scholarly journals Strategies to reduce sample sizes in Alzheimer’s disease primary and secondary prevention trials using longitudinal amyloid PET imaging

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Isadora Lopes Alves ◽  
Fiona Heeman ◽  
Lyduine E. Collij ◽  
Gemma Salvadó ◽  
Nelleke Tolboom ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Secondary Prevention ◽  
Pet Imaging ◽  
Statistical Power ◽  
Amyloid Pet ◽  
Amyloid Burden ◽  
Sample Sizes ◽  
Primary And Secondary Prevention ◽  
Prevention Trials ◽  
Amyloid Pet Imaging

Abstract Background Detecting subtle-to-moderate biomarker changes such as those in amyloid PET imaging becomes increasingly relevant in the context of primary and secondary prevention of Alzheimer’s disease (AD). This work aimed to determine if and when distribution volume ratio (DVR; derived from dynamic imaging) and regional quantitative values could improve statistical power in AD prevention trials. Methods Baseline and annualized % change in [11C]PIB SUVR and DVR were computed for a global (cortical) and regional (early) composite from scans of 237 cognitively unimpaired subjects from the OASIS-3 database (www.oasis-brains.org). Bland-Altman and correlation analyses were used to assess the relationship between SUVR and DVR. General linear models and linear mixed effects models were used to determine effects of age, sex, and APOE-ε4 carriership on baseline and longitudinal amyloid burden. Finally, differences in statistical power of SUVR and DVR (cortical or early composite) were assessed considering three anti-amyloid trial scenarios: secondary prevention trials including subjects with (1) intermediate-to-high (Centiloid > 20.1), or (2) intermediate (20.1 < Centiloid ≤ 49.4) amyloid burden, and (3) a primary prevention trial focusing on subjects with low amyloid burden (Centiloid ≤ 20.1). Trial scenarios were set to detect 20% reduction in accumulation rates across the whole population and in APOE-ε4 carriers only. Results Although highly correlated to DVR (ρ = .96), cortical SUVR overestimated DVR cross-sectionally and in annual % change. In secondary prevention trials, DVR required 143 subjects per arm, compared with 176 for SUVR. Both restricting inclusion to individuals with intermediate amyloid burden levels or to APOE-ε4 carriers alone further reduced sample sizes. For primary prevention, SUVR required less subjects per arm (n = 855) compared with DVR (n = 1508) and the early composite also provided considerable sample size reductions (n = 855 to n = 509 for SUVR, n = 1508 to n = 734 for DVR). Conclusion Sample sizes in AD secondary prevention trials can be reduced by the acquisition of dynamic PET scans and/or by restricting inclusion to subjects with intermediate amyloid burden or to APOE-ε4 carriers only. Using a targeted early composite only leads to reductions of sample size requirements in primary prevention trials. These findings support strategies to enable smaller Proof-of-Concept Phase II clinical trials to better streamline drug development.

P5308Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease: Cochrane systematic review and meta-analysis of randomised clinical trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Stranges ◽  
A Takeda ◽  
N Martin ◽  
L Ellis ◽  
D Wijesekara ◽  
...  
Keyword(s):  
Risk Factors ◽  
Primary Prevention ◽  
Secondary Prevention ◽  
Total Mortality ◽  
Primary And Secondary Prevention ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Moderate Quality ◽  
Prevention Trials ◽  
Quality Evidence

Abstract Background Observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on cardiovascular disease (CVD) but the randomised controlled trial (RCT) evidence is limited. Objective To determine the effectiveness of a Mediterranean-style diet for the primary and secondary prevention of CVD. Methods We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Web of Science, DARE, HTA, NHS EED and trial registers (September 2018). We selected RCTs in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). Both of the following key components were required for our definition of a Mediterranean-style diet: high monounsaturated/saturated fat ratio and a high intake of plant based foods, including fruits, vegetables, and legumes. The intervention could be dietary advice, provision of relevant foods or both. The comparison group received either no intervention, minimal intervention, usual care or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow-up periods of 3 months or more. Results Overall, 30 RCTs (12,461 participants randomised) and 7 ongoing trials met our inclusion criteria, whereas 22 primary prevention trials and 6 secondary prevention trials were analysed. Low quality evidence shows little or no effect of the PREDIMED (7747 randomised) intervention (advice to follow a Mediterranean diet plus supplemental extra virgin olive oil or tree nuts) compared to a low fat diet on CVD mortality (HR 0.81 (95% CI 0.5, 1.32)) or total mortality (HR 1.0 (95% CI 0.81, 1.24)) over 4.8 years. There was however a reduction in the number of strokes with the PREDIMED intervention (HR 0.6 (95% CI 0.45, 0.8), moderate quality evidence). For secondary prevention, in the Lyon Diet Heart Study (605 CVD patients), there was moderate quality evidence of a reduction in CVD mortality (HR 0.35 (95% CI 0.15, 0.82)) and total mortality (HR 0.44 (95% CI 0.21, 0.92)) with the intervention, over 46 months. For CVD risk factors, in primary prevention trials, there was low quality evidence for a possible small reduction in total cholesterol (−0.16 mmol/L (95% CI −0.32, 0.00), and moderate quality evidence for a reduction in SBP (−2.99 mmHg (95% CI −3.45, −2.53)) and DBP (−2.0 mmHg (95% CI −2.29, −1.71)). In secondary prevention trials, there was moderate quality evidence of no effect of a Mediterranean-style diet on lipid levels and low or very low quality evidence for blood pressure. Conclusions Despite the relatively large number of studies included in this review, there is still some uncertainty regarding the effects of a Mediterranean-style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention. The ongoing studies may provide more certainty in the future.

P1-188: Enrichment strategies for secondary prevention trials: The effect of restrictive inclusion criteria on statistical power and sample size

2008 ◽  
Vol 4 ◽  
pp. T263-T264
Author(s):  
Steven D. Edland ◽  
Linda K. McEvoy ◽  
Dominic Holland ◽  
John C. Roddey ◽  
Christine Fennema-Notestine ◽  
...  
Keyword(s):  
Secondary Prevention ◽  
Sample Size ◽  
Statistical Power ◽  
Inclusion Criteria ◽  
Prevention Trials

P2-325: AMYLOID PET IMAGING IN A COMMUNITY NEUROLOGY PRACTICE: FEASIBILITY AND CLINICAL OUTCOMES

2006 ◽  
Vol 14 (7S_Part_15) ◽  
pp. P807-P807
Author(s):  
Michael H. Rosenbloom ◽  
Kathryn A. Wyman-Chick ◽  
Lauren O. Erickson ◽  
Paul Carolan ◽  
Joshua Johnson ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Pet Imaging ◽  
Amyloid Pet ◽  
Amyloid Pet Imaging

scholarly journals Patient and Caregiver Assessment of the Benefits From the Clinical Use of Amyloid PET Imaging

2018 ◽  
Vol 32 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Rafid Mustafa ◽  
Jared R. Brosch ◽  
Gil D. Rabinovici ◽  
Bradford C. Dickerson ◽  
Maria C. Carrillo ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Amyloid Pet ◽  
Clinical Use ◽  
Amyloid Pet Imaging

scholarly journals A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in Clinical Practice

2018 ◽  
Vol 46 (3-4) ◽  
pp. 154-167 ◽  
Author(s):  
Yejin Kim ◽  
Paul Rosenberg ◽  
Esther Oh
Keyword(s):  
Positron Emission Tomography ◽  
Clinical Practice ◽  
Pet Imaging ◽  
Clinical Utility ◽  
Patient Management ◽  
Emission Tomography ◽  
Amyloid Pet ◽  
Diagnostic Confidence ◽  
Positron Emission ◽  
Amyloid Pet Imaging

Background: Molecular imaging of brain amyloid for the diagnosis of Alzheimer’s disease (AD) using positron emission tomography (PET) has been approved for use in clinical practice by the Food and Drug Administration (FDA) since 2012. However, the clinical utility and diagnostic impact of amyloid PET imaging remain controversial. We conducted a review of the recent studies investigating clinical utility of amyloid PET imaging with focus on changes in diagnosis, diagnostic confidence, and patient management. Summary: A total of 16 studies were included in the final analysis. Overall rate of changes in diagnosis after amyloid PET ranged from 9 to 68% (pooled estimate of 31%, 95% CI 23–39%). All studies reported overall increase in diagnostic confidence or diagnostic certainty after amyloid PET. Changes in patient management ranged from 37 to 87%; the most common type of change in management reported was either the initiation or discontinuation of planned AD medications. Key Messages: Amyloid PET imaging led to moderate to significant changes in diagnosis, diagnostic confidence, and subsequent patient management. It may be most useful in patients with high level of diagnostic uncertainty even after the completing the standard workup.

Abstract 14575: Implantable Cardiac Defibrillator in the Setting of Tetralogy of Fallot: Long-Term Follow-Up of a French National Multicenter Retrospective Registry

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Abdeslam Bouzeman ◽  
Maxime De Guillebon ◽  
Guillaume Duthoit ◽  
Magalie Ladouceur ◽  
Raphael Martins ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ventricular Tachycardia ◽  
Primary Prevention ◽  
Secondary Prevention ◽  
Tetralogy Of Fallot ◽  
Primary And Secondary Prevention ◽  
Long Term Follow Up ◽  
Appropriate Therapy

Background: Tetralogy of Fallot (TOF) is the most frequent form of congenital heart disease managed by EP physicians for potential ICD. However, few studies have reported long-term outcomes of TOF patients with ICD. Methods: Between 2005 and 2014, all TOF patients with ICD in 17 French centers were enrolled in a specific evaluation aiming to determine characteristics at implantation as well as outcomes (overall mortality, appropriate ICD therapies, and device-related complications). Results: Overall 78 patients (45±13 years, 64% males) were enrolled. A majority of patients were implanted in the setting of secondary prevention (73%), whereas the remaining (27%) in primary prevention. Among the latest group, known risk factors for sudden cardiac death were: severe pulmonary regurgitation (30%,) prior palliative shunt (50%), syncope with unknown origin (25%), inducible ventricular tachycardia (45%), QRS duration ≥180ms (18%), non-sustained ventricular tachycardia (25%), and documented sustained supra ventricular tachycardia (45%).Overall, patients implanted in the setting of primary prevention presented with a mean of 3.1±1.4 risk factors. After a mean follow-up of 4.9±3.8 years, 35 patients (45%) experienced at least one appropriate therapy (25% in the primary prevention group compared to 53% in the secondary prevention group), giving annual-incidences of 6.9% (95%CI 0.14-13.7) and 21.3% (12.4-30.3) respectively (P=0,01). The mean time between ICD implantation and the first appropriate therapy was 2.2±3.2 years, without significant differences between primary and secondary prevention. Overall, ≥one ICD-related complication occurred in 30 patients (38%), including inappropriate shock (n=9), major pocket hematoma (n=1), lead dysfunction (n=12), infection (n=4), shoulder algodystrophia (n=2), device failure or dislodgement needing reintervention (n=2). Eventually, four patients were transplanted (5%), and six patients (8%) died during the course of follow-up. Conclusions: Considering relatively long-term follow-up, patients with TOF and ICDs experience high rates of appropriate ICD therapies, in both primary and secondary prevention. Major ICD-related complications remain, however, high.

454 ASSOCIATION BETWEEN STATINS AND MAJOR ADVERSE CARDIAC EVENTS AMONG OLDER ADULTS WITH FRAILTY: A SYSTEMATIC REVIEW

2021 ◽  
Vol 50 (Supplement_2) ◽  
pp. ii5-ii7
Author(s):  
M Hale ◽  
H Zaman ◽  
D Mehdizadeh ◽  
O Todd ◽  
H Callaghan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Primary Prevention ◽  
Secondary Prevention ◽  
Randomised Trial ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Major Adverse Cardiovascular Events ◽  
Primary And Secondary Prevention ◽  
Cardiac Events

Abstract Background Statins reduce the risk of major adverse cardiovascular events (MACE), however, their clinical benefit for primary and secondary prevention among older adults with frailty is uncertain. This review investigates whether statins prescribed for primary and secondary prevention are associated with reduced MACE among adults aged ≥65 years with frailty. Methods Systematic review of studies published between 01.01.1952 and 01.01.2019 in MEDLINE, Embase, Scopus, Web of Science, Cochrane Library and the International Pharmaceutical Abstracts. Studies that investigated the effect of statins on MACE among adults ≥65 years with a validated frailty assessment were included. Data were extracted from the papers as per a pre-published protocol, PROSPERO: CRD42019127486. Risk of bias was assessed using the Cochrane Risk of Bias in non-randomised studies of interventions. Finding 18794 abstracts were identified for screening. From these, six cohort studies fulfilled the inclusion criteria. There were no randomised clinical trials. Of studies involving statins for primary and secondary prevention (n = 6), one found statins were associated with reduced mortality (hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.37–0.93) and another found they were not (p = 0.73). One study of statins used for secondary prevention found they were associated with reduced mortality (HR 0.28, 95%CI 0.21–0.39). No studies investigated the effect of statins for primary prevention or the effect of statins on the frequency of MACE. Discussion This review summarizes the existing available evidence for decision making for statin prescribing for older adults with frailty. This study identified only observational evidence that, among older people with frailty, statins are associated with reduced mortality when prescribed for secondary prevention, and an absence of evidence evaluating statin therapy for primary prevention. The findings of this study highlight that randomised trial data are urgently needed to better inform the use of statins among older adults living with frailty.

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