scholarly journals Time in range in relation to all-cause and cardiovascular mortality in patients with type 2 diabetes: a prospective cohort study

2020 ◽  
Author(s):  
Jingyi Lu ◽  
Chunfang Wang ◽  
Yun Shen ◽  
Lei Chen ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Proportional Hazards ◽  
Reference Group ◽  
Surrogate Marker ◽  
Cox Proportional Hazards ◽  
Increased Risk ◽  
Time In Range ◽  
Different Levels ◽  
Cvd Mortality

<b>Objective: </b>There is growing evidence linking time in range (TIR), an emerging metric for assessing glycemic control, to diabetes-related outcomes. We aimed to investigate the association between TIR and mortality in patients with type 2 diabetes. <p><b>Research design and methods: </b>A total of 6225 adult patients with type 2 diabetes were included from January 2005 to December 2015 from a single center in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline, and the participants were stratified into 4 groups by TIR: >85%, 71-85%, 51-70%, and ≤50%. Cox proportional hazards regression models were used to estimate the association between different levels of TIR and the risks of all-cause and cardiovascular disease (CVD) mortality.</p> <p><b>Results: </b>The mean age of the participants was 61.7 years at baseline. During a median follow-up of 6.9 years, 838 deaths were identified, 287 of which were due to CVD. The multivariable-adjusted hazard ratios associated with different levels of TIR (>85% [reference group], 71-85%, 51-70%, and ≤50%) were 1.00, 1.23 (95% CI, 0.98-1.55), 1.30 (95% CI, 1.04-1.63), and 1.83 (95% CI, 1.48-2.28) for all-cause mortality (P for trend <0.001), and 1.00, 1.35 (95% CI, 0.90-2.04), 1.47 (95% CI, 0.99-2.19), and 1.85 (95% CI, 1.25-2.72) for CVD mortality (P for trend =0.015), respectively. </p> <p><b>Conclusions: </b>The present study indicated an association of lower TIR with an increased risk of all-cause and CVD mortality among patients with type 2 diabetes, supporting the validity of TIR as a surrogate marker of long-term adverse clinical outcomes.<b></b></p> <p> </p>

scholarly journals Time in range in relation to all-cause and cardiovascular mortality in patients with type 2 diabetes: a prospective cohort study

2020 ◽  
Author(s):  
Jingyi Lu ◽  
Chunfang Wang ◽  
Yun Shen ◽  
Lei Chen ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Proportional Hazards ◽  
Reference Group ◽  
Surrogate Marker ◽  
Cox Proportional Hazards ◽  
Increased Risk ◽  
Time In Range ◽  
Different Levels ◽  
Cvd Mortality

<b>Objective: </b>There is growing evidence linking time in range (TIR), an emerging metric for assessing glycemic control, to diabetes-related outcomes. We aimed to investigate the association between TIR and mortality in patients with type 2 diabetes. <p><b>Research design and methods: </b>A total of 6225 adult patients with type 2 diabetes were included from January 2005 to December 2015 from a single center in Shanghai, China. TIR was measured with continuous glucose monitoring at baseline, and the participants were stratified into 4 groups by TIR: >85%, 71-85%, 51-70%, and ≤50%. Cox proportional hazards regression models were used to estimate the association between different levels of TIR and the risks of all-cause and cardiovascular disease (CVD) mortality.</p> <p><b>Results: </b>The mean age of the participants was 61.7 years at baseline. During a median follow-up of 6.9 years, 838 deaths were identified, 287 of which were due to CVD. The multivariable-adjusted hazard ratios associated with different levels of TIR (>85% [reference group], 71-85%, 51-70%, and ≤50%) were 1.00, 1.23 (95% CI, 0.98-1.55), 1.30 (95% CI, 1.04-1.63), and 1.83 (95% CI, 1.48-2.28) for all-cause mortality (P for trend <0.001), and 1.00, 1.35 (95% CI, 0.90-2.04), 1.47 (95% CI, 0.99-2.19), and 1.85 (95% CI, 1.25-2.72) for CVD mortality (P for trend =0.015), respectively. </p> <p><b>Conclusions: </b>The present study indicated an association of lower TIR with an increased risk of all-cause and CVD mortality among patients with type 2 diabetes, supporting the validity of TIR as a surrogate marker of long-term adverse clinical outcomes.<b></b></p> <p> </p>

scholarly journals Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality

2020 ◽  
Vol 105 (9) ◽  
pp. 3005-3014
Author(s):  
Brittany R Lapin ◽  
Kevin M Pantalone ◽  
Alex Milinovich ◽  
Shannon Morrison ◽  
Andrew Schuster ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Proportional Hazards ◽  
Negative Binomial ◽  
Cox Proportional Hazards ◽  
Vascular Events ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
History Of ◽  
Mortality Hazard Ratio

Abstract Purpose Type 2 diabetes–related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P). Methods A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016. Using an electronic algorithm, patients were classified as no DPN, DPN + P, or DPN-P. Primary outcomes included number of vascular events and time to mortality. Independent associations with DPN + P were evaluated using multivariable negative binomial and Cox proportional hazards regression models, adjusting for demographics, socioeconomic characteristics, and comorbidities. Results Of 43 945 patients with type 2 diabetes (age 64.6 ± 14.0 years; 52.1% female), 13 910 (31.7%) had DPN: 9104 DPN + P (65.4%) vs 4806 DPN-P (34.6%). Vascular events occurred in 4538 (15.1%) of no DPN patients, 2401 (26.4%) DPN + P, and 1006 (20.9%) DPN-P. After adjustment, DPN + P remained a significant predictor of number of vascular events (incidence rate ratio [IRR] = 1.55, 95% CI, 1.29-1.85), whereas no DPN was protective (IRR = 0.70, 95% CI, 0.60-0.82), as compared to DPN-P. Compared to DPN-P, DPN + P was also a significant predictor of mortality (hazard ratio = 1.42, 95% CI, 1.25-1.61). Conclusions Our study found a significant association between pain in DPN and an increased risk of vascular events and mortality. This observation warrants longitudinal study of the risk factors and natural history of pain in DPN.

scholarly journals Levels of ankle–brachial index and the risk of diabetes mellitus complications

2020 ◽  
Vol 8 (1) ◽  
pp. e000977
Author(s):  
Lia Alves-Cabratosa ◽  
Marc Comas-Cufí ◽  
Anna Ponjoan ◽  
Maria Garcia-Gil ◽  
Ruth Martí-Lluch ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Proportional Hazards ◽  
Microvascular Complications ◽  
Ankle Brachial Index ◽  
Cardiovascular Prevention ◽  
Cox Proportional Hazards ◽  
Cox Models ◽  
Complications Of Diabetes ◽  
Increased Risk

ObjectiveWe sought to compare the association of categorized ankle–brachial index (ABI) with mortality and complications of diabetes in persons with no symptoms of peripheral arterial disease (PAD) and in primary cardiovascular disease prevention.Research design and methodsThis is a retrospective cohort study of persons with type 2 diabetes aged 35–85 years, from 2006 to 2011. Data were obtained from the Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAPQ). Participants had an ABI measurement that was classified into six categories. For each category of ABI, we assessed the incidence of mortality; macrovascular complications of diabetes: acute myocardial infarction (AMI), ischemic stroke, and a composite of these two; and microvascular complications of this metabolic condition: nephropathy, retinopathy, and neuropathy. We also estimated the HRs for these outcomes by ABI category using Cox proportional hazards models.ResultsData from 34 689 persons with type 2 diabetes were included. The mean age was 66.2; 51.5% were men; and the median follow-up was 6.0 years. The outcome with the highest incidence was nephropathy, with 24.4 cases per 1000 person-years in the reference category of 1.1≤ABI≤1.3. The incidences in this category for mortality and AMI were 15.4 and 4.1, respectively. In the Cox models, low ABI was associated with increased risk and was significant from ABI lower than 0.9; below this level, the risk kept increasing steeply. High ABI (over 1.3) was also associated with significant increased risk for most outcomes.ConclusionsThe studied categories of ABI were associated with different risks of type 2 diabetes complications in persons asymptomatic for PAD, who were in primary cardiovascular prevention. These findings could be useful to optimize preventive interventions according to the ABI category in this population.

scholarly journals Anemia and incidence of dementia in patients with new-onset type 2 diabetes: a nationwide population-based cohort study

2020 ◽  
Vol 8 (1) ◽  
pp. e001289
Author(s):  
Jae Woo Choi ◽  
Tae Hyun Kim ◽  
Euna Han
Keyword(s):  
Type 2 Diabetes ◽  
Proportional Hazards ◽  
Population Based ◽  
Primary Diagnosis ◽  
Cox Proportional Hazards ◽  
Onset Type ◽  
Increased Risk ◽  
New Onset ◽  
Incidence Of Dementia

IntroductionThis study aimed to examine the association between anemia and the incidence of dementia in patients with new-onset type 2 diabetes.Research design and methodsThis study used the Korean National Health Insurance Service-Health Screening Cohort and included 32 590 participants aged ≥40 years who were diagnosed with new-onset type 2 diabetes between 2004 and 2007 and followed up until 2013. Anemia was defined according to the criteria provided by the WHO, hemoglobin <120 g/L for women and <130 g/L for men, and was measured from after diagnosis date of type 2 diabetes to 2007. Dementia was defined by the Classification of Diseases 10th revision code as primary diagnosis and was measured from after hemoglobin measurement to 2013. We calculated the adjusted HR (AHR) and 95% CI to assess the risk of dementia using multivariable Cox proportional hazards regression models.ResultsWe identified 1682 patients who developed dementia within a 7.5-year follow-up. Among patients with type 2 diabetes, patients with anemia were associated with an increased risk of dementia than those without anemia (AHR, 1.21; 95% CI 1.06 to 1.39). Patients with mild (AHR, 1.18; 95% CI 1.03 to 1.38) and moderate (AHR, 1.39; 95% CI 1.06 to 1.83) anemia were associated with an increased risk of dementia than those without anemia among patients with type 2 diabetes. Men (AHR, 1.47; 95% CI 1.16 to 1.83) and middle-aged adults (AHR, 1.31; 95% CI 1.03 to 1.75) with anemia were associated with an increased risk of dementia than their counterparts without anemia among patients with type 2 diabetes.ConclusionsOur findings suggest that anemia is significantly associated with an increased risk of dementia among patients with newly diagnosed type 2 diabetes.

scholarly journals Risk of a post-colonoscopy colorectal cancer in patients with type 2 diabetes: a Danish population-based cohort study

2021 ◽  
Vol 8 (1) ◽  
pp. e000786
Author(s):  
Frederikke Schønfeldt Troelsen ◽  
Henrik Toft Sørensen ◽  
Lars Pedersen ◽  
Rune Erichsen
Keyword(s):  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Cohort Study ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Increased Risk ◽  
First Time

ObjectivePrevalent type 2 diabetes (T2D) is associated with an increased risk of colorectal cancer and could impair the quality of bowel preparation for colonoscopy. This may in turn increase the risk of overlooked precancerous polyps and subsequent risk of post-colonoscopy colorectal cancer (PCCRC). We investigated whether patients with T2D are at increased risk of PCCRC compared with patients without T2D.DesignWe conducted a population-based cohort study of patients with T2D and without T2D undergoing colonoscopy in Denmark (1995–2015). We investigated the risk of PCCRC by calculating >6 to 36 months cumulative incidence proportions (CIPs) treating death and colectomy as competing risks. Using Cox proportional-hazards regression analyses, we also computed HRs of PCCRC, comparing patients with T2D and non-T2D. According to the World Endoscopy Organization guidelines, we calculated PCCRC 3-year rates to estimate the proportions of T2D and non-T2D CRC patients experiencing PCCRC.ResultsWe identified 29 031 patients with T2D and 333 232 patients without T2D undergoing colonoscopy. We observed 250 PCCRCs among patients with T2D and 1658 PCCRCs among patients without T2D. The >6 to 36 months CIP after a first-time colonoscopy was 0.64% (95% CI 0.55% to 0.74%) for T2D and 0.36% (95% CI 0.34% to 0.38%) for patients without T2D. The HRs of PCCRC were 1.43 (95% CI 1.21 to 1.72) after a first-time colonoscopy and 1.18 (95% CI 0.75 to 1.85) after a second-time colonoscopy. The PCCRC 3-year rate was 7.9% for patients with T2D and 7.4% for patients without T2D.ConclusionT2D may be associated with an increased HR of PCCRC.

scholarly journals Prenatal diethylstilbestrol exposure and risk of diabetes, gallbladder disease, and pancreatic disorders and malignancies

2020 ◽  
pp. 1-8
Author(s):  
Rebecca Troisi ◽  
Marianne Hyer ◽  
Linda Titus ◽  
Julie R. Palmer ◽  
Elizabeth E. Hatch ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pancreatic Cancer ◽  
General Population ◽  
Proportional Hazards ◽  
Gallbladder Disease ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Increased Risk ◽  
Pancreatic Disorders

Abstract Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6–51 and HR = 7.0, 95% CI 1.5–33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88–1.5) or diabetes (HR = 1.1, 95% CI 0.9–1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84–20) or general population (SIR: 1.9, 95% CI 1.0–3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.

scholarly journals Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study

2021 ◽  
Vol 9 (2) ◽  
pp. e002352
Author(s):  
Ingrid Hougen ◽  
Reid H Whitlock ◽  
Paul Komenda ◽  
Claudio Rigatto ◽  
Kristin K Clemens ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Real World ◽  
Cardiovascular Events ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Dipeptidyl Peptidase 4 ◽  
Increased Risk ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
All Cause Mortality

IntroductionMetformin is the initial oral antihyperglycemic agent (OHA) of choice for most patients with type 2 diabetes (T2D). However, more than one agent is often required for optimal glucose control. As the choice of preferred second OHAs is less well defined, we sought to compare the real-world safety of sulfonylureas to other OHAs as add-on therapy to metformin in patients with T2D.Research design and methodsThis retrospective cohort study included adults in Manitoba, Canada with T2D from 2006 to 2017. Using a new-user design, we divided patients who started on metformin into two groups: add-on therapy with a sulfonylurea and add-on therapy with a different OHA. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. We calculated propensity scores and applied inverse probability of treatment weights to each individual. We compared groups using Cox proportional hazards regression and explored differences in HRs between pre-2008 (acarbose, meglitinides, and thiazolidinediones) and post-2008 (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose linked transporter-2 inhibitors) OHAs.ResultsOur cohort included 32 576 individuals (28 077 metformin plus sulfonylurea and 4499 metformin plus ‘other’). Patients newly prescribed a sulfonylurea in the setting of metformin had a higher risk of all-cause mortality (HR 1.44, 95% CI 1.12 to 1.84, p=0.005) and major hypoglycemic episodes (HR 2.78, 95% CI 1.66 to 4.66, p<0.001) than those prescribed an ‘other’ OHA. No differences in cardiovascular events were observed (HR 0.99, 95% CI 0.81 to 1.22, p=0.92). In subgroup analyses, mortality and cardiovascular event risk was higher in patients prescribed sulfonylureas versus post-2008 OHAs.ConclusionsSulfonylureas as add-on therapy to metformin are associated with increased risk of all-cause mortality and major hypoglycemic episodes compared with ‘other’ OHAs. Post hoc analysis suggests newer OHAs may be preferred to sulfonylureas as second-line therapy for glycemic control.

scholarly journals Association Between Change in Accelerometer-Measured and Self-Reported Physical Activity and Cardiovascular Disease in the Look AHEAD Trial

2022 ◽  
Author(s):  
John M. Jakicic ◽  
Robert I. Berkowitz ◽  
Paula Bolin ◽  
George A. Bray ◽  
Jeanne M. Clark ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Self Report ◽  
Look Ahead ◽  
The Look

OBJECTIVE: To conduct <i>post-hoc</i> secondary analysis examining the association between change in physical activity (PA), measured with self-report and accelerometry, from baseline to 1 and 4 years and cardiovascular disease (CVD) outcomes in the Look AHEAD Trial. <p>RESEARCH DESIGN AND METHODS: Participants were adults with overweight/obesity and type 2 diabetes with PA data at baseline and year 1 or 4 (n = 1,978). Participants were randomized to diabetes support and education or intensive lifestyle intervention. Measures included accelerometry-measured moderate-to-vigorous PA (MVPA), self-reported PA, and composite (morbidity and mortality) CVD outcomes.</p> <p>RESULTS: In pooled analyses of all participants, using Cox proportional hazards models, each 100 MET-min/wk increase in accelerometry-measured MVPA from baseline to 4 years was associated with decreased risk of the subsequent primary composite outcome of CVD. Results were consistent for changes in total MVPA [HR=0.97 (95% CI: 0.95, 0.99)] and MVPA accumulated in <u>></u>10-minute bouts [HR=0.95 (95% CI: 0.91, 0.98)], with a similar pattern for secondary CVD outcomes. Change in accelerometry-measured MVPA at 1 year and self-reported change in PA at 1 and 4 years were not associated with CVD outcomes.</p> <p>CONCLUSIONS: Increased accelerometry-measured MVPA from baseline to year 4 is associated with decreased risk of CVD outcomes. This suggests the need for long-term engagement in MVPA to reduce the risk of CVD in adults with overweight/obesity and type 2 diabetes.</p>

scholarly journals Associations of Diet Quality and All-Cause Mortality Across Levels of Cardiometabolic Health and Disease: A 7.6-Year Prospective Analysis From the Dutch Lifelines Cohort

2021 ◽  
Author(s):  
Petra C Vinke ◽  
Gerjan Navis ◽  
Daan Kromhout ◽  
Eva Corpeleijn
Keyword(s):  
Type 2 Diabetes ◽  
Diet Quality ◽  
Total Population ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Dietary Guidelines ◽  
Cardiometabolic Health ◽  
Ageing Population ◽  
All Cause Mortality

<b>Objective: </b>To simultaneously investigate the association of diet quality and all-cause mortality in groups with varying cardiometabolic diseases (CMDs) at baseline.<br><p> <b>Design:</b> From the population-based Lifelines cohort, 40,892 non-underweight participants aged ≥50 years with data on diet quality and confounding factors were included (enrollment 2006-2013). From food frequency questionnaire data, tertiles of the Lifelines diet score were calculated (T1 = poorest, T3 = best diet quality). Four CMD categories were defined: 1) CMD-free, 2) type 2 diabetes, 3) one cardiovascular disease (CVD), 4) two or more CMDs. Months when deaths occurred were obtained from municipal registries up until November 2019. Multivariable Cox proportional hazards models were applied for the total population and stratified by CMD categories.<br> <b>Results</b>: After a median follow-up of 7.6 years, 1,438 participants died. Diet quality and CMD categories were independently associated with all-cause mortality in crude and adjusted models (p < 0.001). A dose-response relationship of diet quality with all-cause mortality was observed in the total population (P for trend < 0.001, T2 vs. T3 = 1.22 (1.07-1.41), T1 vs. T3 = 1.57 (1.37-1.80)). In stratified analyses, the association was significant for CMD-free individuals (T1 vs. T3 = 1.63 (1.38-1.93)) and for type 2 diabetes patients (1.87 (1.17-3.00)), but not for patients with one CVD (1.39 (0.93-2.08)) or multiple CMDs (1.19 (0.80-1.76)).<br> <b>Conclusions</b>: A high-quality diet can potentially lower all-cause mortality risk in the majority of the ageing population. Its effect may be greatest for CMD-free individuals and patients with type 2 diabetes. Tailored dietary guidelines may be required for patients with extensive histories of CMDs. </p>

Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 94-94
Author(s):  
Maha H. A. Hussain ◽  
Cora N. Sternberg ◽  
Eleni Efstathiou ◽  
Karim Fizazi ◽  
Qi Shen ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Reference Group ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Analysis Model ◽  
Increased Risk ◽  
Psa Nadir ◽  
Post Hoc

94 Background: The PROSPER trial demonstrated prolonged MFS and OS for men with nmCRPC and rapidly rising PSA treated with ENZA vs placebo, both in combination with androgen deprivation therapy (ADT). The final survival analysis of PROSPER (Sternberg et al. NEJM 2020) recently reported a median OS of 67.0 months (95% CI, 64.0 to not reached) with ENZA and 56.3 months (95% CI, 54.4 to 63.0) with placebo (hazard ratio [HR] for death, 0.73; 95% CI, 0.61 to 0.89; P = .001). Post hoc analyses of PROSPER evaluating PSA dynamics have demonstrated longer MFS with greater PSA decline (Hussain et al. ESMO Sept 19-21, 2020. Poster 685P) and increased risk of metastases in patients with even modest PSA progression vs those without (Saad et al. Eur Urol 2020). Here we further explored the relationship between PSA dynamics and outcomes in PROSPER using uniquely defined PSA subgroups of decline. Methods: Eligible men in PROSPER had nmCRPC, a PSA level ≥ 2 ng/mL at baseline, and a PSA doubling time ≤ 10 months. Men continued ADT, were randomized 2:1 to ENZA 160 mg once daily vs placebo, and had PSA evaluation at week 17 and every 16 weeks thereafter. This post hoc analysis evaluated OS and MFS for 4 mutually exclusive subgroups defined by PSA nadir using men with PSA reduction < 50% as the reference group. The HR is based on an unstratified Cox proportional hazards analysis model. Results: 1401 men were enrolled in PROSPER; 933 were treated with ENZA and PSA data were available for 905. Measured at nadir, 38% of these men achieved PSA reduction ≥ 90% (actual nadir < 0.2 ng/mL), and another 27% achieved PSA reduction ≥ 90% (actual nadir ≥ 0.2 ng/mL). Among men in the placebo arm of PROSPER only 3/457 reported PSA reduction ≥ 90%. Median OS and MFS increased with increasing depth of PSA decline (Table). Conclusions: In men with nmCRPC and rapidly rising PSA treated with ADT plus ENZA, there was a close relationship between the degree of PSA decline and survival outcomes. Defining PSA by both percent decline and actual decline below 0.2 ng/mL revealed a previously under-appreciated relationship between these PSA metrics and highlights the importance of PSA nadir as an intermediate biomarker in nmCRPC. Clinical trial information: NCT02003924. [Table: see text]

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