to a recent study.

Researchers compared late mortality among 4 groups: patients admitted with sepsis, adults not currently hospitalized, patients admitted with non-sepsis infection, and patients admitted with an acute sterile inflammatory condition. Results were published online on May 17 by The BMJ.

The study cohort included 14,529 Medicare beneficiaries ages 65 and older who participated in a U.S. Health and Retirement Study survey at least once from 1998 through 2008. Researchers placed 960 patients in the sepsis cohort, 1,750 patients in the non-sepsis infection cohort, and 888 patients in the sterile inflammation cohort, matching patients by propensity for sepsis. They also matched non-hospitalized adults to 777 sepsis patients (80.9%), 788 patients with non-sepsis infection (82.0%), and 504 patients with acute sterile inflammation (55.6%).

Of patients who survived for 30 days after being admitted for sepsis, more than 40% died in the next 2 years, and this late mortality was not explained by patient characteristics or pre-existing conditions. Compared to patients not in the hospital, those with sepsis had a 22.1% (95% CI, 17.5% to 26.7%) absolute increase in late mortality, which was defined as death occurring between 31 days and 2 years after admission. For sepsis patients who survived to 1 year, the adjusted odds ratio (OR) of mortality in the subsequent year was 1.6 (95% CI, 1.1 to 2.4) compared to non-hospitalized patients.

Compared to hospitalized patients with non-sepsis infection, patients with sepsis saw a 10.4% (95% CI, 5.4% to 15.4%) absolute increase in late mortality. At 1 year, the adjusted OR of mortality in the sepsis cohort was 1.6 (95% CI, 1.1 to 2.5) compared to the other infected patients, but at 2 years, survival in both cohorts was statistically indistinguishable.

Finally, compared to those in the hospital for sterile inflammation, sepsis patients had a 16.2% (95% CI, 10.2% to 22.2%) absolute increase in late mortality. The higher mortality in sepsis patients remained at 180 days (adjusted OR 2.0; 95% CI, 1.1 to 3.4) and persisted to 1 year (adjusted OR 1.7; 95% CI, 1.0 to 2.9).

An accompanying editorial noted several unanswered questions: “Does this apparent late risk of mortality extend to patients aged under 65? What are the mechanisms? From what do people actually die? Finally, what could be done to ameliorate this excess risk?” Nevertheless, the editorialist suggested that the new information gleaned from this study may be used to educate both patients and clinicians about the downstream effects of sepsis.

The study authors noted limitations of their observational study, such as the possibility of unmeasured confounding and how they used claims-based algorithms to identify the cohorts, which may have led to some misclassification. Additionally, they employed no measure for the severity of inflammation in the sterile inflammation cohort.