Organ failure in ICU predicts five-year survival
Organ failure during critical illness strongly predicts five-year survival, including in patients who live up to a year after ICU admission, a study found.
Researchers undertook a secondary analysis of data from a study involving sequential admissions to ten Scottish ICUs during a 100-day period in 2001. For each of the 872 patients, researchers evaluated the five organ systems (cardiovascular, respiratory, renal, coagulation and liver) daily and determined the Sequential Organ Failure Assessment (SOFA) score ranging from 0 (no dysfunction) to 4 (severe dysfunction). Results were grouped such that a score of 3-4 described organ failure and a score of 0-2 described no organ failure. Total organ failure burden was derived by adding the worst individual organ failure scores at any time point during the ICU stay, with groups defined as mild (0-5), moderate (6-10) and severe (≥11). Researchers used logistic regression analysis to determine independent associations between mortality and organ failures over five years, with adjustment for possible confounders. Results were published in the Oct. 1, 2012 American Journal of Respiratory and Critical Care Medicine.
Higher total burden of organ failure was strongly associated with mortality; patients in the severe category had an 80.7% five-year mortality rate compared to 35% mortality for mild patients (odds ratio [OR], 6.3; P<0.001). Moderate patients had 57.4% mortality at five years. Patients who lived more than 12 months after their ICU stay were still more likely to die if they had had a higher organ failure burden in the ICU (OR, 2.4; P=0.02 for severe vs. mild groups). In the multivariable analysis adjusting for each organ failure and confounders, cardiovascular (OR, 2.5; P<0.001), liver (OR, 2.3; P=0.04) and respiratory failure (OR, 2.1; P=0.004) were associated with higher five-year mortality while coagulation and renal failure were not.
Using a cumulative score of organ failure to measure total organ failure burden yielded a stronger association with long-term mortality than have other existing measures of illness severity, like the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Simplified Acute Physiology Score (SAPS) II, or the daily total SOFA or total SOFA at discharge, the authors noted. It may be that acute organ failure that necessitates ICU admission leads to residual organ damage which lowers survival; or, a high cumulative score may be a marker for those who are likely to develop chronic ICU-acquired morbidities, the authors wrote.
Future studies should gather comprehensive information on comorbidities present before ICU admission as well as those that develop after critical illness, to better tease out any confounding due to pre-existing illness, they advised.
Study clarifies best time for non-cardiac surgery after stents
The ideal earliest time for elective, non-cardiac surgery after bare-metal stent implementation is 46 to 180 days, while for drug-eluting stents it is after 180 days, a recent study found.
Researchers used linked registry data and population-based databases for a retrospective cohort study of 8,116 patients in Ontario, Canada. The patients, age 40 years or older, had undergone major elective surgery between 2003 and 2009, and had received coronary stents within 10 years prior to surgery. About 34% (n=2725) had received stents within two years before surgery; of those patients, 33% (n=905) had received drug-eluting stents. Patients were categorized based on the type of stent implanted and the duration of time between stenting and index surgery. A separate cohort of 341,350 surgical patients without stents was used for comparison. The primary outcome was 30-day major adverse cardiac events (mortality, readmission for acute coronary syndrome or repeat coronary revascularization), though patients were tracked for one year after surgery.
Overall, the rate of 30-day cardiac events in patients with stents was 2.1%; the one-year event rate was 9.8%. When surgery was done less than 45 days after stent insertion, event rates were 6.7% for bare-metal stents and 20% for drug-eluting stents. When surgery was done between 45 and 180 days after stent insertion, the event rate dropped to 2.6% for bare-metal stents, which came close to that of non-stented individuals who had one to two risk factors (intermediate risk) for cardiac events. In adjusted analyses, it appeared that event rates increased again if the surgery occurred more than 180 days post-stent-implantation. For drug-eluting stents, however, the event rate dropped to 1.2% when the time between stent implantation and surgery exceeded 180 days. Results were published in the Sept. 11, 2012 Circulation.
Current practice guidelines recommend that elective non-cardiac surgery be delayed until at least 30 to 45 days after bare-metal-stent implantation, and 365 days after drug-eluting-stent implantation. While the study supports the guidelines about the 45-day waiting period for bare metal stents, it is new in suggesting that the risk may actually rise again 180 days after stent implantation, the authors noted. On the other hand, the study suggests patients can have surgery six months after drug-eluting stents, rather than waiting a whole year, they noted. This study also “confirmed observations of substantially increased risk when surgery is performed within six weeks of coronary stent implantation,” the authors noted.
Measure troponin in elderly after hip fracture surgery, study suggests
Very old patients undergoing hip fracture surgery should have troponin levels measured in the postoperative period, as there is a high incidence of perioperative myocardial infarction (PMI) and the symptoms are usually absent, a study suggests.
In a retrospective case-control study, researchers examined outcomes of 1,212 Minnesota patients (mean age, 85.3 years) who underwent hip fracture surgery from 1988 to 2002. Outcomes were acute myocardial infarction within the first seven days after hip fracture surgery and death from any cause within a year of hip fracture surgery. Creatine kinase-MB fraction was used from 1988 to July 2000 as the biomarker, and troponin was used afterward. For each case of PMI, researchers identified two control patients selected at random from the non-PMI population, matched the cases on age and gender, and compared baseline characteristics. Results were published online Sept. 6, 2012 by the Journal of Hospital Medicine.
Nearly 14% (n=167) of patients had PMI within seven days of surgery; of these incidents, 92% occurred in the first 48 hours. In-hospital mortality was 14.4% in patients with PMI versus 1.2% in non-PMI patients (P<0.001), 30-day mortality was 17.4% versus 4.2% (P<0.001), and one-year mortality was 39.5% versus 23% (P<0.001). Median length of stay was higher among patients who had PMI (11.6 vs. 7.4 days, P<0.001). Of patients with PMI, only 25.2% had symptoms of ischemia; 7% reported chest pain and 12% reported dyspnea. Only 22.8% of PMI patients had electrocardiograph changes consistent with ischemia. “Our study highlights the continued need for active surveillance of clinical symptoms, post-operative ECG monitoring for [ST-segment and T-wave] changes, and utilizing cardiac troponin in older postoperative patients to improve diagnostic accuracy of PMI,” the authors wrote.
A separate retrospective analysis of 95,227 Danish patients found that risk of acute myocardial infarction (AMI) was much higher in the first two weeks after total hip replacement (THR) and total knee replacement (TKR) surgery, compared with controls. For THR patients (mean age, 71.9 years), the risk was 25 times higher, and for TKR patients (mean age, 67.2 years), the risk was 31 times higher. An elevated risk remained for THR patients for two to six weeks after surgery (adjusted hazard ratio, 5.05), while the risk for TKR patients didn't persist beyond the initial two weeks post-surgery. “Risk assessment of AMI should be considered during the first six weeks after THR surgery and during the first two weeks after TKR surgery,” said the authors, who published their results in the Sept. 10, 2012 Archives of Internal Medicine.
Triple antithrombotics carry high bleeding risk for afib patients after MI, PCI
For atrial fibrillation patients who had myocardial infarction (MI) or percutaneous coronary intervention (PCI), triple antithrombotic therapy carries a higher risk of bleeding than other regimens, and should be used cautiously, a recent study suggested.
Using national registries, Danish researchers identified 11,480 patients with atrial fibrillation who were admitted for MI or PCI from 2001 through 2009. Patients were classified into five types of treatments: single antiplatelet therapy with aspirin or clopidogrel; vitamin K antagonist (VKA) monotherapy; dual antiplatelet therapy (DAPT) with aspirin and clopidogrel; VKA plus aspirin or clopidogrel; or triple therapy (TT) with VKA, aspirin and clopidogrel. The primary outcome was non-fatal or fatal bleeding; the combined secondary endpoint was cardiovascular death, non-fatal MI or ischemic stroke. Results were published in the Sept. 4, 2012 Circulation.
Incidence rates of bleeding rose immediately after TT initiation, and TT bleeding rates were higher than for the other regimens regardless of how much time had passed. Within 30 days, crude rates were 22.6, 20.3 and 14.3 major bleeding events per 100 person-years for TT, VKA plus single antiplatelet, and DAPT, respectively. In adjusted analysis, all types of regimens except VKA monotherapy had a higher risk earlier after initiation vs. later. Both early (≤90 days) and delayed (90-360 days) bleeding risk was higher with TT than VKA plus antiplatelet (hazard ratio, 1.47 and 1.36, respectively); there was no significant thromboembolic risk between these two regimens. In long-term follow-up (mean 288 days), the overall trend was that bleeding rates increased while thromboembolic rates decreased with intensity of antithrombotic treatment regimen. In the secondary endpoint, TT performed similarly to VKA plus single antiplatelet therapy in having a favorable effect.
Although the bleeding risk associated with using TT in AF patients after MI or PCI decreased over time, the initial higher risk of TT still was sustained over time compared to less intensive regimens, “indicating no safe therapeutic window of TT in respect to bleeding risk,” the authors wrote, adding “TT should only be prescribed after careful evaluation of bleeding risks.” Clinicians should also be aware of the short-term hazard with VKA plus single antiplatelet “that seems most apparent during the first three months,” they wrote.
Use corticosteroids cautiously in ICU-acquired pneumonia patients
Systemic corticosteroids should be used “very cautiously” in patients with ICU-acquired pneumonia, as the drugs are associated with greater mortality in this population, a study found.
Researchers studied 316 consecutive patients with ICU-acquired pneumonia in an 800-bed hospital from January 2007 to January 2011. Outcomes of patients who received an equivalent dosage of at least 20 mg of systemic methylprednisolone per day in the prior two days—and before development of ICU pneumonia—were compared with those of patients who didn't receive corticosteroids. Researchers calculated the cumulative dosage of corticosteroids received before the onset of pneumonia, expressed as methylprednisolone equivalent dosage. The primary outcome was 28-day survival after diagnosis of ICU-acquired pneumonia, which was analyzed using Cox regression analysis. Patients with severe immunosuppression were excluded from the study. Results were published in the September 2012 Critical Care Medicine.
Forty percent (n=125) of patients were receiving corticosteroids at pneumonia onset. Though clinical severity was similar at baseline, steroids were associated with lower 28-day survival (adjusted hazard ratio, 2.50; P=0.017) and lower systemic inflammatory response. In adjusted analysis, there was a higher risk of death with steroid use among patients with lower baseline organ dysfunction scores (P=0.05), and among those without bacteremia (P=0.03) or acute respiratory distress syndrome (P=0.03). Cumulative steroid dosage didn't have a significant effect on mortality risk, but was associated with increased bacterial burden.
The frequent use of systemic corticosteroids before development of ICU-acquired pneumonia and their associated death risk, as well as the higher bacterial lung burden in patients taking steroids, were the most important findings of the study, the authors noted. The results also confirm that corticosteroids are potentially harmful in less severely ill patients and those at lower risk of death. In part, this may be because “steroid therapy is better able to control the inflammatory response when it is excessive, while increasing the risks in the subgroup with normal or decreased inflammatory response,” they wrote. Thus, systemic corticosteroids should be used “very cautiously,” in this population, they said.
Continuous ECG monitoring beats 24-hour Holter to detect paroxysmal afib after stroke
Continuous electrocardiographic (ECG) monitoring improves detection of paroxysmal atrial fibrillation (pxAF) in patients on stroke units compared with 24-hour Holter ECG, a study found.
Researchers screened consecutive patients with transient ischemic attack (TIA) and ischemic stroke who were admitted to a single stroke unit in a 10-month period ending January 2011. After a 12-lead ECG on admission, all patients received 24-hour Holter ECG and continuous stroke unit ECG monitoring (CEM). ECG monitoring data underwent automated analysis using dedicated software to identify pxAF. Persistent AF was diagnosed in patients without evidence of sinus rhythm in any ECG performed. AF was classified as paroxysmal in all cases in which sinus rhythm and at least one episode of AF, lasting for more than 30 seconds, was documented during hospitalization. Results were published in the October 2012 Stroke.
Of the original 832 patients, 496 fulfilled all criteria for data analysis, which included no previously known AF in medical history and no AF on admission ECG. Eighty percent of patients in the study had ischemic stroke and 20% had TIA. Median stroke unit stay was 88.8 hours. ECG data for automated CEM analysis were available for a median time of 64.0 hours. Paroxysmal AF was documented in 8.3% of patients (n=41). Of these, Holter detected pxAF in 34.1%; CEM found it in 65.9%; and automated CEM in 92.7%. CEM and automated CEM detected significantly more patients with pxAF than Holter (P<0.001), and automated CEM detected significantly more patients than CEM (P<0.001).
The most likely explanation for the superiority of CEM is that it monitored cardiac rhythm for a longer time than 24-hour Holter, the authors noted, “and we cannot exclude that repetitive or prolonged 24-hour Holter recordings may have yielded a comparable rate of pxAF.” Until further studies on prolonged Holter use are available, however, this study suggests continuous ECG monitoring may replace 24-hour Holter ECG as the routine diagnostic procedure for the detection of pxAF on stroke units, they concluded.
Drug may reduce transfusions but increase thrombosis in certain liver disease patients
Eltrombopag, an oral thrombopoietin-receptor agonist, may reduce the need for platelet transfusions in patients with thrombocytopenia and chronic liver disease who are undergoing invasive elective procedures but is associated with an increased incidence of portal-vein thrombosis, according to a recent industry-funded study.
Researchers randomly assigned 292 patients with chronic liver disease and platelet counts below 50,000 mm3 to receive a 14-day course of eltrombopag, 75 mg/d, or placebo before undergoing an elective invasive procedure, which was done within five days of the last drug dose. The study's primary end point was whether platelet transfusions were avoided before, during and up to a week after the procedures. Results of the study, which was funded by GlaxoSmithKline, appeared in the Aug. 23, 2012 New England Journal of Medicine.
One hundred forty-five patients were assigned to the eltrombopag group, and 147 were assigned to the placebo group. The median patient age was 53 years. Overall, 104 patients in the eltrombopag group (72%) and 28 in the placebo group (19%) avoided a platelet transfusion (P<0.001). Bleeding episodes did not differ significantly between the two groups, and rates of most other adverse events were also similar. Portal-vein thrombosis, however, occurred more frequently in the eltrombopag group than in the placebo group (six patients vs. one patient), and the study was terminated early as a result.
The authors concluded that patients with chronic liver disease who received eltrombopag before an elective invasive procedure were less likely to require platelet transfusion but appeared to have an elevated risk of portal-vein thrombosis. They called for further studies of eltrombopag therapy to better identify risk factors for thrombosis, appropriate dose, and appropriate patients, and said until those studies are done, “eltrombopag is not recommended as an alternative to platelet transfusion in patients with chronic liver disease and thrombocytopenia who are undergoing an elective invasive procedure.”
CABG stroke risk higher than PCI
Coronary revascularization by coronary artery bypass graft (CABG) compared with percutaneous coronary intervention (PCI) is associated with an increased risk of stroke, a meta-analysis found.
Researchers performed a meta-analysis of 19 trials in which 10,944 patients were randomized to either procedure. The primary end point was the 30-day rate of stroke. They also determined the rate of stroke at the midterm follow-up and investigated whether there was an interaction between either procedure and the extent of coronary artery disease on the relative risk of stroke.
Results appeared in the Aug. 21, 2012 Journal of the American College of Cardiology.
The 30-day rate of stroke was 1.20% after CABG compared with 0.34% after PCI (odds ratio, 2.94; 95% confidence interval [CI], 1.69 to 5.09; P<0.0001). Similar results were observed after a median follow-up of 12.1 months (1.83% vs. 0.99%; odds ratio, 1.67; 95% CI, 1.09 to 2.56; P=0.02).
The extent of coronary artery disease (single vessel vs. multivessel vs. left main) did not affect the relative increase in the risk of stroke observed with CABG compared with PCI at either 30 days (P=0.57 for interaction) or midterm follow-up (P=0.08 for interaction), the authors noted.
Similar findings were observed when results from 27 studies, including 33,980 patients enrolled in observational studies, were analyzed. Patients treated with CABG had an increased risk of stroke compared with PCI both at 30 days and at a median follow-up of 14.2 months. Patients treated with CABG have an excess of seven strokes for every 1,000 patients treated, the authors concluded.
Kidney disease increases risks of atrial fibrillation
Patients who have both chronic kidney disease and atrial fibrillation are at higher risk of stroke, thromboembolism and bleeding, a recent study found.
Researchers collected data on all patients discharged from Danish hospitals with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. Of the more than 130,000 patients studied, 2.7% had non-end-stage chronic kidney disease and an additional 0.7% was on renal-replacement therapy at the time of hospitalization. The study was published in the New England Journal of Medicine on Aug. 16, 2012.
The kidney disease and atrial fibrillation patients had a significantly increased risk of stroke or systemic thromboembolism compared to those with only atrial fibrillation (hazard ratio for non-end-stage group, 1.49 [95% CI, 1.38 to 1.59]; hazard ratio for renal-replacement group, 1.83 [95% CI, 1.57 to 2.14]). Taking warfarin appeared to reduce this risk (to a similar degree as in non-kidney-disease patients), but aspirin did not. The kidney disease group also had an increased risk of bleeding, which was further increased by aspirin, warfarin, or both.
The risk of stroke and thromboembolism was not affected by the severity of the kidney disease (either non-end-stage chronic kidney disease or renal-replacement therapy), the researchers noted, but the bleeding risk increased for patients with non-end-stage disease with larger doses of loop diuretics. Because warfarin was found both to reduce clot risk and increase bleeding risk, careful assessment is required to determine its likely effects in individual patients with kidney disease, the authors said. A clinical trial should be conducted to more precisely determine the effects of warfarin in these patients.
The authors also called for clinical trials of oral anticoagulants in patients with chronic kidney disease. Thus far, trials of these new drugs have largely excluded patients with kidney disease. The authors cautioned that their conclusions were limited by the observational nature of the trial and the availability of over-the-counter aspirin, among other factors.
IV treprostinil carries higher risk of bloodstream infections than epoprostenol for PAH patients
Pulmonary arterial hypertension (PAH) patients treated with intravenous (IV) treprostinil had a significantly higher rate of gram-negative bloodstream infections (BSI) than those treated with IV epoprostenol, a study found.
Researchers studied the 3,518 patients with PAH enrolled in the REVEAL registry from late March 2006 through early December 2009. REVEAL is a 55-center, observational, U.S.-based longitudinal registry meant to provide demographic, disease course and treatment information about PAH patients. Researchers collected data on reported BSIs through the third quarter of 2010, and calculated BSIs per 1,000 patient-days of risk. Patients were either already receiving an IV prostanoid at enrollment or IV prostanoid therapy was initiated during the study period. Results were published online Aug. 9, 2012 by Mayo Clinic Proceedings.
Of enrolled patients, 1,146 received IV prostanoid therapy for more than one day. Of that subgroup, 1,023 patients had no BSI and 123 patients had a BSI; overall BSI episodes totaled 166. Patients who received IV treprostinil had BSI rates of 0.36 per 1,000 treatment days compared to 0.12 per 1,000 treatment days for patients who received IV epoprostenol (P<0.001). Mostly, the difference was due to gram-negative organisms (0.20 vs. 0.03 per 1000 treatment days; P<0.001). In multivariate analysis adjusting for age, year of BSI and cause of PAH, IV treprostinil was associated with a 3.08-fold increase in BSIs of any type and a 6.86-fold increase in gram-negative BSIs compared with epoprostenol (P<0.001 for both).
The authors noted that, during collection of the data in this study, two changes occurred in IV administration of prostanoids: use of a closed-hub catheter system was recommended, and the package insert for treprostinil was changed to recommend use of a certain diluent. More recent studies indicate the latter change may have helped lower BSI rates, and it's possible the former change has done the same, they noted. It's important to follow both of these practices, they added. “In addition, the data suggest that initial antibiotic therapy in a patient receiving IV treprostinil suspected of having a BSI should be initiated with a broad- spectrum antibiotic(s) with coverage for both gram-negative and gram-positive organisms, at least until specification and sensitivities of the organism(s) have been identified,” they wrote.
Guidance issued on educational interventions for ICD patients
The American Heart Association released a scientific statement on educational and psychological interventions for patients with implantable cardioverter defibrillators (ICDs).
An expert panel analyzed existing scientific evidence to examine psychological and quality-of-life outcomes after ICD receipt. The group also looked at data supporting interventions to improve ICD patients' educational and psychological needs, provided clinical recommendations for improving outcomes, and identified areas for future research. The statement was endorsed by the Heart Rhythm Society and the American Association of Critical-Care Nurses.
The clinical practice recommendations covered four categories: pre-implantation; post-implantation, early recovery and adjustment; ICD events; and end of life. They included the following:
- Emphasize the protective value of the ICD against sudden cardiac arrest but no effect on the underlying cardiac condition separate from biventricular pacing or other functions of the device, if present.
- Review the expected impact of the ICD on usual activities, including driving, travel, sexual and physical activity, and length of time for restrictions, if any.
- Provide instructions on wound care, medications, and pain and symptom management, and address concerns before hospital discharge.
- Provide a clear and succinct shock plan for what the patient and family are expected to do in the event of a shock.
- Promote problem solving, access to information, and ways to seek social support as problem-focused coping strategies. Consider structured support groups that focus on providing information and positive coping skills.
- Discuss the meaning of shocks with patients when they occur.
- Hold face-to-face discussions when possible with the patient and his or her family regarding the specifics of any advisory or recall.
- At end of life, review patient and family understanding of their disease, goals of care, and desired outcomes, as well as the relationship of the ICD to those stated goals. Discuss the potential to deactivate the shocking component of the ICD.
The panel experts recommended “that psychological and [quality-of-life] assessments be integrated into the designs of all mortality and morbidity focused clinical trials of new devices and ICD populations and that family members be included to the degree possible.”
The full statement was published in the Oct. 23, 2012 Circulation.
Decision tool in EHR improved dysphagia screening
An electronic clinical decision support tool increased dysphagia screening of ischemic stroke patients at one hospital.
Researchers designed a clinical decision support tool for dysphagia screening and then embedded it within their electronic medical record's stroke admission orders. They compared rates of swallow screening of ischemic stroke patients before and after implementation of the tool to assess whether clinicians were complying with this measure. A total of 706 ischemic patient events were studied using the decision support tool, and an additional 246 patients with hemorrhagic strokes were studied “to identify secular trends in care quality.”
Results were published in the December 2012 Stroke.
The pre-post study found a significant improvement in the percentage of ischemic stroke patients who were screened before any oral intake: from 36% to 74% (P=0.001). The study authors also looked at the rates of dysphagia screening among hemorrhagic stroke patients, who were typically admitted by surgical services that did not have access to the decision support tool. Screening rose from 4% to 28% among those patients, possibly due to increased hospital attention to this issue after an accreditation review identified it as an area of needed improvement, the authors speculated.
The study also included a random audit of 50 charts of patients treated after the intervention was implemented. The charts indicated that patients were more likely to be screened if they were admitted to the stroke unit or the stroke order set had been initiated. The researchers were not able to find any change in rates of pneumonia or mortality associated with the improvement in screening, however, possibly because there was insufficient power in the study. The authors concluded that dysphagia screening is a difficult measure to improve and this tool could potentially improve that situation for hospitals.
Probiotics lowered C. diff risk
Giving probiotics to patients taking antibiotics reduced the risk of Clostridium difficile-associated diarrhea (CDAD), according to a review.
Reviewers included 20 trials with more than 3,800 adult or pediatric patients who were receiving antibiotics and were randomized to a specified probiotic or placebo or no treatment control. They found that probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]). Results were published online by Annals of Internal Medicine on Nov. 13, 2012.
Assuming a 5% incidence of CDAD in patients taking antibiotics (the median risk in the studies' control groups), probiotic prophylaxis would prevent 33 cases of CDAD per 1,000 patients, the researchers calculated (95% CI, 25 to 38). Adverse events were lower in the probiotic-treated patients (9.3% vs. 12.6% of controls) and no trial reported a serious adverse event attributable to probiotics. Using multiple species of probiotics rather than a single species appeared to result in larger effects, but the finding was not consistent across studies, so further research is needed on this issue.
The authors concluded that moderate-quality evidence suggests a large reduction in CDAD from probiotic prophylaxis. A larger sample size would be required to rate the quality of the evidence as better than moderate, they noted. The review was limited by missing data on CDAD status in some patients. However, the authors conducted a stringent assessment of the worst-plausible assumptions with regard to that missing data and found the results still robust.
“Given the low cost of probiotics and the moderate-quality evidence suggesting the absence of important adverse effects, there seems little reason not to encourage the use of probiotics in patients receiving antibiotics who are at appreciable risk for CDAD,” the authors concluded.
New oral anticoagulants compared for stroke prevention in afib
Apixaban, rivaroxaban and dabigatran appeared to have similar efficacy for secondary stroke prevention in patients with atrial fibrillation, according to a recent analysis.
Researchers performed an indirect comparison analysis of apixaban versus two dosages of dabigatran and one dosage of rivaroxaban, plus rivaroxaban versus two dosages of dabigatran, to determine each drug's relative efficacy and safety. Data from the RE-LY, ROCKET-AF and ARISTOTLE trials, which were phase III randomized, controlled clinical trials of rivaroxaban, dabigatran or apixaban versus warfarin for stroke prevention in atrial fibrillation, were included. The researchers focused on the secondary prevention cohorts but also performed a secondary analysis of primary prevention cohorts. The study results were published online Nov. 5, 2012 by BMJ.
For secondary prevention, when apixaban was compared with dabigatran, 100 and 150 mg twice daily, the only significant difference in efficacy and safety was fewer myocardial infarctions (MIs) with apixaban versus the higher dabigatran dosage (hazard ratio, 0.39 [95% CI, 0.16 to 0.95]). Few significant differences in safety and efficacy were seen between apixaban or the higher dosage of dabigatran compared with rivaroxaban. Patients taking the lower dosage of dabigatran versus rivaroxaban had lower rates of hemorrhagic stroke, vascular death, major bleeding and intracranial bleeding.
For primary prevention, apixaban was better than the lower dosage of dabigatran for prevention of disabling or fatal stroke (hazard ratio, 0.59 [95% CI, 0.36 to 0.97]) but was associated with more stroke (hazard ratio, 1.45 [95% CI, 1.01 to 2.08]) and less bleeding (major, gastrointestinal and other location) than the higher dosage of dabigatran. The lower dosage of dabigatran was associated with more MIs than rivaroxaban. The main efficacy and safety endpoints did not differ significantly between rivaroxaban and the higher dosage of dabigatran, and no differences in the efficacy endpoints were seen between apixaban and rivaroxaban. Major bleeding appeared to be less common with apixaban than with rivaroxaban (hazard ratio, 0.61 [95% CI, 0.48 to 0.78]).
The authors acknowledged that the study was limited because it was an indirect comparison analysis but concluded that the three drugs had similar efficacy overall for the main endpoints in the secondary prevention cohorts. They noted, however, that hemorrhagic stroke, vascular death, major bleeding and intracranial bleeding occurred less often with the lower dosage of dabigatran than with rivaroxaban. In the primary prevention cohorts, some differences were observed among the drugs with relation to efficacy and bleeding outcomes. The authors called their results “hypothesis generating” and said they should be confirmed in a future randomized trial.
Framingham score may identify MI, death risks for stroke patients
The Framingham risk score may help identify recent stroke patients at elevated risk for heart attack or death, a recent study found.
Researchers retrospectively analyzed data on 3,509 ischemic stroke patients from 56 centers in the U.S., Canada and Scotland who were followed for two years. They categorized patients as having known coronary heart disease (CHD), high Framingham Coronary Heart Disease Risk Score or FCRS (≥20%), or low/intermediate FCRS (<20%). The primary outcome was myocardial infarction (MI), secondary outcome was MI or vascular death, and tertiary outcome was recurrent stroke. Researchers used multivariate analyses to determine predictive values between patients' baseline FCRS and the various outcomes. Results were published online Sept. 4 by Stroke.
Rates for first MI were 6.34% for known CHD, 4.65% for high FCRS and 1.44% for low/intermediate FCRS. Those with high FCRS had a significantly higher risk of MI than those with low/intermediate FCRS (adjusted hazard ratio [HR], 3.70; P<0.001) and a higher risk of MI or vascular death (HR, 2.21; P<0.001) over two years. Patients with known CHD also had significantly higher risk of MI (HR, 4.43; P<0.001) and MI or vascular death (HR, 3.37; P<0.001) compared to those with low/intermediate FCRS. Recurrent stroke risk didn't differ significantly between groups.
The findings suggest that, beyond its use for predicting long-term CHD risk in the general population, the FCRS may help predict MI risk, or risk of MI or vascular death, for recent stroke patients, the authors wrote. Patients found to be at risk may benefit from additional medications or diagnostic testing for silent cardiac ischemia, they wrote. The study is limited by its retrospective nature, the fact that data came from the early 2000s, and the fact that cardioembolic stroke patients were excluded, the authors noted.