Oral decitabine-cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study.

BACKGROUND: The DNA methyltransferase inhibitors azacitidine and decitabine for individuals with myelodysplastic syndromes or chronic myelomonocytic leukaemia are available in parenteral form. Oral therapy with similar exposure for these diseases would offer potential treatment benefits. We aimed to compare the safety and pharmacokinetics of oral decitabine plus the cytidine deaminase inhibitor cedazuridine versus intravenous decitabine. METHODS: We did a registrational, multicentre, open-label, crossover, phase 3 trial of individuals with myelodysplastic syndromes or chronic myelomonocytic leukaemia and individuals with acute myeloid leukaemia, enrolled as separate cohorts; results for only participants with myelodysplastic syndromes or chronic myelomonocytic leukaemia are reported here. In 37 academic and community-based clinics in Canada and the USA, we enrolled individuals aged 18 years or older who were candidates to receive intravenous decitabine, with Eastern Cooperative Oncology Group performance status 0 or 1 and a life expectancy of at least 3 months. Participants were randomly assigned (1:1) to receive 5 days of oral decitabine-cedazuridine (one tablet once daily containing 35 mg decitabine and 100 mg cedazuridine as a fixed-dose combination) or intravenous decitabine (20 mg/m2 per day by continuous 1-h intravenous infusion) in a 28-day treatment cycle, followed by 5 days of the other formulation in the next treatment cycle. Thereafter, all participants received oral decitabine-cedazuridine from the third cycle on until treatment discontinuation. The primary endpoint was total decitabine exposure over 5 days with oral decitabine-cedazuridine versus intravenous decitabine for cycles 1 and 2, measured as area under the curve in participants who received the full treatment dose in cycles 1 and 2 and had decitabine daily AUC0-24 for both oral decitabine-cedazuridine and intravenous decitabine (ie, paired cycles). On completion of the study, all patients were rolled over to a maintenance study. This study is registered with ClinicalTrials.gov, NCT03306264. FINDINGS: Between Feb 8, 2018, and June 7, 2021, 173 individuals were screened, 138 (80%) participants were randomly assigned to a treatment sequence, and 133 (96%) participants (87 [65%] men and 46 [35%] women; 121 [91%] White, four [3%] Black or African-American, three [2%] Asian, and five [4%] not reported) received treatment. Median follow-up was 966 days (IQR 917-1050). Primary endpoint of total exposure of oral decitabine-cedazuridine versus intravenous decitabine was 98·93% (90% CI 92·66-105·60), indicating equivalent pharmacokinetic exposure on the basis of area under the curve. The safety profiles of oral decitabine-cedazuridine and intravenous decitabine were similar. The most frequent adverse events of grade 3 or worse were thrombocytopenia (81 [61%] of 133 participants), neutropenia (76 [57%] participants), and anaemia (67 [50%] participants). The incidence of serious adverse events in cycles 1-2 was 31% (40 of 130 participants) with oral decitabine-cedazuridine and 18% (24 of 132 participants) with intravenous decitabine. There were five treatment-related deaths; two deemed related to oral therapy (sepsis and pneumonia) and three to intravenous treatment (septic shock [n=2] and pneumonia [n=1]). INTERPRETATION: Oral decitabine-cedazuridine was pharmacologically and pharmacodynamically equivalent to intravenous decitabine. The results support use of oral decitabine-cedazuridine as a safe and effective alternative to intravenous decitabine for treatment of individuals with myelodysplastic syndromes or chronic myelomonocytic leukaemia. FUNDING: Astex Pharmaceuticals.

Do Admitted COVID-19-Positive Patients on Anticoagulation Therapy Have a Reduced Hospital Stay and Disease Severity?

Background As of December 2021, the coronavirus disease 2019 (COVID-19) pandemic has resulted in the deaths of over 5 million people. It is known that infection with this virus causes a state of hypercoagulability. Because of this, there has been considerable debate on whether or not patients should be placed on anticoagulation prophylaxis/therapy. The goal of our project was to shed light on this topic by examining the effects of preexisting anticoagulation therapy in COVID-19 patients on disease severity (measured by blood clot readmissions, transfusion counts, and length of hospital stay). In this retrospective cohort study, we conducted an analysis based on data from 30,076 COVID-19-positive patients' electronic medical records. Materials and methods This is a retrospective cohort study. Patients included in this study were identified from the HCA Healthcare corporate database. Registry data was sourced from HCA East Florida hospitals. All patients included in this study were COVID-19 positive via polymerase chain reaction (PCR) or rapid antigen testing on admission and over age 18. A total of 30,076 patients were included in this study with hospital admission dates from March 1, 2020 to June 30, 2021. The analysis examined the relationship between age, sex, blood clot history, and most importantly current anticoagulation status on COVID-19 disease severity (through blood clot readmissions, length of stay, and transfusion count). Blood clot readmissions were analyzed with a logistic regression model while the length of hospital stay and transfusion count were analyzed with a linear regression model. Results Our analysis revealed that the odds of experiencing a blood clot readmission is 2.017 times more likely in patients already on anticoagulation therapy compared to those who were not (p = 0.0024). We also found that patients on anticoagulation therapy had a hospital stay of 6.90 days longer on average than patients not on anticoagulation therapy (p < 0.0001). Finally, patients on anticoagulation therapy had, on average, 0.20 more blood transfusions than patients not on anticoagulation therapy (p < 0.001).  Conclusion While these findings may be affected by the underlying conditions of those on preexisting anticoagulation therapy, they provide valuable insight into the debate on whether COVID-19-positive patients should be anticoagulated on admission to a hospital.

Hypercoagulopathy in Overweight and Obese COVID-19 Patients: a Single-Center Case Series.

A case series is presented of five overweight or obese patients with confirmed coronavirus disease 2019 (COVID-19) in South Miami, Florida, United States. A multitude of coagulation parameters was suggestive of a hypercoagulable state among the hospitalized COVID-19 patients. This article reports various manifestations of hypercoagulable states in overweight and obese patients, such as overt bleeding consistent with disseminated intravascular coagulation, venous thromboembolism, gastrointestinal bleeding as well as retroperitoneal hematoma. All of the required admission to the intensive care unit and subsequently patients died. The characteristics of COVID-19-associated coagulopathy are atypical and warrant a further understanding of the pathophysiology to improve clinical outcomes, specifically in overweight or obese patients.

High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections.

Severe COVID-19 disease is associated with an increase in pro-inflammatory markers, such as IL-1, IL-6, and tumor necrosis alpha, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells, which increase the susceptibility to bacterial and fungal infections. One such opportunistic fungal infection is mucormycosis. Initially, it was debated whether a person taking immunosuppressants, such as corticosteroids, and monoclonal antibodies will be at higher risk for COVID-19 or whether the immunosuppresive state would cause a more severe COVID-19 disease. However, immunosuppressants are currently continued unless the patients are at greater risk of severe COVID-19 infection or are on high-dose corticosteroids therapy. As understood so far, COVID-19 infection may induce significant and persistent lymphopenia, which in turn increases the risk of opportunistic infections. It is also noted that 85% of the COVID-19 patients' laboratory findings showed lymphopenia. This means that patients with severe COVID-19 have markedly lower absolute number of T lymphocytes, CD4+T and CD8+ T cells and, since the lymphocytes play a major role in maintaining the immune homeostasis, the patients with COVID-19 are highly susceptible to fungal co-infections. This report is intended to raise awareness of the importance of early detection and treatment of mucormycosis and other fungal diseases, such as candidiasis, SARS-CoV-2-associated pulmonary aspergillosis, pneumocystis pneumonia and cryptococcal disease, in COVID-19 patients, to reduce the risk of mortality.

Effect of cardiovascular drugs on cardiovascular events in 1599 patients followed in an academic outpatient cardiology practice.

This study investigated the effects of medical therapy on incidences of myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABG) in an academic outpatient cardiology practice. Chart reviews were performed in 1599 treated patients (1138 men and 461 women), mean age 72 years. Medications investigated included the use of statins, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and aspirin. The mean follow-up was 63 months during 1977-2009. Of 1599 patients, MI occurred in 100 patients (6%), PCI occurred in 296 patients (19%), and CABG occurred in 235 patients (15%). Stepwise logistic regression analysis showed that significant independent risk factors for MI were statins [odds ratio = 0.07; 95% confidence interval (CI), 0.05-0.11, P < 0.001], beta blockers (odds ratio = 0.15, 95% CI, 0.10-0.23, P < 0.001), ACE inhibitors (odds ratio = 0.27, 95% CI, 0.16-0.45, P < 0.001), ARBs (odds ratio = 0.09, 95% CI, 0.04-0.20, P < 0.001), and aspirin (odds ratio = 0.18, 95% CI, 0.12-0.29, P < 0.001). Significant independent risk factors for PCI were statins (odds ratio = 0.15, 95% CI, 0.11-0.20, P < 0.001), beta blockers (odds ratio = 0.26, 95% CI, 0.20-0.35, P < 0.001), ACE inhibitors (odds ratio = 0.25, 95% CI, 0.18-0.34, P < 0.001), and ARBs (odds ratio = 0.18, 95% CI, 0.11-0.28, P < 0.001). Significant independent risk factors for CABG were statins (odds ratio = 0.16, 95% CI, 0.12-0.22, P < 0.001), beta blockers (odds ratio = 0.43, 95% CI, 0.32-0.58, P < 0.001), ACE inhibitors (odds ratio = 0.38, 95% CI, 0.27-0.53, P < 0.001), ARBs (odds ratio = 0.19, 95% CI, 0.11-0.31, P < 0.001), and aspirin (odds ratio = 0.45, 95% CI, 0.33-0.61, P < 0.001).

Risk factor reduction in progression of angiographic coronary artery disease.

INTRODUCTION: To investigate differences between outpatients with progressive and nonprogressive coronary artery disease (CAD) measured by coronary angiography. MATERIAL AND METHODS: Chart reviews were performed in patients in an outpatient cardiology practice having ≥ 2 coronary angiographies ≥ 1 year apart. Progressive CAD was defined as 1) new non-obstructive or obstructive CAD in a previously disease-free vessel; or 2) new obstruction in a previously non-obstructive vessel. Coronary risk factors, comorbidities, cardiovascular events, medication use, serum low-density lipoprotein cholesterol (LDL-C), and blood pressure were used for analysis. RESULTS: The study included 183 patients, mean age 71 years. Mean follow-up duration was 11 years. Mean follow-up between coronary angiographies was 58 months. Of 183 patients, 108 (59%) had progressive CAD, and 75 (41%) had nonprogressive CAD. The use of statins, ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aspirin was not significantly different in patient with progressive CAD or nonprogressive CAD Mean arterial pressure was higher in patients with progressive CAD than in patients with nonprogressive CAD (97±13 mm Hg vs. 92±12 mm Hg) (p<0.05). Serum LDL-C was insignificantly higher in patients with progressive CAD (94±40 mg/dl) than in patients with nonprogressive CAD (81±34 mg/dl) (p=0.09). CONCLUSIONS: Our data suggest that in addition to using appropriate medical therapy, control of blood pressure and serum LDL-C level may reduce progression of CAD.

The impact of statin therapy on long-term cardiovascular outcomes in an outpatient cardiology practice.

INTRODUCTION: Statins reduce coronary events in patients with coronary artery disease. MATERIAL AND METHODS: Chart reviews were performed in 305 patients (217 men and 88 women, mean age 74 years) not treated with statins during the first year of being seen in an outpatient cardiology practice but subsequently treated with statins. Based on the starting date of statins use, the long-term outcomes of myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABGs) before and after statin use were compared. RESULTS: Mean follow-up was 65 months before statins use and 66 months after statins use. Myocardial infarction occurred in 31 of 305 patients (10%) before statins, and in 13 of 305 patients (4%) after statins (p < 0.01). Percutaneous coronary intervention had been performed in 66 of 305 patients (22%) before statins and was performed in 41 of 305 patients (13%) after statins (p < 0.01). Coronary artery bypass graft surgery had been performed in 56 of 305 patients (18%) before statins and in 20 of 305 patients (7%) after statins (p < 0.001). Stepwise logistic regression showed statins use was an independent risk factor for MI (odds ratio = 0.0207, 95% CI, 0.0082-0.0522, p < 0.0001), PCI (odds ratio = 0.0109, 95% CI, 0.0038-0.0315, p < 0.0001) and CABGs (odds ratio = 0.0177, 95% CI = 0.0072-0.0431, p < 0.0001) CONCLUSIONS: Statins use in an outpatient cardiology practice reduces the incidence of MI, PCI, and CABGs.

Reduction in atherosclerotic events: a retrospective study in an outpatient cardiology practice.

INTRODUCTION: Although atherosclerotic disease cannot be cured, risk of recurrent events can be reduced by application of evidence-based treatment protocols involving aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statin medications. We studied atherosclerotic event rates in a patient population treated before and after the development of aggressive risk factor reduction treatment protocols. MATERIAL AND METHODS: We performed a retrospective chart review of patients presenting for follow-up treatment of coronary artery disease in a community cardiology practice, comparing atherosclerotic event rates and medication usage in a 2-year treatment period prior to 2002 and a 2-year period in 2005-2008. Care was provided in both the early and later eras by 7 board-certified cardiologists in a suburban cardiology practice. Medication usage was compared in both treatment eras. The primary outcome was a composite event rate of myocardial infarction, cerebrovascular events, and coronary interventions. RESULTS: Three hundred and fifty-seven patients were studied, with a follow-up duration of 12.1 (±3.5) years. There were 132 composite events in 104 patients (29.1%) in the early era compared to 40 events in 33 patients (9.2%) in the later era (p < 0.0001). From the early to the later eras, there was an increase in use of ß-blockers (66% to 83%, p < 0.0001), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (34% to 80%, p < 0.0001), and statins (40% to 90%, p < 0.0001). CONCLUSIONS: Application of aggressive evidence-based medication protocols for treatment of atherosclerosis is associated with a significant decrease in atherosclerotic events or need for coronary intervention.

The impact of statin therapy on long-term cardiovascular outcomes in an outpatient cardiology practice.

BACKGROUND: Statins reduce coronary events in patients with coronary artery disease. MATERIAL/METHODS: Chart reviews were performed in 305 patients (217 men and 88 women, mean age 74 years) not treated with statins during the first year of being seen in an outpatient cardiology practice but subsequently treated with statins. Based on the starting date of statins use, the long-term outcomes of myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABGS) before and after statin use were compared. RESULTS: Mean follow-up was 65 months before statins use and 66 months after statins use. MI occurred in 31 of 305 patients (10%) before statins, and in 13 of 305 patients (4%) after statins (p < 0.01). PCI had been performed in 66 of 305 patients (22%) before statins and was performed in 41 of 305 patients (13%) after statins (p < 0.01). CABGS had been performed in 56 of 305 patients (18%) before statins and was performed in 20 of 305 patients (7%) after statins (p < 0.001). Stepwise logistic regression showed statins use was an independent risk factor for MI (odds ratio = 0.0207, 95% CI, 0.0082-0.0522, p < 0.0001), PCI (odds ratio = 0.0109, 95% CI, 0.0038-0.0315, p < 0.0001), and CABGS (odds ratio = 0.0177, 95% CI = 0.0072-0.0431, p<0.0001.) CONCLUSIONS: Statins use in an outpatient cardiology practice reduces the incidence of MI, PCI, and CABGS.

T cell lymphoma presenting as esophageal obstruction and bronchoesophageal fistula.

BACKGROUND: The mediastinum is an uncommon location for presentation of peripheral T cell lymphoma. Esophageal involvement by non-Hodgkin's lymphoma is extremely unusual. Although staging can be performed with routine imaging studies, surgical intervention is often required to ensure accurate histologic diagnosis of these lymphomas. Peripheral T cell lymphomas not otherwise specified are among the most aggressive non-Hodgkin lymphomas with often a poor response to conventional chemotherapy. CASE REPORT: We report a case of a 63 year-old-man with an aggressive mediastinal T cell lymphoma presenting as esophageal obstruction and bronchoesophageal fistula. The patient was treated with a cyclophosphamide, vincristine, and prednisone (COP) regimen. Repeat computer tomography scan of the chest after chemotherapy noted a significant decrease in the cavitary lesion in the right paraesophageal region and right mediastinum. Bronchoscopy revealed a large opening in the posterior wall of the bronchus intermedius leading into the esophagus. A fistulogram was done which clearly demonstrated a fistulous tract between the lower esophagus and the right intermediate bronchus secondary to perforation from the lymphoma. The patient eventually underwent cervical esophagostomy and jejunostomy tube placement to correct the brochoesophageal fistula. CONCLUSIONS: The mediastinum is an uncommon location for presentation of peripheral T cell lymphomas, and surgical intervention is often required to ensure accurate histological diagnosis of these lymphomas. In our patient, aggressive mediastinal T cell lymphoma presented as esophageal obstruction and bronchoesophageal fistula.

Patients with ischemic stroke have a higher prevalence of a planar QRS-T angle >90° than patients with transient ischemic attack.

BACKGROUND: The aim of the study was to investigate the prevalence of a planar QRS-T angle >90° in patients with ischemic stroke versus transient ischemic attack (TIA). MATERIAL/METHODS: In a prospective study of 279 consecutive patients who had ischemic stroke (197 patients) or TIA (82 patients), the planar QRS-T angle was measured from a 12-lead electrocardiogram taken at the time of the stroke or TIA. All QRS-T angle measurements were made by 3 authors who agreed on the measurements and who were blinded to the clinical findings. A QRS-T angle >90° was considered abnormal. RESULTS: The mean age was 66±6 years in patients with ischemic stroke versus 62±6 years in patients with TIA (p=0.04). The mean body mass index and the prevalence of gender, smoking, hypertension, diabetes mellitus, dyslipidemia, and coronary artery disease were not significantly different between patients with ischemic stroke versus TIA. A QRS-T angle >90° was present in 55 of 197 patients (28%) with ischemic stroke and in 10 of 82 patients (12%) with TIA (p=0.004). CONCLUSIONS: The prevalence of a planar QRS-T angle >90° was higher in patients with ischemic stroke than in patients with TIA (p=0.004).

A case of explosive progression of hepatocellular carcinoma in a patient with common variable immunodeficiency (CVID).

OBJECTIVE: While it is well known that patients with common variable immunodeficiency (CVID) are predisposed to various malignancies, primarily non-Hodgkin's lymphoma and gastric carcinomas, to our knowledge no cases of hepatocellular carcinoma have been reported in the absence of preexisting liver disease. METHOD AND RESULTS: We report a 50-year-old male patient with CVID with a B- and T-cell deficiency. The patient was on prophylactic intravenous gammaglobulin and had received several years earlier a course of rituximab for an autoimmune disorder. He had no history of hepatitis. The patient developed a rapidly progressing hepatocellular carcinoma within 3 to 4 weeks. CONCLUSIONS: Although patients with CVID are predisposed to malignancies such as lymphoma and adenocarcinoma of the stomach, rapidly progressive hepatocellular carcinoma in the absence of any preexisting liver disease has not been described.

Cardiovascular manifestations in patients with thrombotic thrombocytopenic purpura: a single-center experience.

BACKGROUND: Cardiovascular manifestation in patients with thrombotic thrombocytopenic purpura. HYPOTHESIS: The aim of this study was to investigate the incidence of acute myocardial infarction (AMI), arrhythmias, congestive heart failure, and mortality in patients hospitalized for thrombotic thrombocytopenic purpura (TTP). METHODS: Thirty-eight patients (27 women and 11 men), mean age 44 years, were hospitalized with the diagnosis of TTP confirmed by a hematologist. We investigated the incidence of AMI which developed during hospitalization for TTP. AMI was diagnosed by new electrocardiographic changes, increased serum cardiac troponin I levels, and clinical symptomatology. The patients with AMI were also monitored for development of arrhythmias during hospitalization. RESULTS: Of the 38 patients, 8 (21%) developed new Q-wave AMI. There was no significant difference in baseline characteristics between patients who developed AMI and those who did not develop AMI. Of the 8 patients with AMI, 2 (25%) developed atrial fibrillation, 1 (13%) developed atrial flutter, 1 (13%) developed supraventricular tachycardia, and 2 (25%) developed congestive heart failure. Death occurred in 3 of 8 patients (38%) with AMI and in 1 of 30 patients (3%) without AMI (P < 0.01). CONCLUSIONS: New Q-wave AMI developed in 21% of 38 patients hospitalized with TTP. Supraventricular tachyarrhythmias developed in 50% of 8 patients with TTP who developed AMI. Patients hospitalized for TTP should be monitored for adverse cardiac events due to the high incidence of new AMI, supraventricular tachyarrhythmias, and mortality.

Prevalence of transthoracic echocardiographic abnormalities in patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

INTRODUCTION: This study investigated the prevalence of transthoracic echocardiographic abnormalities in patients with ischemic stroke (IS), subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH) in sinus rhythm. MATERIAL AND METHODS: The patients included 120 with IS, 30 with SAH, and 41 with ICH. All diagnoses were confirmed by magnetic resonance imaging or brain computed tomography. Two-dimensional echocardiograms were taken at the time stroke was diagnosed. All echocardiograms were interpreted by an experienced echocardiographer. RESULTS: Of 120 IS patients, 1 (1%) had a left ventricular (LV) thrombus, 1 (1%) had mitral valve vegetations, 30 (25%) had LV hypertrophy, 26 (22%) had abnormal LV ejection fraction, 4 (3%) had mitral valve prolapse, 33 (28%) had mitral annular calcium (MAC), 40 (33%) had aortic valve calcium (AVC), 3 (3%) had a bioprosthetic aortic valve, 10 (8%) had aortic stenosis (AS), 6 (5%) had atrial septal aneurysm, 2 (2%) had patent foramen ovale, and 40 (33%) had no abnormalities. Of 30 SAH patients, 5 (17%) had LV hypertrophy, 1 (3%) had abnormal LV ejection fraction, 1 (3%) had AS, 4 (13%) had MAC, 5 (17%) had AVC, and 20 (67%) had no abnormalities. Of 41 ICH patients, 9 (22%) had LVH, 1 (2%) had abnormal LV ejection fraction, 1 (3%) had AS, 6 (15%) had MAC, 8 (20%) had AVC, and 22 (54%) had no abnormalities. CONCLUSIONS: Transthoracic echocardiographic abnormalities are more prevalent in patients with IS than in patients with SAH or ICH.

Incidence of appropriate cardioverter-defibrillator shocks and mortality in patients with implantable cardioverter-defibrillators with ischemic cardiomyopathy versus nonischemic cardiomyopathy at 33-month follow-up.

INTRODUCTION: The aim of the study was to investigate at long-term follow-up the incidence of appropriate implantable cardioverter-defibrillator (ICD) shocks and of all-cause mortality in patients with ICDs with ischemic cardiomyopathy versus nonischemic cardiomyopathy. MATERIAL AND METHODS: ICDs were implanted in 485 patients with ischemic cardiomyopathy and in 299 patients with nonischemic cardiomyopathy, all of whom had coronary angiography. Baseline characteristics were not significantly different between the 2 groups. Follow-up was 965 days in patients with ischemic cardiomyopathy versus 1039 days in patients with nonischemic cardiomyopathy (p not significant). The ICDs were interrogated every 3 months to see if shocks occurred. RESULTS: Appropriate ICD shocks occurred in 179 of 485 patients (37%) with ischemic cardiomyopathy and in 93 of 299 patients (31%) with nonischemic cardiomyopathy (p not significant). All-cause mortality occurred in 162 of 485 patients (33%) with ischemic cardiomyopathy and in 70 of 299 patients (23%) with nonischemic cardiomyopathy (p = 0.002). CONCLUSIONS: The incidence of appropriate ICD shocks was not significantly different at 33-month follow-up in patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy. However, patients with ischemic cardiomyopathy had a significantly higher incidence of all-cause mortality than patients with nonischemic cardiomyopathy (p = 0.002).

Incidence of appropriate cardioverter-defibrillator shocks and mortality in patients with heart failure treated with combined cardiac resynchronization plus implantable cardioverter-defibrillator therapy versus implantable cardioverter-defibrillator therapy.

Of 529 patients with heart failure and a mean left ventricular ejection fraction of 29%, 209 (40%) were treated with cardiac resynchronization therapy (CRT) plus an implantable cardioverter-defibrillator (ICD) and 320 (60%) with an ICD. Mean follow-up was 34 months for both groups. Stepwise logistic regression analysis showed that significant independent variables for appropriate ICD shocks were statins (risk ratio = 0.35, P < .0001), smoking (risk ratio = 2.52, P < .0001), and digoxin (risk ratio = 1.92, P = .0001). Significant independent variables for time to deaths were use of CRT (risk ratio = 0.32, P = .0006), statins (risk ratio = 0.18, P < .0001), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (risk ratio = 0.10, P < .0001), hypertension (risk ratio = 24.15, P < .0001), diabetes (risk ratio = 2.54, P = .0005), and age (risk ratio = 1.06, P < .0001). In conclusion, statins reduced and smoking and digoxin increased appropriate ICD shocks. Use of CRT, statins, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers reduced mortality and hypertension, diabetes, and older age increased mortality.

Incidence of perioperative myocardial infarction and of 2-year mortality in 577 elderly patients undergoing noncardiac vascular surgery treated with and without statins.

Of 577 patients, mean age 74 years, undergoing noncardiac vascular surgery, 300 (52%) had carotid endarterectomy, 179 (31%) had lower extremity revascularization, and 98 (17%) had abdominal aortic aneurysm repair. Of the 577 patients, 302 (52%) were treated with statins. Perioperative myocardial infarction (MI) occurred in 18 of 302 patients (6%) treated with statins and in 38 of 275 patients (14%) not treated with statins (p=0.001). Two-year mortality occurred in 18 of 302 patients (6%) treated with statins and in 43 of 275 patients (16%) not treated with statins (p=0.0002). Perioperative MI or mortality occurred in 34 of 302 patients (11%) treated with statins and in 74 of 275 patients (27%) not treated with statins (p<0.0001). Stepwise Cox regression analysis showed that significant independent prognostic factors for perioperative MI or death were use of statins (risk ratio=RR=0.43, p<0.0001), use of beta blockers (RR=0.55, p=0.002), carotid endarterectomy (RR=0.60, p=0.009), and diabetes (RR=1.5, p=0.045). In conclusion, patients undergoing noncardiac vascular surgery treated with statins had a 57% less chance of having perioperative MI or death at 2-year follow-up after controlling for other variables.

Statins reduce appropriate cardioverter-defibrillator shocks and mortality in patients with heart failure and combined cardiac resynchronization and implantable cardioverter-defibrillator therapy.

Of 209 patients with heart failure treated with combined cardiac resynchronization therapy and implantable cardioverter-defibrillator therapy, appropriate cardioverter-defibrillator shocks occurred at 34-month follow-up in 22 of 121 patients (18%) on statins and in 30 of 88 patients (34%) not on statins (P = .009). Deaths occurred in 3 of 121 patients (2%) on statins and in 9 of 88 patients (10%) not on statins (P = .017). Stepwise Cox regression analysis showed that significant independent prognostic factors for appropriate shocks were use of statins (risk ratio = 0.46), smoking (risk ratio = 3.5), and diabetes (risk ratio = 0.34). Significant independent prognostic factors for the time to mortality were use of statins (risk ratio = 0.05), use of digoxin (risk ratio = 4.2), systemic hypertension (risk ratio = 14.2), diabetes (risk ratio = 4.3), and left ventricular ejection fraction (risk ratio = 1.1).

Relation of cardiac troponin I levels with in-hospital mortality in patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

Troponin I levels were drawn within 24 hours of stroke in 161 of 175 patients (92%) with ischemic stroke, 94 of 107 patients (88%) with intracerebral hemorrhage, and 96 of 96 patients (100%) with subarachnoid hemorrhage. A troponin level >0.4 ng/ml was considered increased. In patients with ischemic stroke, in-hospital mortality occurred in 15 of 23 patients (65%) with increased troponin I compared with 6 of 138 patients (4%) with normal troponin I (p <0.001). In patients with intracerebral hemorrhage, in-hospital mortality occurred in 9 of 14 patients (64%) with increased troponin I compared with 22 of 80 patients (28%) with normal troponin I (p <0.005). In patients with subarachnoid hemorrhage, in-hospital mortality occurred in 8 of 20 patients (40%) with increased troponin I compared with 8 of 76 patients (11%) with normal troponin I (p <0.005). In conclusion, patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage with elevated troponin I levels have increased in-hospital mortality.

Effect of beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins on mortality in patients with implantable cardioverter-defibrillators.

Nine hundred sixty-five patients (mean age 70 years) with implantable cardioverter-defibrillator were followed for 32 +/- 33 months for all-cause mortality. Death occurred in 73 of 515 patients (13%) treated with beta blockers (group 1), in 84 of 494 patients (17%) treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (group 2), in 56 of 402 patients (14%) treated with statins (group 3), in 40 of 227 patients (18%) treated with amiodarone (group 4), in 5 of 26 patients (19%) treated with sotalol (group 5), and in 64 of 265 patients (24%) treated with no beta blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, statin, amiodarone, or sotalol (group 6) (p <0.001 for group 1 vs group 6 and group 3 vs group 6, p <0.02 for group 2 vs group 6). In conclusion, patients with implantable cardioverter-defibrillators should be treated with beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins to reduce mortality.