Sacubitril-valsartan may be a cost-effective treatment for NYHA class II-IV heart failure patients
Sacubitril-valsartan is a novel medication found to treat heart failure with reduced ejection fraction. Following a randomized, double blind trial (PARADIGM-HF), sacubitril-valsartan was shown to reduce cardiovascular mortality, decrease hospitalizations, and improve quality of life, compared with the current standard of practice – lisinopril. However sacubitril-valsartan is substantially more expensive than lisinopril, and this study assessed the cost-effectiveness of sacubitril-valsartan compared to usual care in a cohort of patients with NYHA class II to IV heart failure. The authors of this study employed a Markov decision model to assess cost-effectiveness of sacubitril-valsartan in patients with average age of 64 years of age with an ejection fraction of 0.4 or less and NYHA class II to IV heart failure and compared outcomes in terms of cost, life-years, quality-adjusted life years (QALYs), and heart failure. Results of the base-case analysis showed that the sacubitril-valsartan group experienced 0.08 fewer heart failure hospitalizations, 0.69 additional life-year, 0.62 additional QALY, and $29,203 in incremental costs, equating to a cost per QALY gained of $47,053. The cost per QALY gained was $44,531 in patients with NYHA class II heart failure and $58, 194 in those with class III or IV heart failure. The authors concluded that treatment with sacubitril-valsartan provides reasonable value in reducing cardiovascular mortality and morbidity in patients with NYHA class II to IV heart failure.
It is known that long acting beta-agonists (LABAs) have been shown to increase the risk of asthma related death among adults and hospitalizations in children however, it is unknown whether concomitant use of inhaled glucocorticoids and LABAs lessens those risks. The purpose of this trial was to prospectively evaluate the safety of LABA salmeterol added to fluticasone propionate in a fixed dose combination in children. This was a randomized, double blind, active comparator trial randomized 6208 children aged 4-11 years of age to receive either fluticasone-salmeterol therapy (n=3107) or fluticasone monotherapy (n= 3101) for 26 weeks. The primary outcome was first adverse asthma-related event (death, intubation, hospitalization). The study showed that of the 6208 patients, 27 patients in the fluticasone–salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event, with a hazard ratio in fluticasone–salmeterol versus fluticasone alone of 1.28 (95% confidence interval: 0.73 to 2.27). The only serious asthma related event reported was hospitalization (there were no intubations or asthma related deaths). A total of 265 patients (8.5%) in the fluticasone–salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI: 0.73 to 1.01). As a result, the authors concluded that in this trial, salmeterol in fixed dose combination with fluticasone in children was associated with similar risk of serious asthma related event as that of fluticasone alone.
Breast density and risk may guide mammography screening frequency
Although the United States Preventative Services Task Force recommend biennial breast cancer screening for average risk women aged 50 to 64 years old, little data exists regarding alternative screening interventions. The purpose of this study was to evaluate outcomes of three screening intervals- annual, biennial, and triennial in women over 50 years of age based on breast density and risk for breast cancer. In this collaborative simulation model using national incidence, breast density, and screening performance data, lifetime breast cancer deaths, life expectancy, quality adjusted life years (QALYs), false positive mammograms, benign biopsy results, overdiagnosis, cost-effectiveness, and ratio of false positive results to breast cancer deaths averted were compared in women age 50-74 with annual, biennial, or triennial mammography screening (vs no screening) and ages 65-74 (vs biennial mammography from ages 50 to 64 years). The study showed that among women with average-risk (RR of 1.0 to 1.3) and low breast density, triennial screening resulted in a similar number of breast cancer deaths averted compared to biennial screening for all age groups (50 to 74 years, median of 3.4 to 5.1 vs. 4.1 to 6.5 deaths averted; 65 to 74 years, median of 1.5 to 2.1 vs. 1.8 to 2.6 deaths averted). Comparatively, annual versus biennial screening increased the number of breast cancer deaths averted for women aged 50 to 74 years with any level of breast density and an RR of 4.0, or women aged 65 to 74 years with an RR of 4.0 combined with high breast density.
Prolonged DAPT following PCI linked to fewer ischemic events in patients with PAD
The optimal duration of dual antiplatelet therapy (DAPT) following PCI balances the benefits of preventing further ischemic events against bleed risk. This study assessed the efficacy and safety of prolonged (24 month) compared to short (<6 months) term use of DAPT in patients with peripheral arterial disease (PAD) undergoing PCI. This is a subgroup analysis of the randomized Polonging Dual Antiplatelet Treatment After Grading Stent- Induced Intimal Hyperplasia Study (PRODIGY) trial and compared patients with baseline PAD (n=246) to those without (n=1724) and patients were followed for 24 months after PCI with primary outcome defined as a composite of death, myocardial infarction, or cerebrovascular accident while safety endpoint of bleeding was evaluated using Bleeding Academic Research Consortium Criteria.  The authors found that status of PAD was associated with a higher risk of death and ischemic events (hazard ratio [HR], 2.80; 95% CI: 2.05-3.83; P  < 0 .001). In addition, prolonged vs short DAPT conveyed a lower risk of the primary efficacy end point in patients with PAD (19 [16.1%] vs 35 [27.3%]; HR, 0.54; 95% CI, 0.31-0.95; P = .03) but not in patients without PAD (81 [9.3%] vs 63 [7.4%]; HR, 1.28; 95% CI, 0.92-1.77; P = .15). Finally, Bleeding Academic Research Consortium type 2, 3, or 5 bleeding occurred in 6 patients with PAD (5.2%) receiving prolonged DAPT relative to 8 (6.9%) of those receiving short DAPT (HR, 0.77; 95% CI, 0.27-2.21; P = .62). The authors concluded that PAD confers poor prognosis in patients undergoing PCI and that prolonged DAPT lowers the risk of ischemic events with no apparent bleeding liability in this high risk group.
Early ART therapy for HIV-1 linked to decreased transmission: The HPTN 052 trial
An analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed the benefit of antiretroviral therapy (ART) in preventing HIV type 1 in serodiscordant couples. This study reports the 5 year results from the HPTN trial where a total of 1763 patients were randomized to either early (n=886) or delayed (n=877) ART. Delayed initiation of treatment was initiated in patients when two consecutive CD4 counts fell below 250 or if an illness indicative of AIDS developed. The author’s primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1 negative partner. Since the interim analysis revealed that early ART prevented 96% of genetically linked infections, patients in the delayed treatment arm were offered treatment. The authors found that across both groups, 78 HIV-1 partner infections were observed with viral linkage established in 92% of these patients. There was also a 93% lower risk of linked partner HIV infection in the early ART group compared to delayed ART (hazard ratio, 0.07; 95% CI: 0.02 to 0.22). As a result, the authors concluded that early initiation of ART was associated with a decrease in genetically linked HIV-1 infection in sexual partners compared to delayed ART initiation.
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