In the News

New oral anticoagulants, risk prediction for atrial fibrillation, and more.


Elevated heart rate at discharge may be associated with death, readmissions in heart failure patients

Heart failure patients with elevated heart rates at hospital discharge may be at higher risk for all-cause and cardiovascular mortality and for 30-day readmission for heart failure and cardiovascular disease, according to a recent study.

Researchers looked at whether heart rate at hospital discharge was associated with mortality at 30 days and 1 year or with outcomes after hospitalization. They used data from the EFFECT-HF trial, a population-based retrospective chart review of patients at least 18 years of age who were admitted to acute care hospitals with heart failure in Ontario, Canada, from 1999 to 2001 and 2004 to 2005.

Patients were included in the current study if they met the modified Framingham heart failure criteria at presentation, if their discharge summary included a primary diagnosis of heart failure, and if they remained in normal sinus rhythm while they were hospitalized. All-cause 30-day and 1-year mortality were the primary outcomes. Secondary outcomes included cardiovascular death and readmission for heart failure, ischemic heart disease and cardiovascular disease. Results were published in the January Circulation: Heart Failure.

Overall, 9,097 patients with heart failure were included in the study, almost half of whom (47.1%) were men. Patients were classified as having discharge heart rates of 40 to 60 beats/min (n=1,333), 61 to 70 beats/min (n=2,170), 71 to 80 beats/min (n=2,631), 81 to 90 beats/min (n=1,700) or greater than 90 beats/min (n=1,263).

Compared with the reference group (61 to 70 beats/min), those with discharge heart rates in the 2 highest categories had significantly increased all-cause 30-day mortality (adjusted odds ratios, 1.59 for 81 to 90 beats/min and 1.56 for >90 beats/min; P=0.003 and 0.007, respectively). Patients in these 2 categories also had a higher risk for cardiovascular death at 30 days (adjusted odds ratios, 1.59 and 1.65, respectively; P=0.017 for both comparisons).

The highest heart rate, over 90 beats/min, was also associated with higher cardiovascular death and all-cause mortality at 1 year (adjusted odds ratios, 1.47 and 1.41; P=0.005 and <0.001, respectively) compared with the reference category of 40 to 60 beats/min. Those in the highest heart rate category also had more 30-day readmissions for heart failure and cardiovascular disease (adjusted hazards ratios, 1.26 and 1.29; P=0.0021 and 0.004, respectively).

The authors noted that their study did not prove causality and that discharge heart rates were determined from a single reading, among other limitations. However, they concluded that higher heart rates at discharge in heart failure patients were associated with higher risk for all-cause and cardiovascular death for 1 year, as well as a higher risk for readmission for heart failure and cardiovascular disease within 30 days.

“Our study suggests that heart rate, an eminently modifiable prognostic marker, merits attention in the transition from hospital to ambulatory care in the community,” the authors wrote. “Future studies are needed to define the beneficial impacts of both pharmacologic and non-pharmacologic heart rate lowering interventions and to determine if target ranges exist to guide therapy.”

New oral anticoagulants better on balance than warfarin, meta-analysis suggests

In patients with atrial fibrillation, the advantages of all 4 new oral anticoagulants over warfarin seem to outweigh the risks, a recent meta-analysis found.

Researchers searched Medline between Jan. 1, 2009, and Nov. 19, 2013, for phase 3 trials of atrial fibrillation patients who were randomized to take new oral anticoagulants (n=42,411) or warfarin (n=29,272). Included trials also reported both safety and efficacy outcomes. The new oral anticoagulants were dabigatran (110 mg and 150 mg), rivaroxaban, apixaban and edoxaban (30 mg and 60 mg). The main outcomes were stroke and systemic embolic events, hemorrhagic stroke, ischemic stroke, myocardial infarction, major bleeding, gastrointestinal bleeding, intracranial hemorrhage, and all-cause death. Results were published online Dec. 4, 2013, by Lancet.

Patients who took the new drugs had 19% fewer strokes or systemic embolic events than those who took warfarin (relative risk [RR], 0.81; 95% CI, 0.73 to 0.91; P<0.0001). This result was due in large part to a reduction in hemorrhagic stroke (RR, 0.49; 95% CI, 0.38 to 0.64; P<0.0001). Patients who took the new oral anticoagulants also had less all-cause mortality (RR, 0.90; 95% CI, 0.85 to 0.95; P=0.0003) and intracranial hemorrhage (RR, 0.48; 95% CI, 0.39 to 0.59; P<0.0001); however, they had greater gastrointestinal bleeding (RR, 1.25; 95% CI, 1.01 to 1.55; P=0.04). Patients on the 2 low-dose new anticoagulant regimens had a better bleeding profile but more ischemic strokes than those taking warfarin, and their overall reduction in stroke or systemic embolic events wasn't significantly different from warfarin (RR, 1.03; 95% CI, 0.84 to 1.27; P=0.75).

This meta-analysis “support(s) the premise that compared with warfarin, new oral anticoagulants, as a class, reduce all-cause mortality by about 10% …,” the authors wrote. The analysis doesn't answer the question of which new drug is best, editorialists noted, suggesting that “ultimately, the drug could be fitted to the patient, or the patient to the drug, dependent on a focus on safety or efficacy, and on other patient factors, such as renal function and drug compliance.”

Researchers in a second study sought to determine the long-term safety and efficacy of edoxaban compared to warfarin in 21,105 patients with moderate- to high-risk atrial fibrillation and followed patients for a median of 2.8 years. They found that both drugs didn't differ significantly in terms of stroke or systemic embolism but that edoxaban was associated with significantly lower rates of major bleeding (3.43% with warfarin vs. 2.75% with high-dose edoxaban and 1.61% with low-dose edoxaban; hazard ratios, 0.80 and 0.47; P<0.001 for both comparisons). Edoxaban patients also had lower mortality from cardiovascular causes (3.17% vs. 2.74% and 2.71%; hazard ratios, 0.86 and 0.85; P=0.01 for both comparisons). The study was published Nov. 28, 2013, by the New England Journal of Medicine.

A third study reported additional results from the ROCKET AF trial (which found that rivaroxaban and warfarin carried similar risks for stroke/systemic embolism and major/nonmajor clinically relevant bleeding). The new analysis focused on factors that placed patients at greater risk for major bleeding, regardless of whether they took rivaroxaban or warfarin. The risk factors were older age, current or prior smoking, male sex, mild anemia, diastolic blood pressure of at least 90 mm Hg, prior gastrointestinal bleeding, and aspirin use at baseline. The study was published online Dec. 4, 2013, by the Journal of the American College of Cardiology.

Compression stockings don't prevent post-thrombotic syndrome in patients with first DVT

Compression stockings didn't prevent post-thrombotic syndrome in patients who experienced a first deep venous thrombosis (DVT), a study found.

In a randomized controlled trial, researchers from multiple centers assigned 806 patients to active elastic compression stockings (30-40 mm Hg) or placebo stockings that looked the same but had less than 5 mm Hg compression at the ankle. All patients had presented with a first symptomatic, proximal deep venous thrombosis (DVT). A patient was excluded if the use of elastic compression stockings (ECS) was contraindicated, if he or she was unable to apply them, if his or her life expectancy was less than 6 months, if he or she couldn't return for follow-up, or he or she received thrombolytic therapy for the DVT. The main outcome was post-thrombotic syndrome (PTS) diagnosed at ≥6 months; secondary outcomes included severity of PTS, recurrent venous thromboembolism, and quality of life. The results were published online Dec. 6 by The Lancet.

The cumulative incidence of PTS during 2-year follow-up was 14.2% in the active ECS group and 12.7% in the placebo group, a nonsignificant difference. In secondary analysis, there were no between-group differences in distribution of PTS severity category, VTE recurrence rate, death, quality of life, or rate of ipsilateral leg ulcers. Median duration of anticoagulation therapy after DVT was similar in the 2 groups, and type of anticoagulation used also didn't differ between groups. Frequency of stocking use was similar between groups, as well.

Study strengths include its large size, multicenter design, 2-year follow-up, and use of 2 measures (Ginsberg and Villalta) to define PTS, the authors noted. Limitations include a loss of 14% of patients to follow-up and the fact that adherence to stockings diminished over follow-up.

The authors noted that the findings in this study differ from previous randomized trials, which showed benefit of stockings after DVT. The past studies were smaller, open label and in single centers, and the control group wore no stockings rather than placebo stockings, they noted.

The results of the current study suggest ECS might not affect the natural history of PTS after DVT, but it's still unknown whether compression stockings can improve symptoms of established PTS or acute DVT, the authors wrote.

Risk prediction algorithms for atrial fibrillation patients compared

In patients with atrial fibrillation, several algorithms for predicting the risk of thromboembolism performed similarly, although one (the CHA2DS2-VASc) was more effective at identifying low-risk patients.

Researchers in Minnesota performed a longitudinal community-based cohort study of 2,720 patients with atrial fibrillation who were followed for a mean of 4.4 years. There were 350 thromboembolic events validated in the cohort. Several risk factors were found to be associated with events: age over 75 (odds ratio [OR], 2.08), female sex (OR, 1.45), history of hypertension (OR, 3.07), diabetes (OR, 1.58) and history of heart failure (OR, 1.50).

Using the patients' data, 9 different risk algorithms were compared: Atrial Fibrillation Investigators (AFI), Stroke Prevention in Atrial Fibrillation (SPAF), CHADS2-classical, CHADS2-revised, Framingham, National Institute for Health and Care Excellence (NICE), American College of Cardiology/American Heart Association /European Society of Cardiology (ACC/AHA/ESC), Eighth American College of Chest Physicians (ACCP) and CHA2DS2-VASc. Results were published in Stroke on Dec. 5.

There were no profound differences in the algorithms' accuracy at identifying patients at high risk of thromboembolic events, the researchers concluded. There was poor agreement among the tools in categorization of intermediate- and high-risk patients.

Overall, SPAF, CHADS2-revised and CHADS2-classical were the most accurate. However, the newer algorithms, especially the CHA2DS2-VASc, were the best at identifying low-risk patients. The low-risk cohort identified by CHA2DS2-VASc had the lowest event rate (0.11 per 100 person-years).

Identifying low-risk patients is likely to become increasingly important for clinicians, the authors said. The convenience and reduced risks of oral anticoagulants are encouraging a shift toward initiating anticoagulation for all but the lowest-risk patients, although issues like reversibility and myocardial infarction risk remain. Given that the CHA2DS2-VASc algorithm is simple and performed well in this and other studies, it is well suited for identifying these patients, the authors concluded.

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