Redo-aortic valve replacement in prior stentless prosthetic aortic valves: Transcatheter versus surgical approach.

OBJECTIVES: The objective was to compare outcomes of redo-aortic valve replacement (AVR) via surgical or transcatheter approach in prior surgical AVR with large percentage of prior stentless surgical AVR. BACKGROUND: With the introduction of transcatheter aortic valve replacement (TAVR), patients with increased surgical risks now have an alternative to redo surgical AVR (SAVR), known as valve-in-valve (ViV) TAVR. Stentless prosthetic aortic valves present a more challenging implantation for ViV-TAVR given the lack of structural frame. METHODS: We performed a retrospective study of 173 subjects who have undergone SAVR (N = 100) or ViV-TAVR (N = 73) in patients with prior surgical AVR at Wake Forest Baptist Medical Center from 2009 to 2019. Our study received the proper ethical oversight. RESULTS: The average ages in redo-SAVR and ViV-TAVR groups were 58.03 ± 13.86 and 66.57 ± 13.44 years, respectively (p < 0.0001). The redo-SAVR had significantly lower STS (2.78 ± 2.09 and 4.68 ± 5.51, p < 0.01) and Euroscores (4.32 ± 2.98 and 7.51 ± 8.24, p < 0.05). The redo-SAVR group had higher percentage requiring mechanical support (8% vs. 0%, p < 0.05) and vasopressors (53% vs. 0%, p < 0.0001), longer length of stay (13.65 ± 11.23 vs. 5.68 ± 7.64 days, p < 0.0001), and inpatient mortality (16% vs. 2.78%, p < 0.005). At 30-day follow-up, redo-SAVR group had higher rates of acute kidney injury (10% vs. 0%, p < 0.01), however ViV-TAVR group had more new left bundle branch blocks (6.85% vs. 0%, p < 0.05). No significant differences regarding re-hospitalization rates, stroke, or death up to 1-year. CONCLUSION: Although the ViV-TAVR group had higher risk patients, there were significantly fewer procedural complications, shorter length of stay, and similar mortality outcomes up to 1-year follow-up.

Reduction in the severity and duration of headache following fremanezumab treatment in patients with episodic and chronic migraine.

OBJECTIVE: To evaluate the impact of fremanezumab on the severity and duration of remaining migraine attacks in patients with chronic migraine (CM) or episodic migraine (EM). BACKGROUND: Fremanezumab is a fully humanized monoclonal antibody (IgGΔa) that selectively targets calcitonin gene-related peptide and is efficacious in reducing migraine frequency. METHODS: This exploratory post hoc analysis included data from three randomized, double-blind, 12-week, phase 3 studies (HALO CM, HALO EM, and FOCUS). In all three studies, patients with CM or EM were randomized 1:1:1 to receive subcutaneous quarterly fremanezumab (month 1/2/3: 675 mg/placebo/placebo), monthly fremanezumab (month 1/2/3: 675 mg [CM], 225 mg [EM]/225 mg/225 mg), or matched monthly placebo. Changes from baseline were evaluated in the proportion of headache days of at least moderate severity, peak severity of headache days, mean monthly headache hours (of any severity and at least moderate severity), and mean headache hours per headache day of any severity. RESULTS: A total of 2843 patients were randomized with 2823 patients included in the efficacy analyses across all studies (HALO CM, N = 1121; HALO EM, N = 865; FOCUS, N = 837). At study baseline, mean (standard deviation [SD]) monthly number of headache days rated moderate or severe in the quarterly fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 13.2 (5.5), 12.8 (5.8), and 13.3 (5.8) in HALO CM; 7.2 (3.1), 6.8 (2.9), and 6.9 (3.1) in HALO EM; and 12.4 (5.8), 12.7 (5.8), and 12.8 (5.9) in FOCUS. Patients experienced significant least-squares mean (LSM; 95% confidence interval) percent reductions from baseline in monthly number of headache days rated moderate or severe during the 12 weeks: HALO CM, quarterly fremanezumab, 34.5% (-39.8, -29.2) and monthly fremanezumab, 36.2% (-41.4, -31.0) vs. placebo, 19.6% (-20.0, -14.3); HALO EM, quarterly fremanezumab, 40.7% (-47.8, -33.5) and monthly fremanezumab, 43.4% (-50.4, -36.3) vs. placebo, 17.9% (-24.9, -11.0); and FOCUS, quarterly fremanezumab, 36.5% (-41.9, -31.1) and monthly fremanezumab, 38.6% (-44.0, -33.3) vs. placebo, 3.5% (-8.9, 1.8); all p < 0.0001. At study baseline, mean (SD) number of monthly headache hours rated moderate or severe in the quarterly fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 66.4 (58.8), 68.0 (53.9), and 68.5 (57.0) in HALO CM; 33.3 (25.4), 31.7 (23.7), and 31.6 (23.2) in HALO EM; and 59.2 (54.7), 64.3 (65.2), and 65.9 (70.2) in FOCUS. Significant reductions were observed in LSM (standard error) number of monthly headache hours of at least moderate severity: HALO CM, quarterly fremanezumab, 24.4 (2.5) and monthly fremanezumab, 26.4 (2.3) vs. placebo, 14.1 (2.5); HALO EM, quarterly fremanezumab, 14.5 (1.4) and monthly fremanezumab, 15.5 (1.3) vs. placebo, 8.1 (1.3); and FOCUS, quarterly fremanezumab, 16.8 (3.0) and monthly fremanezumab, 18.3 (3.0) vs. placebo, 2.3 (3.0); all p < 0.001. CONCLUSION: These analyses demonstrated that quarterly or monthly treatment with fremanezumab significantly reduced headache severity and duration in patients with CM or EM, including in patients with documented inadequate response to two to four prior migraine preventive medication classes.

Treatment benefit among migraine patients taking fremanezumab: results from a post hoc responder analysis of two placebo-controlled trials.

BACKGROUND: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, including the fully humanized monoclonal antibody (IgG2Δa) fremanezumab, have demonstrated safety and efficacy for migraine prevention. Clinical trials include responders and nonresponders; efficacy outcomes describe mean values across both groups and thus provide little insight into the clinical benefit in responders. Clinicians and their patients want to understand the extent of clinical improvement in patients who respond. This post hoc analysis of fremanezumab treatment attempts to answer this question: what is the benefit in subjects who responded to treatment during the two, phase 3 HALO clinical trials? METHODS: We included subjects with episodic migraine (EM) or chronic migraine (CM) who received fremanezumab quarterly (675 mg/placebo/placebo) or monthly (EM: 225 mg/225 mg/225 mg; CM: 675 mg/225 mg/225 mg) during the 12-week randomized, double-blind, placebo-controlled HALO EM and HALO CM clinical trials. EM and CM responders were defined as participants with a reduction of ≥ 2 or ≥ 4 monthly migraine days, respectively. Treatment benefits evaluated included reductions in monthly migraine days, acute headache medication use, and headache-related disability, and changes in health-related quality of life (HRQoL). RESULTS: Overall, 857 participants from the HALO trials were identified as responders (EM: 429 [73.8%]; CM: 428 [56.7%]). Reductions in the monthly average number of migraine days were greater among EM (quarterly: 5.4 days; monthly: 5.5 days) and CM (quarterly: 8.7 days; monthly: 9.1 days) responders compared with the overall population. The proportion of participants achieving ≥ 50% reduction in the average monthly number of migraine days was also greater in responders (EM: quarterly, 59.8%; monthly, 63.7%; CM: quarterly, 52.8%; monthly, 59.0%) than in the overall population. Greater reductions in the average number of days of acute headache medication use, greater reductions in headache-related disability scores, and larger improvements in HRQoL were observed among EM and CM responders compared with the overall populations. CONCLUSIONS: Fremanezumab responders achieved clinically meaningful improvements in all outcomes. The magnitude of improvements with fremanezumab across efficacy outcomes was far greater in responders than in the overall trial population, providing insight into expected treatment benefits in participants who respond to fremanezumab in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02629861 (HALO EM) and NCT02621931 (HALO CM).

Assessment of the prognostic significance of low gradient severe aortic stenosis and preserved left ventricular function requires the integration of the consistency of stroke volume calculation and clinical data.

BACKGROUND: This study was to evaluate the prognostic significance of low gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF) with the integration of echocardiographic and clinical data. METHODS: The study included 172 patients with LG SAS (AVAi ≤ 0.6 cm2 /m2 , mean aortic pressure gradient < 40 mm Hg) and LVEF (≥ 50%). LV outflow tract diameters were measured at both the aortic valve annulus and 5 mm below the annulus for the measurement consistency. Patients were divided into the low flow LG SAS (LF/LG SAS: SVi < 35mL/m2 and AVAi ≤ 0.6 cm2 /m2 ) and normal-flow LG SAS groups (NF/LG SAS: SVi ≥ 35mL/m2 and AVAi ≤ 0.6 cm2 /m2 ). Echocardiographic findings and clinical data were systematically analyzed with mean follow-up of 3.0 ± 1.6 years. RESULTS: LF/LG SAS had significantly smaller AVAi, lower SVi, a higher prevalence of atrial fibrillation (28% vs 12% P = .01) and diabetes (47% vs 27% P = .007) and lower 3-year cumulative survival than NF/LG SAS. Multivariable analysis showed that dyspnea, renal dysfunction (CI 1.42-3.99, P < .01), left atrial diameter, and SVi were independently associated with an increased risk for all-cause mortality. Aortic valve intervention (AVI) improved survival in LF/LG SAS (68% vs 48%, P < .05) in comparison with medical management (HR: 4.20, CI: 1.12-15.76, P = .03), but only modestly in NF/LG SAS (75% vs 65% P > .05). CONCLUSION: Outcome of LG SAS was independently associated with clinical characteristics. AVI likely improved outcome of LF/LG SAS who had high-risk clinical characteristics and unfavorable echocardiographic findings.

Improvements across a range of patient-reported domains with fremanezumab treatment: results from a patient survey study.

BACKGROUND: The long-term safety and efficacy of fremanezumab were evaluated in a 52-week extension study (NCT02638103). Patient satisfaction with fremanezumab, dosing preferences, and patient-reported outcomes were assessed in a subpopulation who completed the extension study and consented to a follow-up questionnaire. METHODS: In the extension study (N = 1842), adults with migraine were randomized to quarterly or monthly fremanezumab. After completing active treatment, patients answered a survey evaluating patient satisfaction, treatment and dosing preferences, and changes in patient-reported outcomes. RESULTS: Of the 557 patients who could have been contacted upon completing the extension study, 302 consented and 253 completed the survey. The mean (standard deviation) satisfaction rating for fremanezumab was 6.1 (1.4; 1 = "extremely dissatisfied" to 7 = "extremely satisfied"). Most patients (175 [69.2%]) preferred quarterly over monthly fremanezumab dosing. Among patients taking antiepileptics (most common class of prior preventive medication; n = 130), 91.5% preferred fremanezumab. Patients reported improvements in anxiety (74 [67.9%]), sleep quality (143 [56.5%]), and quality of time spent with others (210 [83.0%]) with fremanezumab. CONCLUSION: In this study, treatment satisfaction with fremanezumab was high, most patients preferred quarterly fremanezumab dosing, and fremanezumab was generally preferred to prior preventive medications. TRIAL REGISTRATION: ClinicalTrials.gov NCT02638103 (HALO LTS), registered December 22, 2015.

A comparison of valve-in-valve transcatheter aortic valve replacement in failed stentless versus stented surgical bioprosthetic aortic valves.

OBJECTIVES: The objectives of this study were to compare short- and intermediate-term clinical outcomes, procedural complications, TAVR prosthesis hemodynamics, and paravalvular leak (PVL) in stentless and stented groups. BACKGROUND: Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) is an alternative to surgical redo for bioprosthetic valve failure. There have been limited data on ViV in stentless surgical valves. METHODS: We retrospectively analyzed 40 patients who underwent ViV TAVR in prior surgical bioprosthetic valves at Wake Forest Baptist Medical Center from October 2014 to September 2017. Eighty percent (32/40) ViV TAVRs were in stentless, while 20% (8/40) were in stented bioprosthetic valves. RESULTS: The primary mode of bioprosthetic valve failure for ViV implantation in the stentless group was aortic insufficiency (78%, 25/32), while in the stented group was aortic stenosis (75%, 6/8). The ViV procedure success was 96.9% (31/32) in stentless group and 100% in stented group (8/8). There were no significant differences in all-cause mortality at 30 days between stentless and stented groups (6.9%, 2/31 versus 0%, 0/8, P = 0.33) and at 1 year (0%, 0/25 versus 0%, 0/5). In the stentless group, 34.4% (11/32) required a second valve compared to the stented group of 0% (0/8). There was a significant difference in the mean aortic gradient at 30-day follow-up (12.33 ± 6.33 mmHg and 22.63 ± 8.45 mmHg in stentless and stented groups, P < 0.05) and at 6-month follow-up (9.75 ± 5.07 mmHg and 24.00 ± 11.28 mmHg, P < 0.05), respectively. CONCLUSIONS: ViV in the stentless bioprosthetic aortic valve has excellent procedural success and intermediate-term results. Our study shows promising data that may support the application of TAVR in stentless surgical aortic valve. However, further and larger studies need to further validate our single center's experience.

Effect of tardive dyskinesia on quality of life in patients with bipolar disorder, major depressive disorder, and schizophrenia.

PURPOSE: Tardive dyskinesia (TD) is a common but serious hyperkinetic movement disorder and side effect of antipsychotic medications used to treat bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ). The purpose of this study was to evaluate health-related quality of life (HRQoL) in a population with diagnoses for BD, MDD, or SZ by comparing patients with TD (n = 197) with those without TD (n = 219). HRQoL in each group was also compared with HRQoL of the general population. METHODS: This study employed a cross-sectional web-based survey. HRQoL was assessed by four instruments: the SF-12 Health Survey, Version 2 (SF-12v2), the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF), the Social Withdrawal subscale of the Internalized Stigma of Mental Illness Scale (SW-ISMI); and two questions on movement disorders. RESULTS: Patients with TD had significantly worse HRQoL and social withdrawal than those without. The differences were more pronounced for physical HRQoL domains than for mental health domains. Patients with more-severe TD, assessed through either self-rating or clinician rating, experienced significantly worse HRQoL than did those with less-severe TD. The impact of TD was substantially greater in patients with SZ than in those with BD or MDD. Compared with the general population, patients with BD, MDD, or SZ experienced significantly worse HRQoL regardless of TD status, although this deficit in HRQoL was greater among those with TD. CONCLUSIONS: The presence of TD is associated with worse HRQoL and social withdrawal. The most severe impact of TD is on physical aspects of patients' HRQoL.

Comparison of outcomes with surgical cut-down versus percutaneous transfemoral transcatheter aortic valve replacement: TAVR transfemoral access comparisons between surgical cut-down and percutaneous approach.

OBJECTIVES: The objective is to compare the short-term (30 days) and late (12 months) vascular adverse events in patients undergoing transfemoral (TF)-transcatheter aortic valve replacement (TAVR) by surgical cut-down (SC) vs. percutaneous (PC) approaches. BACKGROUND: Programs continue to utilize both approaches in TF-TAVR. There are limited data comparing outcomes by SC vs. PC approaches and long-term effects of endovascular intervention facilitated hemostasis on late vascular adverse events. METHODS: A total of 146 men and women aged 79.7 ± 10.0 years with severe aortic stenosis deemed extreme or high risk for surgery underwent TAVR via TF access. 61 had SC and 85 had PC approaches. Valve Academic Research Consortium (VARC-2) outcomes were assessed at an average of 12.1 months after TAVR. RESULTS: Hospital length of stay (LOS) post-TAVR was shorter for the PC group compared to the SC group (5.1 ± 3.9 vs. 8.2 ± 6.6 days; P < 0.001). More patients were discharged directly to home in the PC than the SC group (85.9% vs. 68.9%, P < 0.05). At 30 days, there were 13/61 (21.3%) and 16/85 (18.8%; P < 0.05) of any vascular events, and 2/61 (3.3%) and 2/85 (2.4%; P = 0.73) major vascular events in the SC and PC groups, respectively. There was no difference in all-cause mortality between the SC (14/61; 23%) and PC groups [17/85 (20%); P = 0.34]. There was no difference in any [4/33 (12%) vs. 3/43 (7%); P = 0.84] or major vascular adverse events [1/33 (3%) vs. 1/43 (2%); P = 0.79] in subjects that underwent adjunctive endovascular intervention compared to those who did not, respectively. There were no statistically significant univariate or multivariate predictors of any vascular event at 12 months when comparing SC to PC groups. CONCLUSION: For TF TAVR, the PC approach, when compared to the SC approach, is associated with a shorter hospital LOS and higher rate of direct discharge to home with similar risk of vascular complications, late vascular adverse events, and all-cause mortality at 12 months.

Comparison of paravalvular aortic leak characteristics in the Medtronic CoreValve versus Edwards Sapien Valve: Paravalvular aortic leak characteristics.

OBJECTIVES: Temporally quantify and localize paravalvular aortic leak (PVL) after transcatheter aortic valve replacement (TAVR) in the Medtronic CoreValve (MCV) versus the Edwards Sapien Valve (ESV). BACKGROUND: In order to increase the precision of THV selection and PVL intervention, an understanding of PVL characteristics is essential. METHODS: The frequency, severity, and location of post-TAVR PVL were evaluated with transthoracic echocardiography pre-discharge, one month, and one-year post-procedure in 202 patients receiving a MCV (N = 120) or ESV (N = 81). This was done through application of a clock face to the short axis of the aortic valve in order to divide the area into three tertiles. RESULTS: Pre-discharge differences between PVL frequency and severity in the MCV and ESV lost significance over time. Localizing these trends, MCV PVL frequency and severity significantly decreased in the first and third tertiles during most time periods while PVL in the second tertile of the MCV or in any of the tertiles of the ESV failed to improve. Presence of pre-discharge PVL was predictive of 30-day HF readmission and/or death (OR = 3.16, 95% CI: 0.99-10.12). Presence of pre-discharge and 30-day PVL was predictive of 1-year HF readmissions and/or death (OR = 2.12, 95% CI: 1.09-4.13 and OR = 1.99, 95% CI: 0.96-4.12). CONCLUSIONS: When comparing the MCV and ESV, not all locations of PVL improve equally over time, which has implications for heart failure readmissions. This could be used to influence valve selection and to identify cases in which earlier intervention on PVL may be appropriate.

Diagnostic time course, treatment, and in-hospital outcomes for patients with ST-segment elevation myocardial infarction presenting with nondiagnostic initial electrocardiogram: a report from the American Heart Association Mission: Lifeline program.

BACKGROUND: Prior studies indicate that a subset of patients diagnosed as having ST-segment elevation myocardial infarction (STEMI) will have an initial non-diagnostic electrocardiogram (ECG) during evaluation. However, the timing of diagnostic ECG changes in this group is unknown. Our primary aim was to describe the timing of ECG diagnosis of STEMI in patients whose initial ECG was non-diagnostic. Secondarily, we sought to compare the delivery of American College of Cardiology/American Heart Association guidelines-based care and in-hospital outcomes in this group compared with patients diagnosed as having STEMI on initial ECG. METHODS: We analyzed data from 41,560 patients diagnosed as having STEMI included in the National Cardiovascular Data Registry ACTION Registry-GWTG from January 2007 to December 2010. We divided this study population into 2 groups: those diagnosed on initial ECG (N = 36,994) and those with an initial non-diagnostic ECG that were diagnosed on a follow-up ECG (N = 4,566). RESULTS: In general, baseline characteristics and clinical presentations were similar between the 2 groups. For patients with an initial non-diagnostic ECG, 72.4% (n = 3,305) had an ECG diagnostic for STEMI within 90 minutes of their initial ECG. There did not appear to be significant differences in the administration of guideline-recommended treatments for STEMI, in-hospital major bleeding (P = .926), or death (P = .475) between these groups. CONCLUSIONS: In a national sample of patients diagnosed as having STEMI, 11.0% had an initial non-diagnostic ECG. Of those patients, 72.4% had a follow-up diagnostic ECG within 90 minutes of their initial ECG. There did not appear to be clinically meaningful differences in guidelines-based treatment or major inhospital outcomes between patients diagnosed as having STEMI on an initial ECG and those diagnosed on a follow-up ECG.

Echocardiography and EuroSCORE II for the stratification of low-gradient severe aortic stenosis and preserved left ventricular ejection fraction.

The purpose of this study was to explore the utility of echocardiography and the EuroSCORE II in stratifying patients with low-gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF ≥ 50%) with or without aortic valve intervention (AVI). The study included 323 patients with LG SAS (aortic valve area ≤ 1.0 cm2 and mean pressure gradient < 40 mmHg). Patients were divided into two groups: a high-risk group (EuroSCORE II ≥ 4%, n = 115) and a low-risk group (EuroSCORE II < 4%, n = 208). Echocardiographic and clinical characteristics were analyzed. All-cause mortality was used as a clinical outcome during mean follow-up of 2 ± 1.3 years. Two-year cumulative survival was significantly lower in the high-risk group than the low-risk patients (62.3% vs. 81.7%, p = 0.001). AVI tended to reduce mortality in the high-risk patients (70% vs. 59%; p = 0.065). It did not significantly reduce mortality in the low-risk patients (82.8% with AVI vs. 81.2%, p = 0.68). Multivariable analysis identified heart failure, renal dysfunction and stroke volume index (SVi) as independent predictors for mortality. The study suggested that individualization of AVI based on risk stratification could be considered in a patient with LG SAS and preserved LVEF.

Comparison of the Relation of Carotid Intima-Media Thickness With Incident Heart Failure With Reduced Versus Preserved Ejection Fraction (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Increased carotid intima-media thickness (cIMT) is associated with heart failure (HF) in previous studies, but it is not known whether the association of cIMT differs between HF with reduced (HFrEF) versus preserved ejection fraction (HFpEF). We studied 6699 participants (mean age 62 ± 10 years, 47% male, and 38% white) from the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline cIMT measurements. We classified HF events as HFrEF (EF <50%) or HFpEF (EF ≥ 50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios (HR), and 95% confidence intervals (CI) for the association between the IMT Z-score (measured maximum IMT of Internal Carotid (IC) and Common Carotid (CC) sites as the mean of the maximum IMT of the near and far walls of right and left sides), and incident HFrEF or HFpEF. Models were adjusted for covariates and interim coronary artery disease (CAD) events. A total of 191 HFrEF and 167 HFpEF events occurred during follow-up. In multivariable analysis, each 1 standard deviation increase in the measured maximum IMT (Z-score) was associated with both HFrEF and HFpEF in the unadjusted and demographically adjusted models [HR, 95% CI 1.57 (1.43 to 1.73)] and [HR, 95% CI 1.61 (1.47 to 1.77)] but not in the fully adjusted models [HR, 95% CI 1.11 (0.96 to 1.28)] and [HR, 95% CI 1.13 (0.98 to 1.30)]. In conclusion, cIMT was significantly associated with incident HF, but the association is partially attenuated with adjustment for demographic factors and becomes non-significant after adjustment for other traditional heart failure risk factors and interim CAD events. There was no difference in the association of IMT measures with HFrEF versus HFpEF.

Effect of fremanezumab on quality of life and productivity in patients with chronic migraine.

OBJECTIVE: To evaluate fremanezumab quarterly or monthly vs placebo on health-related quality of life, health status, patients' global impression of change, and productivity in patients with chronic migraine (CM). METHODS: HALO CM was a double-blind, placebo-controlled trial in patients with CM. Patients were randomized 1:1:1 to treatment with fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), fremanezumab monthly (225 mg at baseline, weeks 4 and 8), or placebo. This article assessed the effect of treatment with fremanezumab on health-related quality of life and productivity using the following prespecified assessments: the Migraine-Specific Quality of Life (MSQoL) questionnaire at baseline and weeks 4, 8, and 12; Patient Global Impression of Change (PGIC) questionnaire at weeks 4, 8, and 12; and EuroQoL 5-dimension, 5-response level (EQ-5D-5L) questionnaire and Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire at baseline and week 12. RESULTS: The full analysis set included 1,121 patients: 375 patients with quarterly dosing, 375 with monthly dosing, and 371 with placebo. Fremanezumab quarterly and monthly was associated with significant improvements over placebo in change from baseline mean scores in MSQoL domains (all, p < 0.05) to week 12. At week 12, fremanezumab also showed significant improvements in EQ-5D-5L visual analog scale (p < 0.05) and PGIC scores (p < 0.0001) as well as significant reductions from baseline in WPAI:GH scores (p < 0.01) and presenteeism (impairment while working; p < 0.05) vs placebo. CONCLUSIONS: Fremanezumab quarterly or monthly was associated with improvement over placebo in migraine-specific quality of life, overall health status, patients' global impression of change with treatment, and productivity in patients with CM. CLINICALTRIALSGOV IDENTIFIER: NCT02621931. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with CM, treatment with fremanezumab quarterly or monthly is associated with improvements in health-related quality of life and productivity.

Satisfaction and adherence with glatiramer acetate 40mg/mL TIW in RRMS after 12 months, and the effect of switching from 20mg/mL QD.

BACKGROUND: Patient satisfaction with treatment in relapsing-remitting multiple sclerosis (RRMS) has a direct impact on adherence to treatment and, consequently, upon treatment outcomes and costs. Patient-reported outcomes (PROs) are a common method for determining patient satisfaction in MS and other diseases. METHODS: The 12-month, open-label, Phase IV CONFIDENCE study assessed patient satisfaction and treatment adherence, using PROs, as well as safety outcomes in patients with RRMS treated with glatiramer acetate (GA). In the previously reported (Cutter et al., 2019) initial 6-month core phase of the study, patients were randomized to receive three-times-weekly (TIW) GA 40 mg/mL (GA40; n = 431) or once-daily GA 20 mg/mL (GA20; n = 430). In the 6-month, single-arm extension phase, 789 patients completing the core phase were treated with GA40 to determine whether benefits observed in the core phase were sustained during the extension phase, to ascertain if switching from GA20 to GA40 resulted in PRO changes, and to assess safety outcomes. RESULTS: Superior PRO scores for patient satisfaction with treatment, patient perception of treatment convenience, and symptomatic changes (fatigue impact and mental health) observed in the GA40 group versus the GA20 group in the core phase were all maintained in the extension phase. Treatment adherence, significantly greater in the GA40 versus the GA20 group in the core phase, was sustained in patients continuing to receive GA40 in the extension phase, while those who switched from GA20 to GA40 increased their adherence during the extension phase. Safety variables remained consistent throughout the study, with no notable changes observed in patients switching from GA20 to GA40. CONCLUSIONS: Data from the extension phase of the CONFIDENCE study show that the benefits associated with GA40 treatment in terms of medication satisfaction, treatment convenience perception, symptomatic changes in fatigue impact and mental health status, and treatment adherence were maintained over a 12-month observation period. These results confirm the preferential utility of GA40 versus GA20 in clinical practice, with no additional safety concerns associated with switching from GA20 to GA40.

Higher satisfaction and adherence with glatiramer acetate 40 mg/mL TIW vs 20 mg/mL QD in RRMS.

BACKGROUND: Patients who perceive their medication to be ineffective or inconvenient are less likely to be adherent to treatment, with potentially significant consequences on long-term clinical outcomes. Many patients with multiple sclerosis (MS) are nonadherent to treatment despite demonstrated efficacy of disease-modifying therapies (DMTs). While glatiramer acetate (GA; Copaxone®, Teva Pharmaceuticals) both 20 mg/mL once daily (GA20) and 40 mg/mL three times weekly (GA40) have demonstrated efficacy in relapsing-remitting MS (RRMS), GA40 has a superior tolerability profile in addition to a more convenient dosing schedule. These characteristics may give rise to greater treatment satisfaction and higher rates of adherence with potentially beneficial effects on clinical outcomes and health-related costs. METHODS: CONFIDENCE was a Phase 4, interventional, open-label, randomized, 2-arm, parallel-group, global study with a duration of 6 months. Patients (N = 861) were randomly assigned 1:1 to receive GA20 (n = 430) or GA40 (n = 431) during the core phase. The primary endpoint was patient-reported medication satisfaction using the Medication Satisfaction Questionnaire (MSQ). Secondary endpoints included self-reported convenience perception using the Treatment Satisfaction Questionnaire for Medication-9 convenience component, symptomatic changes (Modified Fatigue Impact Scale, MFIS), and Mental Health Inventory (MHI). Treatment adherence was measured by Multiple Sclerosis Treatment Adherence Questionnaire. Results from the core phase were included. RESULTS: During the core phase, 857 patients received treatments. Patients on GA40 were statistically significantly more satisfied with their medication than those on GA20 (LSM difference in MSQ, 0.3; 95% CI, 0.2, 0.5; p<0.001). Additionally, patients on GA40 found the treatment more convenient (p<0.001), were more adherent (p = 0.002), and reported statistically significant greater improvements in the MFIS Cognitive (p = 0.043) and the MHI Behavior Control (p = 0.014) subscales versus those on GA20. There were no new safety findings. CONCLUSIONS: Higher levels of satisfaction, perception of convenience, and adherence were reported by patients on GA40 than those on GA20. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered with ClinicalTrials.gov (NCT02499900).

Routine hematologic clinical tests as prognostic markers in patients with acute coronary syndromes.

Prognostic markers are needed to identify patients with acute coronary syndrome (ACS) who are at high risk for adverse events. Although the search for new biomarkers is quite active, prognostic information is available from routine hematologic tests, such as the complete blood count. For example, elevated white blood cell counts during ACS are associated with increased risk of mortality, heart failure, shock, and left ventricular dysfunction. Anemia is associated with increased risk of mortality, whereas elevated platelet counts predict poorer clinical and angiographic outcomes. In this review, we summarize the literature regarding the use of clinical hematology tests including white blood cell count, hemoglobin and hematocrit values, and platelet count as prognostic markers in patients with ACS, and we describe potential mechanisms to explain these associations.

Acute heart failure with preserved systolic function.

Many patients with acute heart failure have marked hypertension and preserved left ventricular ejection fraction. In these patients, the heart failure usually does not result from transient systolic dysfunction or valvular abnormalities but rather results from diastolic dysfunction. Treatment of this condition includes control of hypertension, cautious diuresis, and, if necessary, ventilatory support. Further workup after the acute phase should be directed by the overall clinical picture. Other potential contributing factors, such as renal artery stenosis, valvular heart disease, and ischemia, should be strongly considered. Unfortunately, chronic therapy for diastolic heart failure has not yet been standardized due to the paucity of clinical trial data. Strict control of hypertension appears to be of paramount importance. Angiotensin-converting enzyme inhibitors or receptor blockers may be of benefit in preventing repeat hospitalizations.

Incidence of coronary stent thrombosis based on academic research consortium definitions.

Stent thrombosis occurs infrequently after drug-eluting stent (DES) placement, but concerns have surfaced that identification of stent thrombosis based solely on angiography may underestimate the true incidence of this complication. The purpose of this study was to compare rates of stent thrombosis using Academic Research Consortium (ARC) definitions. From April 2002 to February 2005, bare-metal stents (BMSs) and DESs were placed at Wake Forest University Baptist Medical Center. Rates of ARC definite, probable, and possible stent thrombosis were evaluated. Overall, definite stent thrombosis occurred in 1.4% of BMSs and 1.1% of DESs (p = 0.47); probable stent thrombosis, in 1.0% of BMSs and 0.9% of DESs (p = 0.81); definite plus probable stent thrombosis, in 2.3% of BMSs and 1.9% of DESs (p = 0.48); and possible stent thrombosis, in 6.8% of BMSs and 3.5% of DESs (p <0.001). Rates of definite late (31 days to 1 year) and very late (>1 year) stent thrombosis were 0.9% for BMSs and 0.06% for DESs (p <0.001) and 0.16% for BMSs and 0.56% for DESs, respectively (p = 0.13). Rates of definite plus probable and late and very late stent thrombosis were 1.1% for BMSs and 0.19% for DESs (p <0.001) and 0.40% for BMSs and 0.68% for DESs, respectively (p = 0.31). Rates of possible stent thrombosis increased significantly for each thrombosis interval. In conclusion, rates of stent thrombosis using the proposed ARC definition differed by stent type, definition of stent thrombosis, and thrombosis interval. Use of the ARC probable stent thrombosis paralleled rates of definite stent thrombosis alone, but partially masked the occurrence of late (>1 year) stent thrombosis in DESs compared with BMSs.

Statin cost-effectiveness comparisons using real-world effectiveness data: formulary implications.

OBJECTIVE: To compare the effectiveness and cost-effectiveness among generic and branded statins in routine clinical practice. METHODS: Retrospective database study of patients, 18+, who were newly prescribed statin therapy. Statin effectiveness and cost-effectiveness in reducing low-density lipoprotein cholesterol (LDL-C) and attaining LDL-C goals were evaluated. RESULTS: Of 10,421 eligible patients, % LDL-C reduction was significantly greater (P < 0.001) with rosuvastatin (-31.6%) than other statins (-13.9 to -21.9%). Percentage of patients at moderate/high risk attaining LDL-C goal was higher (P < 0.001) for rosuvastatin (76.1%) versus other statins (57.6-72.6%). Rosuvastatin was more effective and less costly than atorvastatin. Among generic statins, simvastatin required >61% discount to branded price to achieve similar cost-effectiveness as generic lovastatin. CONCLUSIONS: In clinical practice, rosuvastatin is more effective and less costly in lowering LDL-C and LDL-C goal attainment compared with atorvastatin. Simvastatin was more cost-effective compared with lovastatin if >61% discount to branded price was achieved.

Retrospective Analysis of Healthcare Resource Use, Treatment Patterns, and Treatment-related Events in Patients with Huntington's Disease-associated Chorea Initiated on Tetrabenazine.

BACKGROUND: Huntington's disease (HD) is a multifaceted neurodegenerative disorder characterized by involuntary movements, specifically chorea, as well as behavioral and psychiatric disturbance, and cognitive dysfunction. Tetrabenazine was the first approved treatment for chorea, although tolerability concerns exist. OBJECTIVES: To characterize demographic and clinical characteristics of HD patients with chorea based on tetrabenazine use and examine treatment persistence with tetrabenazine in a real-world setting. METHODS: Patients with a claim for HD-associated chorea (ICD-9-CM code 333.4) between 1/1/08 and 9/30/15 were selected from the MarketScan® Commercial and Medicare Supplemental databases. The first diagnosis date during the study period was considered the index date, with ≥6 months of continuous medical and prescription coverage before and after the index date. Treatment persistence was defined as the number of days from initiation to discontinuation or end of follow-up period. Discontinuation was defined as a gap in therapy of ≥60 days. RESULTS: 1644 patients met selection criteria (mean age ± standard deviation: 54.5 ± 15.5), of which 151 (9.2%) were treated with tetrabenazine during the study period. The average (median) daily dose of tetrabenazine during the treatment period was 45.5 (42.3) mg/day. A total of 41.8% (59/141) of HD patients who initiated tetrabenazine experienced a ≥60-day gap in tetrabenazine therapy, with a median time to discontinuation of 293.5 days. During the 6-month post-index period after HD diagnosis, HD patients incurred higher all-cause healthcare costs ($20 204) vs the 6-month pre-index period ($6057), driven by higher hospitalization and pharmacy costs. CONCLUSIONS: A small percentage of HD patients with chorea were treated with tetrabenazine and discontinuation rates were high among those receiving treatment, with a median time to discontinuation of 9 months.