Competing risk analysis in a large cardiovascular clinical trial: An <scp>APEX</scp> substudy

Arbetter, Douglas; Jain, Purva; Yee, Megan K.; Michalak, Nathan; Hernandez, Adrian F.; Hull, Russell D.; Goldhaber, Samuel Z.; Harrington, Robert A.; Gold, Alex; Cohen, Alexander T.; Gibson, C. Michael

doi:10.1002/pst.1823

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…A competing risk is an event whose occurrence precludes the critical event of interest. Competing risk analysis is time-to-event analysis that considers all kinds of fatal or non-fatal events which potentially alter or prevent subjects from experiencing the interest endpoint (14,15). Thus, when predicting the incidence of the outcome of disease, competing risk analysis can provide a more accurate and less biased estimate for clinicians to make individual therapy strategies (16).…”

Section: Introductionmentioning

confidence: 99%

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis

Wu¹,

Chen²,

Chen³

et al. 2019

J. Thorac. Dis

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Background: Many factors are reported to be related to the prognosis of patients with esophageal adenocarcinoma (EAC), but few reliable and straightforward tools for clinicians to estimate individual mortalities have been developed. This study aimed to evaluate the probability of cancer-specific death for patients with EAC and to build nomograms for predicting long-term cancer-specific mortality and overall mortality for EAC patients. Methods: Between 2004 and 2013, a total of 20,623 patients were identified from the surveillance, epidemiology, and end results (SEER) database and randomly divided into training (N=14,436) and validation (N=6,187) cohorts. The cumulative incidence functions (CIFs) of EAC-specific death and other causes were evaluated at the 1st, 3rd, and 5th year after diagnosis. We integrated the significant prognostic factors to construct nomograms and subjected them to internal and external validation. Results: The CIFs of EAC-specific survival at 1, 3, and 5 years after diagnosis were 60.9%, 37.1%, and 31.3%, respectively. Predictors for cancer-specific mortality for EAC comprised tumor grade, tumor extension, the involvement of lymph nodes, distant metastasis, surgery of primary site, insurance recode, and marital status. For overall mortality, it also included the predictor of age at diagnosis. The nomograms were well-calibrated and had good discriminative ability with concordance indexes (c-indexes) of 0.733, 0.728, and 0.728 for 1-, 3-and 5-year prognosis prediction of EAC-specific mortality respectively, and 0.726, 0.720, 0.719 for 1-, 3-, and 5-year prognosis prediction of overall mortality respectively. Conclusions: We proposed and validated the effective and convenient nomograms to predict cancerspecific mortality and the overall mortality for patients with EAC, which only require the basic information available in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis

Wu¹,

Chen²,

Chen³

et al. 2019

J. Thorac. Dis

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“…We calculated the incidence rates per 1000 person-years of the three study outcomes in the two groups. After confirming the assumption of proportional hazards by plotting the graph of the survival function versus the survival time and the graph of the log (-log(survival)) versus the log of survival time, we applied the Cox proportional hazard model to examine the association of clarithromycin with overall mortality and cardiovascular mortality after adjustments for age by year, sex, comorbidities, CCI, the number of medical visits, and 10 confounding drugs, and applied competing risk analysis [ 32 ] to examine the association of clarithromycin with cardiovascular morbidity. Moreover, we calculated each patient's cumulative defined daily dose (cDDD) of clarithromycin recommended by the WHO [ 33 ] to address the dose–response relationship of clarithromycin with study outcomes, given the usual daily dose of clarithromycin is 1 g and isometric increase in cDDD is 2000.…”

Section: Methodsmentioning

confidence: 99%

A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer disease

Chen

Yu³

et al. 2022

BMC Gastroenterol

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Background Clarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD). Methods This nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD–PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed. Results Clarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93–1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57–1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89–1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant. Conclusion Concerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

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“…The baseline differences between clarithromycin users and non-users were compared using t -tests for continuous variables and the chi-squared test for categorical variables. Death before cardiovascular morbidity was considered a competing risk event ( 39 ). After confirming the assumption of proportional hazards by plotting survival function vs. survival time, and log (-log (survival)) vs. log of survival time, we applied the modified Cox proportional hazard model in the presence of competing risk to examine the association of clarithromycin with cardiovascular morbidity and individual event from heart, stroke, and PAOD, and the Cox proportional hazard model to examine the association of clarithromycin with mortality, with adjustment for all covariates (age per year, sex, comorbidities, number of medical visits, and confounding drugs).…”

Section: Methodsmentioning

confidence: 99%

No dose-response relationship of clarithromycin utilization on cardiovascular outcomes in patients with stable coronary heart disease: Analysis of Taiwan’s national health insurance claims data

Yu¹,

Chen²,

Li³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundClarithromycin is widely used to treat various bacterial infections and has been reported to have potential cardiovascular risk. However, it is uncertain whether this association was dose dependent and confounded by indication bias in patients with stable coronary heart disease (CHD).MethodsThis cohort study retrospectively analyzed a national health insurance claims data from Taiwan’s 2005 Longitudinal Generation Tracking Database. We used a new-user design and 1:1 propensity score matching. A total of 9,631 eligible clarithromycin users and 9,631 non-users in 2004–2015 were subject to final analysis. All patients were followed-up after receiving clarithromycin or on the matched corresponding date until occurrence of cardiovascular morbidity in the presence of competing mortality, all-cause and cause-specific mortality, or through the end of 2015. The effect of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes were also addressed.ResultsClarithromycin use, compared with non-use, was associated with higher risk for all-cause [adjusted hazard ratios (aHR), 1.43; 95% confidence interval, 1.29–1.58], cardiovascular (1.35; 1.09–1.67), and non-cardiovascular (1.45; 1.29–1.63) mortality, but not for overall cardiovascular morbidity. Further analysis of individual cardiovascular morbidity demonstrated major risk for heart events (1.25; 1.04–1.51) in clarithromycin users than non-users. However, there was no relationship of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes. Analyses of the effects over time showed that clarithromycin increased cardiovascular morbidity (1.21; 1.01–1.45), especially heart events (1.39; 1.10–1.45), all-cause (1.57; 1.38–1.80), cardiovascular (1.58; 1.20–2.08), and non-cardiovascular (1.57; 1.35–1.83) mortality during the first 3 years. Thereafter, clarithromycin effect on all outcomes almost dissipated.ConclusionClarithromycin use was associated with increased risk for short-term cardiovascular morbidity (especially, heart events) and mortality without a dose-response relationship in patients with stable CHD, which was not dose dependent and confounded by indications. Hence, patients with stable CHD while receiving clarithromycin should watch for these short-term potential risks.

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Competing risk analysis in a large cardiovascular clinical trial: An APEX substudy

Cited by 9 publications

References 20 publications

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis

A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer disease

No dose-response relationship of clarithromycin utilization on cardiovascular outcomes in patients with stable coronary heart disease: Analysis of Taiwan’s national health insurance claims data

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