In certain ACS patients, reduced-dose prasugrel beat standard-dose ticagrelor
In elderly or low-weight patients with acute coronary syndrome (ACS), a reduced dose of prasugrel compared with a standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting against excess bleeding risk, a subgroup analysis of a randomized trial found.
Researchers performed a prespecified analysis of the ISAR-REACT 5 randomized controlled trial, which was conducted at 23 centers in Germany and Italy. The trial randomly assigned patients with ACS undergoing percutaneous coronary intervention to receive a standard dose of ticagrelor or prasugrel (or a reduced dose of prasugrel in patients ages ≥75 years and those with a body weight <60 kg). The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was major bleeding, defined as Bleeding Academic Research Consortium type 3 to 5 bleeding, both at 12 months. Overall, the results showed that prasugrel was associated with improved outcomes in the composite end point without increasing the risk for major bleeding. The current analysis looked at the effect of the age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in the subset of elderly and low-weight participants. Results appeared in the Sept. 15, 2020, Annals of Internal Medicine.
A total of 3,997 patients were included in the analysis. Patients were categorized into an elderly or low-weight group (n=1,099) and a neither elderly nor low-weight group (n=2,898). The efficacy end point occurred in 12.7% of elderly or low-weight patients assigned to receive prasugrel and in 14.6% of those assigned to receive ticagrelor (148 events; hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]). In the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and in 7.3% of those assigned to receive ticagrelor (172 events; HR, 0.65 [95% CI, 0.48 to 0.88]; P>0.2 for interaction). Major bleeding occurred in 8.1% of elderly or low-weight patients assigned to receive prasugrel and in 10.6% of those assigned to receive ticagrelor (81 events; HR, 0.72 [95% CI, 0.46 to 1.12]) and in 3.7% and 3.8%, respectively, of patients in the neither elderly nor low-weight group (93 events; HR, 0.98 [95% CI, 0.65 to 1.47]; P>0.2 for interaction).
Among other limitations, the subgroup analysis of 27% of the trial population was underpowered for the efficacy and safety outcomes, the authors noted. “As a consequence, the study findings should be considered exploratory and hypothesis-generating,” they wrote.
In addition, adherence to the study medications was suboptimal, with about 40% to 43% of patients discharged alive from the index hospitalization discontinuing either study drug, an accompanying editorial noted. “Despite these limitations, these data provide important evidence supporting the modified dosing algorithm for prasugrel in elderly or underweight patients,” the editorialists wrote.
Readmission more likely in heart failure patients with low calorie consumption
An analysis of patients hospitalized with heart failure found that those who reported a history of low sodium consumption also had insufficient calorie intake and higher risk of readmission.
The study included 57 participants from GOURMET-HF (Geriatric OUt-of-hospital Randomized MEal Trial in Heart Failure). Prior to the start of the trial intervention (which involved home-delivered healthy meals after hospitalization), the participants' baseline nutritional intake was estimated using the Block Food Frequency Questionnaire and the Nutritional Risk Index (NRI). Their quality of life and readmission rate were measured at 12 weeks after hospitalization. Results were published in the Sept. 1, 2020, JACC: Heart Failure.
The patients' average age was 70 years, and 31% were women. Their mean body mass index was 32 kg/m2; they reported a daily median consumption of 2,987 mg of sodium (interquartile range [IQR], 2,160 to 3,540 mg/d) and 1,602 calories (IQR, 1,201 to 2,142 kcal/d). According to the NRI, 11% were malnourished. All of the patients who consumed less than 2,000 mg of sodium per day had insufficient calorie intake, and they were more likely to have diets deficient in micronutrients or protein. At 12 weeks, patients with insufficient calorie intake had less improvement in their quality of life since hospitalization (measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary) and higher odds of readmission (odds ratio, 14.5; 95% CI, 2.2 to 94.4) than those who consumed sufficient calories.
It's significant that these negative outcomes were associated with insufficient calorie consumption even in a population with a high prevalence of obesity, the study authors noted. “In addition to micronutrient deficits, it is possible that patients with HF [heart failure] who restricted sodium intake might not have consumed enough calories to maintain muscle mass and physical function, particularly in the vulnerable post-hospital setting,” they wrote. They did caution that the study could not show that the negative outcomes were a result of patients' consumption patterns.
“However, the authors believe the results of this study highlight the need for more comprehensive dietary counseling in patients with HF beyond sodium restriction,” they wrote, recommending that inpatient dietary assessment be used to improve readmission risk stratification and identify patients for nutritional intervention. This study's results support previous evidence showing benefits for heart failure patients from the Mediterranean and Dietary Approaches to Stop Hypertension diets, an accompanying editorial noted.
NSF rare with newer gadolinium-based contrast agents, review finds
Nephrogenic systemic fibrosis (NSF) occurs rarely with newer gadolinium-based contrast agents (GBCAs), but there's little evidence on the rate among patients with acute kidney injury or risk factors for chronic kidney disease (CKD), a study found.
Researchers reviewed 32 published articles to synthesize evidence about NSF risk with newer versus older GBCAs across the spectrum of kidney function. Twenty articles looked at NSF risk after exposure to newer GBCAs and 12 allowed comparison of NSF risk between newer and older GBCAs. The systematic review and evidence synthesis were published in the July 21, 2020, Annals of Internal Medicine.
In the 20 studies (n=83,291) analyzed to determine the occurrence of NSF per index exposure to newer GBCAs, no NSF cases developed (exact 95% CI, 0.0001 to 0.0258 case). Among the 12 studies (n=118,844) analyzed to compare the occurrence of NSF per index exposure to newer versus older GBCAs, 37 NSF cases developed after exposure to older GBCAs (exact 95% CI, 0.0001 to 0.0523 case) and four occurred (three confounded) after exposure to newer GBCAs (exact 95% CI, 0.0018 to 0.0204 case). Data were scant for patients with acute kidney injury or those at risk for CKD.
The authors wrote that although the review suggests that development of NSF after exposure to newer GBCAs is very rare, the available evidence in patient populations with mild kidney disease is too limited. They also noted that study heterogeneity prevented meta-analysis, and the risk of bias was high in most studies because of inadequate exposure and outcome ascertainment. They urged caution using GBCAs in patients with severely impaired kidney function and acute kidney injury because the exact clinical factors contributing to risk in these subpopulations remain unknown.
“Limited evidence suggests that additional studies in patient populations with mild kidney disease would substantially change these conclusions,” the authors wrote. “However, considering the scarcity of data about the use of newer and seemingly safer GBCAs among patients with advanced CKD, CKD risk factors, or acute kidney injury, further investigations in these populations are warranted and will require particular attention to comprehensive exposure and outcome assessment (such as documentation of all GBCA exposures and use of standardized diagnostic criteria for NSF).”
Endocarditis surgery shouldn't be delayed for antibiotics
Duration of preoperative antibiotic treatment did not correlate with the odds of positive valve culture in patients with infective endocarditis treated with surgical valve replacement in a recent study.
To evaluate the relationship between preoperative antibiotics and valve cultures, researchers retrospectively investigated 352 infective endocarditis episodes among 344 patients in a tertiary referral hospital from 2005 to 2016. The primary end point was positive valve culture results. Results were published in the July 7, 2020, Journal of the American College of Cardiology.
The odds ratios for a positive valve culture varied by two-day intervals of preoperative antibiotic treatment, ranging from 0.64 (95% CI, 0.61 to 0.68) at day 7 to 0.74 (95% CI, 0.70 to 0.78) at day 13 and 0.98 (95% CI, 0.93 to 1.02) at day 21. A multivariable analysis adjusted for bacterial species, McCabe-Jackson classification, and valve type resulted in odds ratios for positive valve culture of 6.35 (95% CI, 1.94 to 20.78; P=0.002) and 3.93 (95% CI, 1.57 to 9.84; P=0.003) for Enterococcus and Staphylococcus species, respectively.
The study authors noted that after seven days of antibiotic treatment, the additional effect of preoperative antibiotic treatment on valve culture results per two-day interval was minor. Antibiotic treatment beyond 21 days had no influence on culture results. They wrote, “The results of this study indicate that—in particular in staphylococcal and enterococcal infective endocarditis—achieving NVC [negative valve culture] should not be the primary influence on the decision for timing of valve surgery.”
An editorial noted that there was not a direct linear correlation between preoperative antibiotic duration and culture positivity. For staphylococcal and enterococcal infective endocarditis, negative valve culture should not primarily influence the decision making on the timing of valve surgery, and there are diminishing returns to longer antibiotic use, according to the editorial. “If an urgent indication for early surgery is present, the multidisciplinary clinical decision-making team should err on the side of early surgery. To delay surgery to ‘get more antibiotics on board’ is likely not going to lead to any additional patient benefit,” it said.
Another recent study of infective endocarditis found that the risk of this complication of streptococcal bloodstream infections is species dependent. Danish researchers studied national registries to investigate the risk of infectious endocarditis according to streptococcal species. Results were published in the Aug. 25, 2020, Circulation.
Prevalence of infective endocarditis was 7.1% (95% CI, 6.5% to 7.8%) among 6,506 cases of streptococcal blood stream infections. The lowest infective endocarditis prevalence was found with Streptococcus pneumoniae (1.2%; 95% CI, 0.8% to 1.6%) and S. pyogenes (1.9%; 95% CI, 0.9% to 3.3%). An intermediary prevalence was found with S. anginosus (4.8%; 95% CI, 3.0% to 7.3%), S. salivarius (5.8%; 95% CI, 2.9% to 10.1%), and S. agalactiae (9.1%; 95% CI, 6.6% to 12.1%). The highest prevalence was found with S. mitis/oralis (19.4%; 95% CI, 15.6% to 23.5%), S. gallolyticus (formerly S. bovis) (30.2%; 95% CI, 24.3% to 36.7%), S. sanguinis (34.6%; 95% CI, 26.6% to 43.3%), S. gordonii (44.2%; 95% CI, 34.0% to 54.8%) and S. mutans (47.9%; 95% CI, 33.3% to 62.8%).
A multivariable analysis using S. pneumoniae as reference showed that all species except S. pyogenes were associated with significantly higher infective endocarditis risk, with the highest risk found with S. mutans (odds ratio [OR], 81.3; 95% CI, 37.6 to 176), S. gordonii (OR 80.8; 95% CI, 43.9 to 149), S. sanguinis (OR, 59.1; 95% CI, 32.6 to 107), S. mitis/oralis (OR, 31.6; 95% CI, 19.8 to 50.5), and S. gallolyticus (OR, 31.0; 95% CI, 18.8 to 51.1).
Based on these results, it is reasonable to perform transthoracic echocardiography and transesophageal echocardiography in all patients with a bloodstream infection and high risk of infective endocarditis, the authors said. “In patients with streptococcal [bloodstream infections] with moderate IE [infective endocarditis] risk the decision to perform echocardiography should be carefully evaluated based on clinical suspicion and additional risk factors for IE,” they wrote. “In streptococci with a low IE prevalence it seems adequate to anticipate the clinical course and only perform echocardiography up front in case of either high or persistent clinical suspicion.”