INCREASED RISK OF ADVERSE CARDIOVASCULAR EVENTS ASSOCIATED WITH IBRUTINIB USE IN CHRONIC LYMPHOCYTIC LEUKEMIA: A PROPENSITY-MATCHED POPULATION-BASED COHORT STUDY

Objective Several studies have shown an increased risk for cardiovascular disease (CVD) in hyperthyroidism, but most studies have been too small to address the effect of hyperthyroidism on individual cardiovascular endpoints. Our main aim was to assess the association among hyperthyroidism, acute cardiovascular events and mortality. Design It is a nationwide population-based cohort study. Data were obtained from the Danish Civil Registration System and the Danish National Patient Registry, which covers all Danish hospitals. We compared the rate of all-cause mortality as well as venous thromboembolism (VTE), acute myocardial infarction (AMI), ischemic and non-ischemic stroke, arterial embolism, atrial fibrillation (AF) and percutaneous coronary intervention (PCI) in the two cohorts. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated. Results The study included 85 856 hyperthyroid patients and 847 057 matched population-based controls. Mean follow-up time was 9.2 years. The HR for mortality was highest in the first 3 months after diagnosis of hyperthyroidism: 4.62, 95% CI: 4.40–4.85, and remained elevated during long-term follow-up (>3 years) (HR: 1.35, 95% CI: 1.33–1.37). The risk for all examined cardiovascular events was increased, with the highest risk in the first 3 months after hyperthyroidism diagnosis. The 3-month post-diagnosis risk was highest for atrial fibrillation (HR: 7.32, 95% CI: 6.58–8.14) and arterial embolism (HR: 6.08, 95% CI: 4.30–8.61), but the risks of VTE, AMI, ischemic and non-ischemic stroke and PCI were increased also 2- to 3-fold. Conclusions We found an increased risk for all-cause mortality and acute cardiovascular events in patients with hyperthyroidism.

Download Full-text

Risk of malignancy associated with chronic lymphocytic leukemia: A population based Canadian study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20020 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20020-20020

Author(s):

M. W. Pitz ◽

V. Banerji ◽

A. A. Demers ◽

Z. Nugent ◽

J. Strutinsky-Mason ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Cancer Registry ◽

Population Based ◽

Lymphocytic Leukemia ◽

Increased Risk ◽

Risk Of Malignancy ◽

Synchronous Malignancies ◽

Adjusted Incidence ◽

Mean Time

20020 Background: Patients with Chronic Lymphocytic Leukemia (CLL) may have an increased risk of other malignancies. Available literature reports on malignancies that develop after the diagnosis of CLL, but does not discuss malignancies that precede the diagnosis of CLL. Methods: All patients diagnosed with CLL between 01/1998 and 12/2003 were extracted from the provincial cancer registry and a centralized flow cytometry database. All other malignancies were obtained from the cancer registry. Dates of diagnoses were compared. A malignancy within 30 days before or after the diagnosis of CLL was considered synchronous with that diagnosis. Results were compared with the age-adjusted incidence of cancer in the province, excluding CLL. Results: Of the 713 cases of CLL, 333 invasive cancers and 38 in situ neoplasia were identified before, synchronous to, or after the diagnosis of CLL. Synchronous malignancies occurred in 4% of cases. The Standardized Incidence Ratio (SIR) for other malignancy subsequent to CLL was 1.40 (95% confidence interval [CI] 1.09–1.80) derived from 65 tumors for males, and 1.29 (95% CI 0.90–1.80) from 35 tumors for females. Mean time to diagnosis of subsequent cancer was 2.0 years (standard deviation[SD] 1.5). The SIR for other malignancy in the 5 years preceding the diagnosis of CLL was 1.36 (95% CI 0.93–1.94) from 31 tumors for males and 0.77 (95% CI 0.54–1.08) from 35 tumors for females. Mean time from diagnosis of preceding malignancy to CLL was 9.4 years (SD 8.7). Conclusions: In this population based study, patients with CLL are at increased risk of other invasive and in situ cancers. This risk is apparent after but not before the diagnosis of CLL, particularly in males. The mechanism of this increased risk may be acquired with the presence of CLL through an underlying but undetermined mechanism, as opposed to an inherent or more longstanding predisposition to malignancy. No significant financial relationships to disclose.

Download Full-text

Overall and Cancer-Specific Survival of Patients With Breast, Colon, Kidney, and Lung Cancers With and Without Chronic Lymphocytic Leukemia: A SEER Population-Based Study

Journal of Clinical Oncology ◽

10.1200/jco.2012.43.4449 ◽

2013 ◽

Vol 31 (7) ◽

pp. 930-937 ◽

Cited By ~ 35

Author(s):

Benjamin M. Solomon ◽

Kari G. Rabe ◽

Susan L. Slager ◽

Jerry D. Brewer ◽

James R. Cerhan ◽

...

Keyword(s):

Breast Cancer ◽

Chronic Lymphocytic Leukemia ◽

Population Based ◽

Lymphocytic Leukemia ◽

Disease Stage ◽

Tumor Type ◽

Cancer Specific Survival ◽

Lung Cancers ◽

Increased Risk ◽

A Site

Purpose Chronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the disease course of these cancers once they occur. Patients and Methods All patients with cancers of the breast (n = 579,164), colorectum (n = 412,366), prostate (n = 631,616), lung (n = 489,053), kidney (n = 95,795), pancreas (n = 82,116), and ovary (n = 61,937) reported to the SEER program from 1990 to 2007 were identified. Overall survival (OS; death resulting from any cause) and cancer-specific survival were examined, comparing patients with and without pre-existing CLL. Cancer-specific survival was evaluated for each tumor type in a site-specific manner (eg, death resulting from breast cancer in a patient with breast cancer). Results Patients with cancers of the breast (hazard ratio [HR], 1.70; P < .001), colorectum (HR, 1.65; P < .001), kidney (HR, 1.54; P < .001), prostate (HR, 1.92; P < .001), or lung (HR, 1.19; P < .001) had inferior OS if they had a pre-existing diagnosis of CLL after adjusting for age, sex, race, and disease stage. These results for OS remained significant for patients with cancers of the breast, colorectum, and prostate after excluding or censoring CLL-related deaths. Cancer-specific survival was also inferior for patients with cancers of the breast (HR, 1.41; P = .005) and colorectum (HR, 1.46; P < .001) who had pre-existing CLL after adjusting for age, sex, race, and disease stage. Conclusion Inferior OS and cancer-specific survival was observed for several common cancers in patients with pre-existing CLL. Additional studies are needed to determine the optimal management of these malignancies in patients with CLL and whether more aggressive screening or alternative approaches to adjuvant therapy are needed.

Download Full-text

Cardiovascular Risk Associated With Ibrutinib Use in Chronic Lymphocytic Leukemia: A Population-Based Cohort Study

Journal of Clinical Oncology ◽

10.1200/jco.21.00693 ◽

2021 ◽

pp. JCO.21.00693

Author(s):

Husam Abdel-Qadir ◽

Nasruddin Sabrie ◽

Darryl Leong ◽

Andrea Pang ◽

Peter C. Austin ◽

...

Keyword(s):

Health Care ◽

Cohort Study ◽

Chronic Lymphocytic Leukemia ◽

Index Date ◽

Population Based ◽

Lymphocytic Leukemia ◽

Administrative Databases ◽

Time Varying ◽

Significant Difference ◽

Ischemic Events

PURPOSE Ibrutinib reduces mortality in chronic lymphocytic leukemia (CLL). It increases the risk of atrial fibrillation (AF) and bleeding and there are concerns about heart failure (HF) and central nervous system ischemic events. The magnitude of these risks remains poorly quantified. METHODS Using linked administrative databases, we conducted a population-based cohort study of Ontario patients who were treated for CLL diagnosed between 2007 and 2019. We matched ibrutinib-treated patients with controls treated with chemotherapy but unexposed to ibrutinib on prior AF, age ≥ 66 years, anticoagulant exposure, and propensity for receiving ibrutinib. Study outcomes were AF-related health care contact, hospital-diagnosed bleeding, new diagnoses of HF, and hospitalizations for stroke and acute myocardial infarction (AMI). The cumulative incidence function was used to estimate absolute risks. We used cause-specific regression to study the association of ibrutinib with bleeding rates, while adjusting for anticoagulation as a time-varying covariate. RESULTS We matched 778 pairs of ibrutinib-treated and unexposed patients with CLL (N = 1,556). The 3-year incidence of AF-related health care contact was 22.7% (95% CI, 19.0 to 26.6) in ibrutinib-treated patients and 11.7% (95% CI, 9.0 to 14.8) in controls. The 3-year risk of hospital-diagnosed bleeding was 8.8% (95% CI, 6.5 to 11.7) in ibrutinib-treated patients and 3.1% (95% CI, 1.9 to 4.6) in controls. Ibrutinib-treated patients were more likely to start anticoagulation after the index date. After adjusting for anticoagulation as a time-varying covariate, ibrutinib remained positively associated with bleeding (HR, 2.58; 95% CI, 1.76 to 3.78). The 3-year risk of HF was 7.7% (95% CI, 5.4 to 10.6%) in ibrutinib-treated patients and 3.6% (95% CI, 2.2 to 5.4) in controls. There was no significant difference in the risk of ischemic stroke or AMI. CONCLUSION Ibrutinib is associated with higher risk of AF, bleeding, and HF, but not AMI or stroke.

Download Full-text

Increased risk of cardiovascular events in end-stage renal disease patients with osteoporosis: a nationwide population-based cohort study

Osteoporosis International ◽

10.1007/s00198-014-2982-0 ◽

2014 ◽

Vol 26 (2) ◽

pp. 785-793 ◽

Cited By ~ 2

Author(s):

T.-M. Yu ◽

C.-L. Lin ◽

K.-H. Shu ◽

Y.-L. Liu ◽

C.-H. Chen ◽

...

Keyword(s):

Cohort Study ◽

Renal Disease ◽

End Stage Renal Disease ◽

Cardiovascular Events ◽

Population Based ◽

Increased Risk ◽

Stage Renal Disease ◽

End Stage

Download Full-text

Overall and cancer-specific survival of breast, colon, and lung cancer in patients with and without chronic lymphocytic leukemia: A SEER population-based study of over 1 million patients.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6571 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6571-6571

Author(s):

Benjamin Maurice Solomon ◽

Kari G. Rabe ◽

Susan L Slager ◽

Jerry D Brewer ◽

James R. Cerhan ◽

...

Keyword(s):

Lung Cancer ◽

Chronic Lymphocytic Leukemia ◽

Population Based ◽

Lymphocytic Leukemia ◽

Cancer Site ◽

Cancer Specific Survival ◽

Hazard Ratios ◽

Increased Risk ◽

History Of ◽

Age And Sex

6571 Background: Chronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the natural history of these cancers once they occur. Methods: All patients with breast (n=583,838), colon (n=412,932), prostate (n=632,922), lung (n=489,290), kidney (n=95,902), pancreas (n=82,121) and ovarian (n=61,958) cancer reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1990 to 2007 were identified. Overall survival (OS; death due to any cause) and cancer-specific survival (death due to cancer site of interest) were examined, comparing patients with or without pre-existing CLL. Age- and sex-adjusted hazard ratios (HRs) were calculated. Results: OS for patients with pre-existing CLL was inferior for patients with breast (HR=1.61; p<0.001), colon (HR=1.65; p<0.001), kidney (HR=1.41; p<0.001), prostate (HR=1.75; p<0.001), and lung (HR=1.22; p<0.001) cancer after adjusting for age and sex. After excluding CLL-related deaths, OS remained shorter among patients with breast (p<0.001), colon (p<0.001), kidney (p=0.03), prostate (p<0.001), and lung (p<0.001) cancer. Cancer-specific survival was inferior for patients with breast (HR=1.29; p=0.03), colon (HR=1.75; p<0.001), and lung cancer (HR=1.17; p<0.001) who had pre-existing CLL after adjusting for age and sex. Conclusions: Several common cancers, including breast, colon, and lung, have inferior overall and cancer-specific survival when there is coexistent CLL. [Table: see text]

Download Full-text

Abstract P135: Varenicline and the Risk of Adverse Cardiovascular Events: A Population-Based Cohort Study

Circulation ◽

10.1161/circ.129.suppl_1.p135 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Kristian B Filion ◽

Sophie Dell'Aniello ◽

Maria Eberg ◽

Christel Renoux ◽

Stella S Daskalopoulou ◽

...

Keyword(s):

Smoking Cessation ◽

Cohort Study ◽

Cardiovascular Events ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards Model ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Increased Risk ◽

The Mean

Background: Clinical trial results suggest that varenicline is the most efficacious smoking cessation therapy. However, its cardiovascular safety is controversial, with recent meta-analyses providing conflicting results. Our objective was to compare the effect of varenicline to that of bupropion on the risk of cardiovascular events. Methods: We conducted a population-based cohort study of new users of varenicline or bupropion using data extracted from the UK’s Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics. Our primary endpoint was a composite of myocardial infarction, coronary revascularization, stroke, and all-cause mortality. An ‘as-treated’ analysis with a Cox proportional hazards model was used, with patients censored 7 days after the end of their last prescription or upon switching smoking cessation drugs. In secondary analyses, we compared varenicline and bupropion to nicotine replacement therapy (NRT) in pairwise comparisons. All analyses used high-dimensional propensity scores to adjust for potential confounding. Results: Our primary cohort included 90,522 varenicline users and 12,640 bupropion users. The mean age was 44 years, and 48% were men. The mean treatment duration was 45 days. A total of 128 events occurred among varenicline users, and 15 occurred among bupropion users. Although estimates suggest that varenicline may modestly increase the risk of cardiovascular events compared to bupropion, they were accompanied by wide 95% CIs (Table). Both varenicline and bupropion users had significantly lower risks of cardiovascular events than NRT users (Table). Conclusions: While we cannot exclude a modestly increased risk of cardiovascular events with varenicline relative to bupropion, such events remain rare, and both varenicline and bupropion are associated with a decreased risk of cardiovascular events compared with NRT. The long-term benefits obtained due to the increased smoking abstinence with varenicline likely outweigh any increased cardiovascular risk.

Download Full-text