scholarly journals Relationship Between Change in Serum Uric Acid and Ischemic Stroke in Chinese Hypertensive Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Qiu-hong Tan ◽  
Lin Liu ◽  
Yu-qing Huang ◽  
Yu-ling Yu ◽  
Jia-yi Huang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Ischemic Stroke ◽  
Serum Uric Acid ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Elevated Risk ◽  
Rank Test ◽  
Hypertensive Patients ◽  
Cox Proportional Hazards Models ◽  
The Relationship

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients.Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity.Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 μmol/L; middle (SUA stable): ≥-32.6 μmol/L, <40.2 μmol/L; high (SUA increase substantially): ≥40.2 μmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially.Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

U-Shaped Association of Serum Uric Acid With All-Cause and Cause-Specific Mortality in US Adults: A Cohort Study

2019 ◽  
Vol 105 (3) ◽  
pp. e597-e609 ◽  
Author(s):  
Lihua Hu ◽  
Guiping Hu ◽  
Benjamin Ping Xu ◽  
Lingjuan Zhu ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Uric Acid ◽  
Cohort Study ◽  
Serum Uric Acid ◽  
Inflection Point ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Specific Mortality ◽  
The Relationship

Abstract Background In addition to the controversy regarding the association of hyperuricemia with mortality, uncertainty also remains regarding the association between low serum uric acid (SUA) and mortality. We aimed to assess the relationship between SUA and all-cause and cause-specific mortality. Methods This cohort study included 9118 US adults from the National Health and Nutrition Examination Survey (1999-2002). Multivariable Cox proportional hazards models were used to evaluate the relationship between SUA and mortality. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and 2-piecewise Cox proportional hazards models, to address the nonlinearity between SUA and mortality. Results During a median follow-up of 5.83 years, 448 all-cause deaths occurred, with 100 cardiovascular disease (CVD) deaths, 118 cancer deaths, and 37 respiratory disease deaths. Compared with the reference group, there was an increased risk of all-cause, CVD, cancer, and respiratory disease mortality for participants in the first and third tertiles of SUA. We further found a nonlinear and U-shaped association between SUA and mortality. The inflection point for the curve was found at a SUA level of 5.7 mg/dL. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.80 (0.65-0.97) and 1.24 (1.10-1.40) to the left and right of the inflection point, respectively. This U-shaped association was observed in both sexes; the inflection point for SUA was 6 mg/dL in males and 4 mg/dL in females. Conclusion Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, supporting a U-shaped association between SUA and mortality.

scholarly journals Prospective Study of Serum Uric Acid Levels and First Stroke Events in Chinese Adults With Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Hu ◽  
Longlong Hu ◽  
Rihua Yu ◽  
Fengyu Han ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Proportional Hazards ◽  
Survival Curve ◽  
Cox Proportional Hazards ◽  
Chinese Adults ◽  
Stroke Event ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
The Relationship

Objectives: We investigated the association between serum uric acid (SUA) levels and the risk of the first stroke in Chinese adults with hypertension.Methods: A total of 11, 841 hypertensive patients were selected from the Chinese Hypertension Registry for analysis. The relationship between SUA levels and first stroke was determined using multivariable Cox proportional hazards regression, smoothing curve fitting, and Kaplan–Meier survival curve analysis.Results: During a median follow-up of 614 days, 99 cases of the first stroke were occurred. Cox proportional hazards models indicated that SUA levels were not significantly associated with the first stroke event [adjusted-hazard ratio (HR) per SD increase: 0.98, 95% CI 0.76–1.26, P = 0.889]. In comparison to the group without hyperuricemia (HUA), there were no significantly higher risks of first stroke events (adjusted-HR: 1.22, 95% CI 0.79–1.90, P = 0.373) in the population with HUA. However, in the population less than 60 years old, subjects with HUA had a significantly higher risk of the first stroke than the population without HUA (adjusted-HR: 4.89, 95% CI 1.36–17.63, P = 0.015). In subjects older than 60 years, we did not find a significant relationship between HUA and first stroke (adjusted-HR: 0.97, 95% CI 0.60–1.56, P = 0.886). Survival analysis further confirmed this discrepancy (log-rank P = 0.013 or 0.899 for non-aging or aging group).Conclusion: No significant evidence in the present study indicated that increased SUA levels were associated with the risk of first stroke in the Chinese adults with hypertension. Age played an interactive role in the relationship between HUA and the first stroke event.

Abstract P005: Comparative Effectiveness of Rivaroxaban versus Warfarin for the Treatment of Patients with Non-valvular Atrial Fibrillation

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Faye L Norby ◽  
Lindsay G Bengtson ◽  
Lin Y Chen ◽  
Richard F MacLehose ◽  
Pamela L Lutsey ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Real World ◽  
Proportional Hazards ◽  
Large Population ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Gi Bleeding ◽  
Cox Proportional Hazards Models ◽  
The Us

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.

Abstract T MP48: Androgen Suppression in Patients with Prostate Cancer Increases Incidence of Combined Cardiovascular Outcomes

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Zuber S Ali ◽  
Danielle M Greere ◽  
Robyn L Shearer ◽  
Syed Ali Gardezi ◽  
Arshad Jahangir
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Age Groups ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Cardiovascular Outcomes ◽  
Elevated Risk ◽  
Disease Stage ◽  
Cox Proportional Hazards Models ◽  
Androgen Suppression

Introduction: Androgen suppression therapy for prostate cancer is controversial due to adverse fatal and non-fatal cardiovascular outcomes reported in some studies. However, effects of androgen suppression on stroke have not been fully assessed in the elderly. Methods: Patients diagnosed with prostate cancer during 2007-2013 in a large community-based healthcare system were identified from the Cancer Registry, electronic records, and billing codes. Those who underwent androgen suppression therapy with Gonadotropin-releasing hormone agonist (GnRH) were propensity-matched to patients treated without androgen suppression therapy by age at cancer diagnosis, race/ethnicity, disease stage and outcome, body mass index and use of surgery, radiation, and chemotherapy. Tests of independence and Cox proportional hazards models were used to examine effects of hormone therapy on acute myocardial infarction (AMI), stroke, and mortality outcomes. Models also adjusted for patient comorbidities. Results: A total of 1282 patients and 641 matched-pairs were identified, with mean diagnosis age of 69 yr and follow-up period of 3.05 yr. Effects of androgen suppression therapy on AMI (P=0.051) and stroke (P=0.062) were of marginal to non-significance, but adjusted-odds of death and combined AMI, stroke, and death were 1.61 times (P=0.002; odds ratio [OR] 95% CI: 1.19-2.18) and 1.70 times (P<0.001; OR 95% CI: 1.26-2.28) greater, respectively, for men with than without androgen suppression. An interaction of androgen suppression and age-group (<65 yr, 65-74 yr, >74 yr) was discovered for combined outcomes, suggesting increased probability of AMI, stroke, and/or death with age (8.6-20.0%; P=0.003) for patients without androgen suppression but elevated risk of outcomes across all age groups (18.3-22.4%; P=0.546) for men treated with androgen suppression therapy. Conclusion: Endogenous androgen suppression presents elevated risk of combined cardiovascular and death outcomes, especially for men <65 yr.

Association of circulating tumor cells (CTC) with survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a real-world cohort.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 59-59
Author(s):  
Umang Swami ◽  
Taylor Ryan McFarland ◽  
Benjamin Haaland ◽  
Adam Kessel ◽  
Roberto Nussenzveig ◽  
...  
Keyword(s):  
Real World ◽  
Proportional Hazards ◽  
De Novo ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Cox Proportional Hazards Models ◽  
Risk Of Progression ◽  
The Relationship

59 Background: In mCSPC, baseline CTC counts have been shown to correlate with PSA responses and progression free survival (PFS) in small studies in the context of androgen deprivation therapy (ADT) without modern intensification with docetaxel or novel hormonal therapy. Similar correlation of CTC count with PSA responses and PFS was recently reported from an ongoing phase 3 trial in mCSPC setting (SWOG1216) without reporting the association in the context of ADT intensification. Furthermore, none of these studies correlated CTCs with overall survival (OS). Herein we evaluated whether CTCs were associated with outcomes including OS in a real world mCPSC population treated with intensified as well as non-intensified ADT. Methods: Eligibility criteria: new mCSPC receiving ADT with or without intensification and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. The relationship between CTC counts (categorized as: 0, 1-4, and ≥5/7.5 ml) and both PFS and OS was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason, PSA at ADT initiation, de novo vs. non-de novo status, and ADT intensification vs. non-intensification therapy. Results: Overall 99 pts were identified. Baseline characteristics are summarized in Table. In unadjusted analyses, CTC counts of ≥5 as compared to 0 were strongly associated with inferior PFS (hazard ratio [HR] 3.38, 95% CI 1.85-6.18; p < 0.001) and OS (HR 4.44 95% CI 1.63-12.10; p = 0.004). In multivariate analyses, CTC counts of ≥5 as compared to 0 continued to be associated with inferior PFS (HR 5.49, 95% CI 2.64-11.43; p < 0.001) and OS (HR 4.00, 95% CI 1.31-12.23; p = 0.015). Within the ADT intensification subgroup also, high CTC counts were associated with poor PFS and OS. For PFS, the univariate HR for CTC ≥5 vs. 0 was 4.87 (95% CI 1.66-14.30; p = 0.004) and multivariate HR for CTC ≥5 vs. 0 was 7.43 (95% CI 1.92-28.82; p = 0.004). For OS, the univariate HR for CTC ≥5 vs. 0 was 15.88 (95% CI 1.93-130.58; p = 0.010) and multivariate HR for CTC ≥5 vs. 0 was 24.86 (95% CI 2.03-304.45; p = 0.012). Conclusions: To best of our knowledge this is the first study to show that high baseline CTC counts are strongly associated with inferior PFS as well as OS in pts with newly diagnosed mCSPC, even in those who received intensified ADT therapy. Identifying these pts at highest risk of progression and death can help with counselling and prognostication in clinics as well as design and enrollment in future clinical trials. [Table: see text]

scholarly journals Eosinophil count and mortality risk in incident hemodialysis patients

2020 ◽  
Vol 35 (6) ◽  
pp. 1032-1042
Author(s):  
Duk-Hee Kang ◽  
Yuji Lee ◽  
Carola Ellen Kleine ◽  
Yong Kyu Lee ◽  
Christina Park ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Eosinophil Count ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Time Varying ◽  
Cox Proportional Hazards Models ◽  
Lower Baseline ◽  
All Cause Mortality ◽  
Relationship Of ◽  
The Relationship

Abstract Background Eosinophils are traditionally known as moderators of allergic reactions; however, they have now emerged as one of the principal immune-regulating cells as well as predictors of vascular disease and mortality in the general population. Although eosinophilia has been demonstrated in hemodialysis (HD) patients, associations of eosinophil count (EOC) and its changes with mortality in HD patients are still unknown. Methods In 107 506 incident HD patients treated by a large dialysis organization during 2007–11, we examined the relationships of baseline and time-varying EOC and its changes (ΔEOC) over the first 3 months with all-cause mortality using Cox proportional hazards models with three levels of hierarchical adjustment. Results Baseline median EOC was 231 (interquartile range 155–339) cells/μL and eosinophilia (&gt;350 cells/μL) was observed in 23.4% of patients. There was a gradual increase in EOC over time after HD initiation with a median ΔEOC of 5.1 (IQR −53–199) cells/μL, which did not parallel the changes in white blood cell count. In fully adjusted models, mortality risk was highest in subjects with lower baseline and time-varying EOC (&lt;100 cells/μL) and was also slightly higher in patients with higher levels (≥550 cells/μL), resulting in a reverse J-shaped relationship. The relationship of ΔEOC with all-cause mortality risk was also a reverse J-shape where both an increase and decrease exhibited a higher mortality risk. Conclusions Both lower and higher EOCs and changes in EOC over the first 3 months after HD initiation were associated with higher all-cause mortality in incident HD patients.

scholarly journals Baseline Serum Bilirubin and Risk of First Stroke in Hypertensive Patients

2020 ◽  
Vol 9 (12) ◽  
Author(s):  
Jiancheng Wang ◽  
Xianglin Zhang ◽  
Zhuxian Zhang ◽  
Yuanyuan Zhang ◽  
Jingping Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Proportional Hazards ◽  
Total Bilirubin ◽  
Serum Bilirubin ◽  
Cox Proportional Hazards ◽  
Direct Bilirubin ◽  
Serum Total Bilirubin ◽  
Inverse Association ◽  
Baseline Serum ◽  
Hypertensive Patients

Background Data on the association between serum bilirubin and the risk of stroke are limited and inconclusive. We aimed to evaluate the association between serum bilirubin and the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods and Results Our study was a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). A total of 19 906 hypertensive patients were included in the final analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of first stroke associated with serum bilirubin levels. The median follow‐up period was 4.5 years. When serum total bilirubin was assessed as tertiles, the adjusted HR of first ischemic stroke for participants in tertile 3 (12.9–34.1 μmol/L) was 0.75 (95% CI, 0.59–0.96), compared with participants in tertile 1 (<9.3 μmol/L). When direct bilirubin was assessed as tertiles, a significantly lower risk of first ischemic stroke was also found in participants in tertile 3 (2.5–24.8 μmol/L) (adjusted HR, 0.77; 95% CI, 0.60–0.98), compared with those in tertile 1 (<1.6 μmol/L). However, there was no significant association between serum total bilirubin (tertile 3 versus 1: adjusted HR, 1.45; 95% CI, 0.89–2.35) or direct bilirubin (tertile 3 versus 1: adjusted HR, 1.27; 95% CI, 0.76–2.11) and first hemorrhagic stroke. Conclusions In this sample of Chinese hypertensive patients, there was a significant inverse association between serum total bilirubin or direct bilirubin and the risk of first ischemic stroke.

scholarly journals Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001015 ◽  
Author(s):  
Fernando Pérez Ruiz ◽  
Pascal Richette ◽  
Austin G Stack ◽  
Ravichandra Karra Gurunath ◽  
Ma Jesus García de Yébenes ◽  
...  
Keyword(s):  
Uric Acid ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
First Year ◽  
Cox Proportional Hazards Models ◽  
Crude Mortality ◽  
Risk Patients ◽  
The Impact ◽  
Related Mortality

ObjectiveTo determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.MethodsProspective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.ResultsOf 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).ConclusionsFailure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.

Is more aggressive lymph node assessment associated with improved survival in stage II-III colorectal cancer? Evidence from the Surveillance, Epidemiology and End Results (SEER) cancer registry

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4048-4048
Author(s):  
Y. Yeh ◽  
Q. Cai ◽  
J. Chao ◽  
M. Russell
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Stage Ii ◽  
Rank Test ◽  
Stage Iiia ◽  
Nccn Guidelines ◽  
Cox Proportional Hazards Models

4048 Background: NCCN guidelines recommend assessment of =12 lymph nodes (LN) to improve accuracy in colorectal cancer (CRC) staging. Previous studies have used various cut-points to assess the relationship between the number of LN sampled and survival. The association between NCCN guideline-compliant nodal sampling and survival is assessed, while controlling for other risk factors. Methods: We selected 145,485 adult patients newly diagnosed with stage II or III from SEER during 1990–2003. Kaplan-Meier curves were compared using the log-rank test. Cox proportional hazards models were constructed to determine the effect of sampling ≥ 12 LN on survival. Results: Median patient follow-up was 5.7 years. The table shows overall survival rates in CRC patients with < 12 versus =12 LN assessed: After adjusting for age, sex, tumor size and grade, sampling ≥ 12 LN was independently associated with improved survival. For patients with =12 versus <12 LN assessed, survival increased by 13% for stage IIa [HR=0.75; 95%CI 0.72–0.78; p< .001], 16% for stage IIb [HR=0.69; 95%CI 0.67- 0.71; p< .001], 12% for stage IIIb [HR=0.75; 95%CI 0.72–0.77], and 10% for stage IIIc [HR=0.85, 95%CI 0.81–0.89]. The association was not statistically significant for stage IIIa patients. Conclusion: Consistent with previous reports, this analysis found that optimal nodal sampling increased survival across stage II and III, specifically when ≥ 12 LN are sampled and when controlling for other risk factors. Furthermore, the results underscore the need for adhering to the NCCN guidelines. The lack of a statistically significant association in stage IIIa patients may be due to small cohort size. [Table: see text] [Table: see text]

Adherence and cumulative bisphosphonate dose in relation to risk of skeletal-related events among older patients with multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18250-e18250
Author(s):  
Jifang Zhou ◽  
Karen Sweiss ◽  
Pritesh Rajni Patel ◽  
Edith Nutescu ◽  
Naomi Ko ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cumulative Dose ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Competing Risk ◽  
Rank Test ◽  
Subdistribution Hazard ◽  
Cox Proportional Hazards Models ◽  
Utilization Patterns ◽  
Skeletal Related Events

e18250 Background: Adjuvant intravenous bisphosphonates (IV BP) reduce the risk of skeletal-related events (SRE) in patients with multiple myeloma (MM). We examined the effects of bisphosphonate utilization patterns (adherence, cumulative dose and frequency) on risk of SRE. Methods: Patients aged 65 years or older and diagnosed with first primary MM between 2001 and 2011 were identified using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Patients receiving at least one dose of IV BP after MM diagnosis were identified and 5-year SRE-free survival was estimated using the Kaplan-Meier method stratified by demographic groups and compared with the log rank test. Cox proportional hazards models were fit to determine the association between IV BP utilization patterns and SRE after propensity score matching. We investigated the outcome of multiple recurrent SRE using the approach of Andersen-Gill, and estimated subdistribution hazard ratios (SHR) and 95% confidence intervals for risk of first SRE, accounting for death as competing risk. Results: The final cohort included 9176 MM patients with a median age of 76 years. The adjusted 5-year competing-risk SRE model showed a 48% reduction in risk of SRE (95% CI 0.49-0.55) with use of IV BP. In multivariable analyses taking into account competing risks, greater adherence to IV BP, higher cumulative IV BP dose and more frequent administration were all associated with a statistically significant reduction in SRE risks (See Table). Conclusions: Use of IV BP in patients with MM was associated with significant reduction in SRE risk over the 5-year period after MM diagnosis. The effectiveness of IV BP therapy was greater with increasing cumulative dose, adherence to and greater frequency of IV BP administration. [Table: see text]

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