2 Minute Medicine Rewind September 3, 2018

Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy

New treatments are needed for transthyretin amyloid cardiomyopathy, a disease characterized by the accumulation of amyloid fibrils in the heart. Tafamidis, a nonsteroidal anti-inflammatory drug, has been proposed as a treatment. In this randomized controlled trial, 441 patients with transthyretin amyloid cardiomyopathy were randomized to receive 80 mg tafamidis, 20 mg tafamidis or placebo in order to study the effect of tafamidis on all-cause mortality and the frequency of cardiovascular-related hospitalizations. Researchers found that all-cause mortality was lower in patients that received tafamidis when compared to placebo (HR 0.70, 95% CI 0.51 to 0.96). The rate of cardiovascular-related hospitalizations was also lower (0.48 vs. 0.70 hospitalizations per year, RR 0.68, 95% CI 0.56 to 0.81). In terms of secondary outcomes, tafamidis decreased the decline in distance walked during a 6-minute walk test for treated patients (difference of 75.68 m, standard error 9.24 m, p<0.001). Tafamidis also decreased the decline in KCCQ-OS score, a quality-of-life measure for patients with congestive heart failure (difference 13.65, standard error 2.13, p<0.001). No meaningful difference was found with respect to safety when comparing the two doses of tafamidis, and permanent discontinuation of treatment due to adverse events occurred less frequently in the tafamidis group than the placebo group. Taken together, the results of this study suggest that tafamidis may have a role in treating transthyretin amyloid cardiomyopathy, although further investigation with administration earlier during the disease course could better characterize the benefit of tafamidis treatment.

Obesity and loss of disease-free years owing to major non-communicable diseases: a multicohort study

There is little data available on the variation of obesity-related loss of disease-free years across different socioeconomic groups and lifestyle categories. In this cohort study, investigators analyzed records from 137,503 participants and calculated body mass index (BMI) values in order to study the effect of BMI on the first record of certain non-communicable diseases including, incident type 2 diabetes, coronary heart disease, cancer, asthma, chronic obstructive pulmonary disease (COPD). Researchers found that between 40 and 75 years, normal-weight men and women had a mean of 29.3 disease-free years (95% CI 28.8 years to 29.8 years) and 29.4 years (95% CI 28.7 years to 30.0 years), respectively. Compared with normal-weight men, overweight men lost 1.1 disease-free years (95% CI 0.7 years to 1.5 years), class I obese men lost 3.9 disease-free years (95% CI 2.9 years to 4.9 years), and class II-III obese men lost 8.5 disease-free years (95% CI 7.1 years to 9.8 years). Compared to normal-weight women, overweight women lost 1.1 disease-free years (95% CI 0.6 years to 1.5 years), class I obese women lost 2.7 disease-free years (95% CI 1.5 years to 3.9 years), and class II-III obese women lost 7.3 disease-free years (95% CI 6.1 years to 8.6 years). When researchers conducted stratified analyses across socioeconomic level, smoking habits, and physical activity level, they replicated the association between BMI category and loss of disease-free years; the loss of disease-free years for individuals with class II-III obesity varied between 7.1 years to 10.0 years for subgroups. Overall, results from this study indicate that mild and severe obesity are associated with a reduction in disease-free years between 40 years and 75 years; there are also associations between disease-free years and socioeconomic status, physical activity, and smoking. This study was limited in that a “loss of disease-free years” occurred only with the incidence of a limited number of major chronic diseases as per study definitions.

Partial oral versus intravenous antibiotic treatment of endocarditis

The current treatment of left-sided infective endocarditis involves intravenous antibiotics for up to 6 weeks, requiring many patients to stay in hospital. In this randomized controlled trial, investigators randomized 400 patients with left-sided infective endocarditis who were receiving intravenous antibiotics to continue intravenous treatment or switch to oral antibiotic treatment in order to study the effect of oral antibiotics on a composite outcome including all-cause mortality, unplanned cardiac surgery, clinically evident embolic events, or relapse of bacteremia with the primary responsible pathogen. Researchers found that there was not a significant difference in the incidence of the primary composite outcome, which occurred in 12.1% of patients in the intravenously treated group and in 9.0% of the orally treated group (OR 0.72, 95% CI 0.37 to 1.36). Four patients in the oral treatment group were switched to intravenous therapy, however, results from a sensitivity analysis in which these patients were considered to have treatment failure, still met the criterion for noninferiority. There were no statistically significant differences in unplanned cardiac surgery, embolic events, relapse of the positive blood culture, or all-cause mortality. Overall, results from this study indicate that for patients with left-sided infective endocarditis who are in stable condition, oral administration of antibiotics is non-inferior to intravenous administration. It is important to note, however, that the criteria for inclusion in this trial were strict, as only patients infected with certain bacterial species were eligible who were in stable condition were enrolled. Oral antibiotic regimens were also developed by the investigators and only included antibiotics with good oral bioavailability. As such, generalization of these results requires further investigation.

Association of Rapid Molecular Testing With Duration of Respiratory Isolation for Patients With Possible Tuberculosis in a US Hospital

Rapid molecular testing has been proposed as a replacement for serial sputum collection in the diagnosis of active tuberculosis (TB), although its impact on routine practice is unknown. In this prospective cohort study, investigators analyzed data from 621 patients for whom TB sputum examinations were ordered during either a pre-implementation or post-implementation period of rapid molecular testing to evaluate the implementation and impact of a molecular testing strategy to guide discontinuation of isolation. The outcomes examined included the number of molecular tests ordered and completed, the accuracy of the molecular testing algorithm, the time patients spent in isolation, and estimated mean costs. Researchers found that 71% of patients in this study had molecular assay results, with 4.3% of patients in the pre-implementation period and 2.7% of patients in the post-implementation period producing positive rapid molecular test results. For sputum culture, 3.4% of patients evaluated in the pre-implementation period and 2.7% evaluated during the post-implementation period had positive culture results.  All patients in the post-implementation period with a positive culture result also had a positive rapid molecular test result, and the molecular testing algorithm excluded TB in all patients with culture-negative results. For all patients, the median duration of respiratory isolation decreased from 2.9 days (IQR 2.0 days to 3.7 days) to 2.5 days (IQR 1.7 to 3.4 days) after implementation (p=0.001). For patients with negative rapid TB test results, mean time in isolation decreased by 29% (p=0.03), mean time in hospital length of stay decreased by 27% (p=0.01), and estimated mean hospital costs decreased from $4,6921 to $33,574. Overall, results from this study suggest that the implementation of rapid molecular testing to guide discontinuation of respiratory isolation for patients undergoing evaluation for active TB is feasible, providing significant clinical and economic benefits. It should be noted, however, that this study was conducted at a single academic center with clinicians who were free to decide whether to use the molecular assay results to guide discontinuation of isolation. As such, further studies are needed to generalize results and establish guidelines for when to discontinue isolation.

Double-Blind Randomized Clinical Trial of Prazosin for Alcohol Use Disorder

Prazosin, an α-1 adrenoceptor antagonist, has been proposed in reducing alcohol use, as brain noradrenergic activity has been implicated in the initiation and maintenance of alcohol use disorder. In this randomized controlled trial, investigators randomized 92 individuals with alcohol use disorder to receive either prazosin or placebo in order to study the effect of prazosin on the number of alcoholic drinks consumed per week, number of drinking days per week, and number of heavy drinking days per week over 12 weeks. Researchers found that there was no significant difference between the placebo and prazosin groups for number of drinking days, while there were significant interactions between condition and week for number of heavy drinking days (p=0.01) and number of drinks per week (p=0.03). The prazosin group had a more rapid decrease in the number of heavy drinking days from the first post-titration week (week 3) to week 12 than the placebo group (0.8 days and 0.3 days, respectively; 95% CI for difference 0.0, 0.8). For the prazosin group, the odds of heavy drinking were 0.85 (95% CI 0.80 to 0.91) times the odds of heavy drinking from the previous week while the placebo group had odds of 0.95 (95% CI 0.90 to 1.0) times the odds of heavy drinking from the previous week (OR 0.90, 95% CI 0.82 to 0.98). The prazosin group also had a more rapid decrease in number of drinks per week (reduction of 8.0 drinks from week 3 to week 12, 95% CI 1.8 drinks to 19.5 drinks) than the placebo group (reduction of 1.5 drinks from week 3 to week 12, 95% CI -3.4 drinks to 6.8 drinks). The rate of drinking decreased more for the prazosin group (5% decrease versus 1% decrease, difference 4%, 95% CI 0.3% to 7.7%). Overall, the results of this study indicate that prazosin may have a role in the treatment of alcohol use disorder. It is important to note, however, that at the first post-titration week, the prazosin group had a higher mean number of drinks per week, number of drinking days, and number of heavy drinking days than the placebo group; the number of heavy drinking days and number of drinks per week did not differ between conditions at week 12. Replication of this study and further research into dosing regimens would be useful to support prazosin as a treatment for alcohol use disorder.

Image: PD

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