Stroke imaging and AKI, beta-blockers after MI, and more.

Summaries from ACP Hospitalist Weekly.

Imaging not associated with increased AKI risk in stroke patients, study finds

Computed tomographic angiography (CTA) and computed tomographic perfusion (CTP) were not associated with increased risk for acute kidney injury (AKI) in patients with stroke, even in cases of known chronic kidney disease, a recent study has found.

Researchers performed a systematic review and meta-analysis to determine whether CTA/CTP led to increased AKI risk in patients with stroke. Studies published through December 2016 were included if they involved patients having imaging for acute ischemic stroke, had at least 50 patients in each treatment group for case-control studies or 50 patients in the CTA/CTP group for single-arm studies, and reported separate outcomes for patients having CTA/CTP and those having noncontrast CT. Primary outcomes were odds of AKI in patients receiving CTA/CTP compared with noncontrast CT, overall rate of AKI and hemodialysis in patients with acute ischemic stroke who had CTA/CTP, and odds of AKI associated with CTA/CTP in patients with and without chronic kidney disease. The study results were published online June 5, 2017, by Stroke and appeared in the July 2017 issue.

A total of 14 studies were included in the systematic review and meta-analysis, six of which were case-control studies and eight of which were single-arm studies. The studies included 5,727 patients undergoing CTA/CTP and 981 patients undergoing noncontrast CT. AKI was most commonly defined as a greater than 25% increase in creatinine level. In the case-control studies, incidence of AKI was significantly lower among patients receiving CTA/CTP versus patients receiving noncontrast CT (odds ratio, 0.47; 95% CI, 0.33 to 0.68; P<0.01). The researchers adjusted for baseline creatinine level and found no difference in AKI rates between groups (odds ratio, 0.34; 95% CI, 0.10 to 1.21). Among patients receiving CTA/CTP, the overall rate of AKI was 3% and the overall rate of hemodialysis was 0.07%. AKI rates did not differ in CTA/CTP patients with chronic kidney disease and CTA/CTP patients without chronic kidney disease (odds ratio, 0.63; 95% CI, 0.34 to 1.12).

The researchers noted that the evidence they analyzed was not from randomized controlled trials and that definitions of AKI and amount and type of contrast dye administered differed between studies, calling the certainty in their evidence low. However, they concluded that their results indicate a lack of association between contrast administration for CTA/CTP and risk for AKI in patients with acute ischemic stroke. “These findings suggest that delays in imaging and care because of absent or elevated creatinine values are not acceptable,” the authors wrote. “Concern about AKI should not deter physicians from pursuing their optimal imaging strategy for the management of patients with [acute ischemic stroke].” They called for future randomized controlled trials to confirm their results.

Beta-blockers not associated with lower risk of death after acute MI in patients without heart failure

Beta-blocker use was not associated with lower mortality up to one year after discharge in patients with acute myocardial infarction (MI) but without heart failure (HF), a recent study found.

Researchers used English and Welsh registry data to assess 179,810 patients with acute MI but not HF or left ventricular systolic dysfunction (LVSD) who survived hospitalization between Jan. 1, 2007, and June 30, 2013. They prospectively followed patients to determine the association between beta-blocker use and mortality at one year. Study results were published online on May 29, 2017, by the Journal of the American College of Cardiology and appeared in the June 6, 2017, issue.

Of 91,895 patients with ST-segment elevation MI (STEMI), 96.4% received beta-blockers, and of 87,915 patients with non-ST-segment elevation MI (NSTEMI), 93.2% received beta-blockers. Overall, 9,373 deaths (5.2%) occurred in the full cohort. In unadjusted analyses, the one-year mortality rate was lower among patients who received beta-blockers than among those who did not (4.9% vs. 11.2%; P<0.001).

However, in a propensity-score analysis including 24 variables (e.g., sex, discharge medications, cardiovascular risk factors), there was no significant difference in mortality between the groups (average treatment effect coefficient, 0.07; 95% CI, −0.60 to 0.75; P=0.827). The average treatment effect represents the absolute difference in survival time in months between beta-blocker treatment and no beta-blocker treatment.

The insignificant effect of beta-blockers on survival was also apparent at one month and six months after discharge, as well as in separate analyses of patients with STEMI and NSTEMI.

The study authors noted limitations, such as how they only studied patients who survived their hospitalization and that the registry data were only recorded during hospitalization. Thus, they were unable to capture new HF cases, medication discontinuation rates, or new prescriptions in the year after acute MI.

An accompanying editorial noted that the results should be interpreted with “extreme caution” because of the general limitations inherent to observational studies. The editorialists noted an additional limitation specific to this study: The left ventricular ejection fraction (LVEF) threshold used to define HF/LVSD was less than 30%. “The study thus includes patients with a post-MI LVEF of between 30% and 40%, for whom the clinical benefit of [beta]-blockers is clearly established,” they wrote.

The study should be considered hypothesis-generating and shouldn't change clinical practice, according to the editorialists. “However, this important report highlights the need to reboot the system: the role of [beta]-blockers in post-MI patients without LVSD (LVEF >40%) needs to be evaluated from scratch,” they wrote.

Algorithm appears to safely exclude PE, reduce need for imaging

An algorithm that uses differential D-dimer cutoffs at patient presentation appears to safely exclude pulmonary embolism (PE) while reducing the need for computed tomography pulmonary angiography (CTPA), according to a recent study.

Photo by Thinkstock
Photo by Thinkstock.

Researchers at 12 hospitals in the Netherlands performed a prospective cohort study to evaluate the YEARS algorithm, which combines three components of the original Wells clinical decision rule (clinical signs of deep venous thrombosis, hemoptysis, and likely diagnosis of PE) with varying D-dimer thresholds at presentation. PE was considered excluded in patients who had no YEARS items and a D-dimer level below 1,000 ng/mL and in patients who had one or more YEARS items and a D-dimer level below 500 ng/mL, while remaining patients underwent CTPA.

The study's primary outcome was number of independently adjudicated venous thromboembolism events during three-month follow-up after PE exclusion, while the secondary outcome was the number of required CTPAs with the YEARS algorithm versus the Wells clinical decision rule. The study results were published online May 23, 2017, by The Lancet and appeared in the July 15, 2017, issue.

Patients were recruited into the study from Oct. 5, 2013, to July 9, 2015. Of the 3,465 included patients, 456 (13%) received a PE diagnosis at baseline and 2,946 (85%) had PE excluded according to the YEARS algorithm. Mean patient age was 53 years, and 62% of patients were women. Eighteen patients in whom PE was excluded (either by the YEARS algorithm or by CTPA) received a diagnosis of venous thromboembolism during follow-up (0.61%; 95% CI, 0.36% to 0.96%), and of these, six had fatal PE (0.20%; 95% CI, 0.07% to 0.44%). CTPA was not indicated in 1,651 patients with the YEARS algorithm and 1,174 patients with the Wells clinical decision rule (48% vs. 34%; difference, 14% [95% CI, 12% to 16%]).

The authors noted that their study did not have a control group, that the study protocol was violated in 43 patients, and that they could not determine the safety of their algorithm in cancer patients, among other limitations. However, they concluded that the YEARS algorithm safely ruled out acute PE in patients in whom PE is clinically suspected and reduced imaging significantly.

The authors also noted that the age-adjusted D-dimer threshold was validated in a different study while their study was being conducted and pointed out that this threshold, if applied to their population, would have led to an absolute reduction in imaging of 8.7% (95% CI, 6.4% to 11%). They also stressed that the YEARS algorithm applies to patients of all ages and indicates an absolute risk reduction of 14% in patients younger than age 50, a group in which reduced exposure to radiation may be particularly relevant.

Adding ezetimibe to statin therapy after ACS may decrease hospitalizations, study finds

In patients with a recent acute coronary syndrome (ACS), adding ezetimibe to statin therapy may help reduce cardiovascular-related hospitalizations, according to a recent industry-funded study.

Researchers used patient-level data from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) to assess the impact of simvastatin (40 mg) and ezetimibe (10 mg) versus simvastatin and placebo on cardiovascular-related hospitalizations and related costs (except drug costs) over seven years of follow-up. Results of the study were published online on May 15 by Circulation: Cardiovascular Quality and Outcomes.

Among 18,144 IMPROVE-IT participants, there were 8,425 cardiovascular-related hospitalizations in the simvastatin–ezetimibe group and 8,943 in the simvastatin–placebo group.

Ezetimibe was associated with a 5% relative reduction in cardiovascular hospitalizations compared to placebo (risk ratio, 0.95; P=0.031), an effect mainly due to fewer hospitalizations for percutaneous coronary intervention, angina, and stroke/transient ischemic attack.

As a result, mean costs for cardiovascular hospitalization during follow-up were $453 lower per patient with ezetimibe compared to placebo ($7,276 vs. $7,729; P=0.030). The cost-savings trend emerged by the second year of treatment, and the majority of the cost offsets of simvastatin–ezetimibe were associated with coronary revascularization ($387 per patient; P=0.006).

High-risk subgroups of patients had more significant reductions in hospitalization costs with ezetimibe, including patients with diabetes (−$1,197 vs. −$264; P=0.024 for interaction), patients ages 75 years and older (−$1,584 vs. −$326; P=0.014 for interaction), and patients in the highest tertile of predicted risk for recurrent vascular events (−$1,701 vs. −$330 and $71 for the middle and lowest tertiles, respectively; P=0.001 for interaction).

The study authors noted that the cost reductions seen with ezetimibe could completely offset the cost of the drug once it is available as a generic (generic ezetimibe and simvastatin tablets were approved in April by the FDA). Health care systems “may derive substantial cost savings once generic ezetimibe is available by targeting its use to these highest-risk individuals,” they wrote.

Limitations of the study include IMPROVE-IT's multinational study design and the potential inaccuracies in applying U.S.-based cost estimates to hospitalizations in other countries (although there were no significant differences in ezetimibe's effect on hospitalization rates and costs between U.S. and non-U.S. enrollment sites).

The authors added that their cost analysis did not include data on outpatient care or indirect costs (e.g., lost productivity) and that simvastatin dose was increased from 40 mg to 80 mg in 27% of patients in the placebo group, compared with 6% in the ezetimibe group, which could lead to a conservative estimate of cost difference due to the potential for high simvastatin dose-related adverse effects.