Baseline Statin Research Articles

Time-dependent prognostic effect of high sensitivity C-reactive protein with statin therapy in acute myocardial infarction

BackgroundElevated high sensitivity C-reactive protein (hs-CRP) in acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI) has prognostic value for future cardiovascular events. This study aimed to ascertain a valid prognostic time-period for predicting cardiovascular outcome based on baseline hs-CRP in AMI patients undergoing successful PCI on statin therapy. MethodsOverall, 4410 AMI patients were enrolled from the Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) registry. Participants were divided into groups according to cut-off values of baseline hs-CRP (1.0, 3.0, and 10.0mg/L) and statin therapy intensity. The primary outcome was 36-month major adverse cardiovascular events (MACE), a composite of all-cause mortality, any myocardial infarction, and repeat revascularization. The secondary outcome was MACE developed 0–6, 6–12, and 12–36 months after AMI. ResultsThe overall incidence of 36-month MACE was significantly higher as baseline hs-CRP increased (by groups: 8.8% vs. 8.6% vs. 10.7% vs. 15.4%, log-rank p<0.001). The prognostic effect of baseline hs-CRP was mostly confined to the first 6 months after AMI (0–6 months MACE by groups: 1.6% vs. 2.3% vs. 4.3% vs. 6.1%, log-rank p<0.001) and attenuated in high-intensity statin users. Six months after AMI, this prognostic effect of baseline hs-CRP was remarkably reduced (6–12 month MACE by groups: 2.4% vs. 2.1% vs. 2.8% vs. 4.0%, log-rank p=0.111, 12–36 month MACE by groups: 4.7% vs. 4.1% vs. 4.0% vs. 6.2%, log-rank p=0.218); however, high-intensity statin treatment showed a consistent improvement in outcome. The observed time-dependent prognostic effects remained consistent following multivariate analysis. ConclusionsThe prognostic impact of elevated hs-CRP at baseline was most evident during the first 6 months after AMI; however, the use of high-intensity statin persistently improved the clinical outcome even after the resolution of inflammatory reactions.

Patients Prescribed Anakinra for Acute Gout Have Baseline Increased Burden of Hyperuricemia, Tophi, and Comorbidities, and Ultimate All-Cause Mortality.

Objective:The interleukin-1 (IL-1) receptor antagonist anakinra is an effective, off-label option in acute gout flares, when conventional therapy options are narrowed. We performed a retrospective, randomized, case-controlled study to gain clinical insight on baseline factors for gout patients most likely to receive anakinra, and ultimate mortality of those who received anakinra.Methods:Of 1451 gout patients seen between January 2003 and January 2015 in a Veterans Affairs (VA) rheumatology group practice, under stringent managed care principles, 13 (100% male), who received anakinra at least once for flares, were compared with 1:4 age- and sex-matched gout controls. Each patient’s first rheumatology encounter was studied by factor analysis for variables associated with later anakinra.Results:At baseline, patients that received anakinra had higher urate burden (palpable tophi [10/13] vs controls [16/52], P = .003), serum urate ([10.6 mg/dL] vs controls [7.6 mg/dL], P < .0001), and East Asian descent ([7/13] vs [16/52], P = .041). The anakinra group had higher ultimate all-cause mortality ([6/13] vs controls [7/52], relative risk [RR] = 3.43, 95% confidence interval [CI] = 1.39-8.48, P = .0076). Factor analysis showed baseline visit palpable tophus and statin use to be most strongly associated with later anakinra use. Increased mortality of anakinra users, as per a factorial analysis, was linked more strongly to comorbidities than to anakinra.Conclusions:At baseline rheumatology gout encounter, higher urate, palpable tophi, statin prescription, and East Asian descent were associated with later anakinra use for flares. Mortality was more closely associated to the presence of comorbidities at baseline rheumatology visit than to anakinra prescription.

Usefulness of baseline statin therapy in non-obstructive coronary artery disease by coronary computed tomographic angiography: From the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) study.

BackgroundThe extent to which the presence and extent of subclinical atherosclerosis by coronary computed tomography angiography influences a potential mortality benefit of statin is unknown. We evaluated the relationship between statin therapy, mortality, and subclinical atherosclerosis.MethodsIn the CONFIRM study, patients with normal or non-obstructive plaque (<50% diameter stenosis) for whom data on baseline statin use was available were included. Coronary artery calcium (CAC) was quantified using the Agatston score. The extent of non-obstructive coronary atherosclerosis was quantified using the segment involvement score (SIS). 8,016 patients were followed for a median of 2.5 years with analysis of all-cause mortality and major adverse cardiac events (MACE) including all-cause mortality, myocardial infarction, unstable angina, target vessel revascularization, and coronary artery disease-related hospitalization.Results1.2% of patients experienced all-cause mortality. Patients not on baseline statin therapy had a stepwise increased risk of all-cause mortality by CAC (relative to CAC = 0; CAC 1–99: hazard ratio [HR] 1.65, CAC 100–299: HR 2.19, and CAC≥300: HR 2.98) or SIS (relative to SIS = 0; SIS 1: HR 1.62, SIS 2–3: 2.48 and SIS≥4: 2.95). Conversely, in patients on baseline statin therapy, there was no significant increase in mortality risk with increasing CAC (p value for interaction = 0.049) or SIS (p value for interaction = 0.007). The incidence of MACE was 2.1%. Similar to the all-cause mortality, the risk of MACE was increased with CAC or SIS strata in patient not on baseline statin therapy. However, this relation was not observed in patient on baseline statin therapy.ConclusionIn individuals with non-obstructive coronary artery disease, increased risk of adverse events occurs with increasing CAC or SIS who are not on baseline statin therapy. Statin therapy is associated with a mitigation of risk of cardiac events in the presence of increasing atherosclerosis, with no particular threshold of disease burden.

Targeting Tumor Metabolism With Statins During Treatment for Advanced-stage Pancreatic Cancer.

A growing body of preclinical data suggests that statins may exert potent antitumor effects, yet the interactions of these medications with standard therapies and clinical outcomes in this population is less clear. We assessed the impact of statin use on outcomes in patients with advanced-stage pancreatic adenocarcinoma undergoing various treatments. After institutional review board approval, we conducted a retrospective-cohort study consisting of 303 newly diagnosed advanced-stage pancreatic adenocarcinoma patients to determine the impact of statin use on outcomes. Univariate and multivariable Cox proportional hazard regression models were utilized to estimate hazard ratios (HRs). Time-to-event was estimated using Kaplan-Meier survival analysis for overall survival, distant metastasis, and locoregional failure. Baseline and active statin usage were assessed and to mitigate risk of immortal time bias, subanalysis excluding patients with under 6 months of follow-up was conducted. Both prior (P=0.021) and active (P=0.030) statin usage correlated with improved survival in this cohort. Surgery, chemoradiation, and statin use improved 2-year survival rates (84.1% vs. 55.0%; P<0.001). On multivariable analysis, statin exposure was associated with overall survival (HR, 0.662; P=0.027) and trended to significance for freedom from distant metastasis (HR, 0.577; P=0.060). Comorbid conditions were not significantly associated with outcomes. Statin use was associated with improved overall survival in advanced-stage pancreatic adenocarcinoma patients. This data supports previous findings in early-stage pancreatic adenocarcinoma and other cancer sites. To our knowledge this is the first report to examine the efficacy of statin use as a supplementary treatment option in advanced-stage pancreatic adenocarcinoma patients.

Statins associate with improved mortality among patients with certain histological subtypes of lung cancer

ObjectivesTo measure the association between statin exposure and mortality in lung cancer patients belonging to different categories of histological subtype. Materials and methodsA cohort of 19,974 individuals with incident lung cancer between 2007 and 2011 was identified using the SEER-Medicare linked database. Statin exposure both pre- and post-diagnosis was analyzed to identify a possible association with cancer-specific mortality in patients stratified by histological subtype. Intention-to-treat analyses and time-dependent Cox regression models were used to calculate hazard ratios and 95% confidence intervals (95% CIs) corresponding to statin exposure both pre- and post-diagnosis, respectively. ResultsOverall baseline statin exposure was associated with a decrease in mortality risk for squamous-cell carcinoma patients (HR = 0.89, 95% CI = 0.82–0.96) and adenocarcinoma patients (HR = 0.87, 95% CI = 0.82–0.94), but not among those with small-cell lung cancer. Post-diagnostic statin exposure was associated with prolonged survival in squamous-cell carcinoma patients (HR = 0.68, 95% CI = 0.59–0.79) and adenocarcinoma patients (HR = 0.78, 95% CI = 0.68–0.89) in a dose-dependent manner. ConclusionThere is consistent evidence indicating that baseline or post-diagnostic exposure to simvastatin and atorvastatin is associated with extended survival in non-small-cell lung cancer subtypes. These results warrant further randomized clinical trials to evaluate subtype-specific effects of certain statins in patient cohorts with characteristics similar to those examined in this study.

Use of the CANHEART ‘big data’ registry to conduct a large randomized registry clinical trial to improve lipid management in Ontario, Canada

IntroductionCreation of registries using linked population-based databases could potentially be used to conduct large registry-based clinical trials. As part of the CANHEART-Strategy for Patient-Oriented Research (SPOR) innovative clinical trials initiative, we explored the practicality of using the linked CANHEART registry to conduct a cluster-randomized trial aimed at improving lipid management.&#x0D; Objectives and ApproachThe CANHEART registry (www.canheart.ca) was created through the linkage of 19 population-based health databases in Ontario, Canada, providing individual-level socio-demographic, geographic, hospitalization, disease testing/screening, mortality, prescription medication, and behavior/lifestyle information. Using CANHEART defined eligibility criterion, small and medium-sized, high cardiovascular-risk health regions (defined as having acute myocardial infarction, stroke or cardiovascular death rates greater than the Ontario average) are being randomly allocated to receive either the intervention (availability of a lipid management ‘toolbox’) or standard care. Cohort linkages to additional years of data will occur regularly over the 3-year trial to ascertain the primary outcome of appropriate statin prescribing rates.&#x0D; &#x0D; \section*{Results}&#x0D; Record linkage enabled us to determine baseline characteristics of 835,345 patients aged 40-75 as of January 2016, being treated in the 28 study-eligible regions by 2,012 family physicians. Preceding the study, the baseline statin use rate was 35.7\% (in 66-75 year olds) across these regions and the cardiovascular event rate ranged from 3.78-5.64 events/1000 person-years. A randomization procedure yielded 14 regions in both the intervention and control arms which did not differ significantly in socio-demographic characteristics, traditional cardiovascular risk factors, disease history, prevalence of statin use, or access to healthcare indicators. Working groups have been established to operationalize the lipid management tools that will be made available in the intervention regions. Analysis of newly linked participant data will permit outcome ascertainment at trial completion.&#x0D; &#x0D; \section*{Conclusion/Implications}&#x0D; Our work demonstrates the feasibility of using the CANHEART ‘big data’ registry to conduct a large, cluster-randomized clinical trial aimed at improving lipid management, without requiring any primary data collection. Broader use of this methodology has the potential to change the existing paradigm for conducting pragmatic clinical trial research.

Optimal duration for continuation of statin therapy in bacteremic patients.

Evidence suggests statins may improve survival in patients with bloodstream infections. However, there is no consensus on optimal timing and duration of exposure. To quantify statin therapy duration associated with decreased mortality in bacteremic statin users. We conducted a case-control study using OptumClinformatics™ with matched Premier hospital data (1 October 2009-31 March 2013). Cases who died during the hospitalization were matched 1:1 to survivors on disease risk scores (DRSs). Post-admission statin therapy duration was evaluated in patients with at least 90 days of pre-admission continuous statin use. Classification and regression tree (CART) analysis was conducted to identify the optimal duration of statin continuation which provided the lowest inpatient mortality. Logistic regression was used to calculate the odds of mortality. We included 58 DRS matched pairs of cases and controls: 47 patients (41%) continued statin therapy during the hospital admission, 15 (32%) cases and 32 (68%) controls. The CART analysis partitioned the continuation of statin therapy at ⩾2 days, representing lower mortality for patients who continued statins for 2 days or more and higher mortality for patients who did not continue or remained on statins for only 1 day. Inpatient mortality was 76% lower among those with at least 2 days of continued statin use (odds ratio 0.24, 95% confidence interval 0.11-0.55). Among matched cases and controls with at least 90 days of baseline statin use prior to the admission, the continuation of statins for at least 2 days after admission demonstrated a survival benefit among bacteremic patients.

Serum PCSK9 levels predict the occurrence of acute coronary syndromes in patients with severe carotid artery stenosis

BackgroundThe pharmacological inhibition of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has shown to dramatically impact on low-density lipoprotein-cholesterol (LDL-C) levels and associated cardiovascular (CV) diseases. However, the potential use of PCSK9 serum levels as a CV risk biomarker remains to be clarified. Methods189 patients with severe carotid artery atherosclerosis undergoing carotid endarterectomy (CEA) and whose clinical records and serum sample aliquots for PCSK9 level measurement were available both directly before CEA and at 24-month follow-up were included in the present pilot study. The study endpoint was to determine whether PCSK9 serum levels prior to CEA would predict the occurrence of acute coronary syndromes (ACS) at 24-month follow-up. ResultsPCSK9 serum levels were significantly accurate in predicting ACS at 24-month follow-up, as assessed by ROC curve analysis (AUC: 0.719 [95% CI 0.649–0.781]). According to the cut-off point indicated by Youden's index, PCSK9 values >431.3 ng/mL were correlated with a higher risk of ACS occurrence (Log Rank test, p = 0.0003). At Cox regression analysis, the predictive ability of high serum PCSK9 was confirmed also after adjustment for age, gender, baseline statin treatment and active smoking, dyslipidemia, and chronic coronary artery disease (HR 17.04 [95% CI 3.34–86.81]; p = 0.001). ConclusionsHigh serum PCSK9 levels predict ACS occurrence at 24-month follow-up after CEA in patients with severe carotid artery stenosis. Larger clinical studies are needed to evaluate whether PCSK9 serum levels could be used towards predicting the risk of ACS in patients with advanced carotid atherosclerosis.

Desirable Low-Density Lipoprotein Cholesterol Levels for Preventing Stroke Recurrence: A Post Hoc Analysis of the J-STARS Study (Japan Statin Treatment Against Recurrent Stroke).

To define desirable target low-density lipoprotein (LDL) cholesterol levels for the prevention of stroke recurrence, a post hoc analysis was performed in the J-STARS study (Japan Statin Treatment Against Recurrent Stroke). Subjects (n=1578) were divided into groups based on mean value of postrandomized LDL cholesterol levels until the last observation in 20 mg/dL increments. Adjusted hazard ratios (HRs) and 95% confidence intervals were analyzed for each group, with adjustments for baseline LDL cholesterol, baseline body mass index, hypertension, diabetes mellitus, and statin usage. The postrandomized LDL cholesterol level until the last observation were 104.1±19.3 mg/dL in the pravastatin group and 126.1±20.6 mg/dL in the control group. The adjusted HRs for stroke and transient ischemic attack and all vascular events decreased in the postrandomized LDL cholesterol level of 80 to 100 mg/dL (P=0.23 and 0.25 for the trend, respectively). The adjusted HR for atherothrombotic infarction significantly reduced with the usage of statin after adjusting baseline LDL cholesterol levels (HR, 0.39; 95% confidence intervals, 0.19-0.83). The adjusted HR for atherothrombotic infarction and intracranial hemorrhage were similar among the postrandomized LDL-cholesterol-level subgroups (P=0.50 and 0.37 for the trend, respectively). The adjusted HR for lacunar infarction decreased in the postrandomized LDL cholesterol level of 100 to 120 mg/dL (HR, 0.45; 95% confidence intervals, 0.20-0.99; P=0.41 for the trend). The composite risk of stroke and transient ischemic attack reduced in the postrandomized LDL cholesterol level of 80 to 100 mg/dL after adjusting for statin usage. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00221104.

RELATIONSHIP BETWEEN STATIN USE AND TRIMETHYLAMINE N-OXIDE IN CARDIOVASCULAR RISK ASSESSMENT

Trimethylamine N-Oxide (TMAO) is a gut microbiota generated metabolite implicated in the development of cardiovascular disease. However, it is unknown how this metabolite responds to statin, a common medication utilized in this patient population. Plasma TMAO and baseline statin use data was

Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies.

ObjectivesLipid profiles are altered by active disease in patients with rheumatoid arthritis (RA) and may be further modified by treatment with Janus kinase inhibitors and other disease-modifying antirheumatic drugs.MethodsLipid data were analysed from phase II and III studies of 4 mg (n=997) and 2 mg (n=479) oral baricitinib administered once daily in patients with moderate-to-severe active RA. Lipoprotein particle size and number and GlycA were evaluated with nuclear magnetic resonance in one phase III study. The effect of statin therapy on lipid levels was evaluated in patients on statins at baseline and in patients who initiated statins during the study.ResultsTreatment with baricitinib was associated with increased levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides, but no significant change in LDL-C:HDL-C ratio. Lipid levels plateaued after 12 weeks of treatment. Baricitinib treatment increased large LDL and decreased small, dense LDL particle numbers and GlycA. Lipid changes from baseline were not significantly different between baseline statin users and non-users. In patients who initiated statin therapy during the study, LDL-C, triglycerides (baricitinib 4 mg only) and apolipoprotein B decreased to pre-baricitinib levels; HDL-C and apolipoprotein A-I levels remained elevated.ConclusionsBaricitinib was associated with increased LDL-C, HDL-C and triglyceride levels, but did not alter the LDL-C:HDL-C ratio. Evaluation of cardiovascular event rates during long-term treatment is warranted to further characterise these findings and their possible clinical implications.Trial registration numberNCT00902486, NCT01469013, NCT01185353, NCT01721044, NCT01721057, NCT01711359, NCT01710358, NCT01885078.

An analysis of the association between statin use and risk of endometrial and ovarian cancers in the Women's Health Initiative

BackgroundStatins have anti proliferative activity in vitro against endometrial and ovarian cancer and can affect levels of reproductive hormones. We analyzed data from the Women's Health Initiative (WHI) to assess whether statins are associated with risk of endometrial and ovarian cancer. MethodsThe WHI study included 161,808 postmenopausal women in which incident cases of endometrial (n = 1377) and ovarian cancer (n = 763) were identified over an average of 10.8 (SD + 3.3) years. Information on statin use and risk factors was collected at baseline and follow-up. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of statin use and risk of endometrial and ovarian cancer. All statistical tests were two-sided. ResultsStatins were used at baseline by 7.5% women and by up to 25% at year nine. The multivariable adjusted HR for risk of endometrial cancer for baseline statin use was 0.74, 95% C.I. 0.59–0.94 and for ovarian cancer was 1.15, 95% C.I. 0.89–1.50. In time-dependent models, statins were not associated with endometrial cancer (HR 0.91, 95% C.I. 0.76–1.08) however there was an increased risk of ovarian cancer (HR 1.30, 95% CI 1.04–1.62), largely attributed to the effect of the hydrophilic statin, pravastatin (1.89, 95% CI 1.24–2.88). ConclusionsThere was a reduction in risk of endometrial cancer among statin users at baseline but not in time-dependent models. Pravastatin use was associated with an increased risk of ovarian cancer. Analyses of larger numbers of cases are needed to evaluate these findings.

Liraglutide reduces cardiovascular events and mortality in type 2 diabetes mellitus independently of baseline low-density lipoprotein cholesterol levels and statin use results from the LEADER trial

Liraglutide reduces cardiovascular events and mortality in type 2 diabetes mellitus independently of baseline low-density lipoprotein cholesterol levels and statin use results from the LEADER trial

Implications of New Cholesterol Treatment Guidelines on Statin Utilization, Intensity, and Costs in Active Duty Service Members.

The recommendations in the 2013 American College of Cardiology/American Heart Association (ACC/AHA) blood cholesterol guidelines expanded the indications and level of intensity of statin therapy for the primary prevention of cardiovascular disease. We assessed the treatment and cost implications of theseguidelines within a cohort of active duty service members. Using the military electronic medical record system, the Armed Forces Health Longitudinal Technology Application, we randomly selected 1,000 active duty persons aged 40 yr or older and reviewed their lipid profiles and medical records to identify risk factors for atherosclerotic cardiovascular disease. We compared the recommended cholesterol treatment under the new ACC/AHA guidelines versus the Third Adult Treatment Panel of the National Cholesterol Education Program. The mean age was 49 ± 7 yr, 36% were female, 22% were on baseline statin therapy (4% high intensity), and 13% were not at Third Adult Treatment Panel cholesterol goal. There was no difference in the proportion eligible for statin therapy between ACC/AHA and Third Adult Treatment Panel guidelines. Statin treatment under the ACC/AHA guideline resulted in a mean statin dose increase from 25 ± 20 mg to 36 ± 25 mg (p < 0.001) with an increase in those eligible for high-intensity statin therapy, 6% to 11% (p < 0.001). These changes translated to higher estimated yearly statin acquisition costs, $40,197 versus $52,527 per 1,000 patient-years of treatment (p < 0.001). Within a low-risk active duty population over 40 yr, application of the 2013 ACC/AHA cholesterol treatment guidelines may not significantly increase those eligible for statins, but may increase statin treatment intensity and costs.

Effect of statin on arginine metabolites in treated HIV-infection

Background and aimsAsymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide and an independent risk factor for cardiovascular disease. We examined the effect of statin on ADMA in HIV + patients on stable ART, and whether such an effect contributes to the favorable changes on carotid intima media thickness. MethodsThis is a secondary analysis of SATURN-HIV, in which HIV + adults on stable ART with HIV-1 RNA< 1000 copies/mL and LDL-cholesterol <130 mg/dL were randomized to 10 mg daily rosuvastatin or placebo. Arginine metabolites, ADMA, and markers of inflammation were assessed at baseline and 48 weeks. Carotid intima media thickness (c-IMT) was measured at baseline, 48 and 96 weeks. Spearman correlations, and linear mixed-effect models were used to study relationships among variables. ResultsOverall, 79% were male, 68% African Americans, with a median age of 46 years. In the statin arm, no change in ADMA levels was observed at 48 weeks (0.70%), whereas a trend towards an increase in ADMA levels (23.78%) was observed in the placebo group (p = 0.06). Elevated baseline ADMA (highest tertile) was associated with a 0.04 mm increase in c-IMT (p = 0.03) after adjusting for statin and study duration. No interaction was seen between baseline ADMA and statin randomization on change in c-IMT (p = 0.21). ConclusionsIn HIV + subjects on ART, rosuvastatin suppressed the increase over time in ADMA levels. Elevated baseline levels of ADMA were associated with increases in c-IMT, regardless of statin assignment. The favorable effect of rosuvastatin on c-IMT appears to be independent of the arginine pathway.

Predictors and Outcomes of Postcontrast Acute Kidney Injury after Endovascular Renal Artery Intervention

PurposeTo determine incidence, predictors, and clinical outcomes of postcontrast acute kidney injury (PC-AKI) following renal artery stent placement for atherosclerotic renal artery stenosis. Materials and MethodsThis retrospective study reviewed 1,052 patients who underwent renal artery stent placement for atherosclerotic renal artery stenosis; 437 patients with follow-up data were included. Mean age was 73.6 years ± 8.3. PC-AKI was defined as absolute serum creatinine increase ≥ 0.3 mg/dL or percentage increase in serum creatinine ≥ 50% within 48 hours of intervention. Logistic regression analysis was performed to identify risk factors for PC-AKI. The cumulative proportion of patients who died or went on to hemodialysis was determined using Kaplan-Meier survival analysis. ResultsMean follow-up was 71.1 months ± 68.4. PC-AKI developed in 26 patients (5.9%). Patients with PC-AKI had significantly higher levels of baseline proteinuria compared with patients without PC-AKI (odds ratio = 1.38; 95% confidence interval, 1.11–1.72; P = .004). Hydration before intervention, chronic kidney disease stage, baseline glomerular filtration rate, statin medications, contrast volume, and iodine load were not associated with higher rates of PC-AKI. Dialysis-free survival and mortality rates were not significantly different between patients with and without PC-AKI (P = .50 and P = .17, respectively). ConclusionsElevated baseline proteinuria was the only predictor for PC-AKI in patients undergoing renal artery stent placement. Patients who developed PC-AKI were not at greater risk for hemodialysis or death.

Risk of Cause-Specific Death in Individuals with Cancer-Modifying Role Diabetes, Statins and Metformin.

Both diabetes mellitus (DM) and cancer are common diseases and they frequently occur in the same patients. We investigated the all-cause and cause-specific mortality dynamics in relation to baseline DM, statin use and metformin use. The study population consisted of 39,900 incident cancer cases from Finland, 19,822 patients were free of DM at the start of follow-up and 20,078 had DM. Mortality from all causes, and cancer, cardiovascular (CVD) and other causes was analysed using Poisson regression model with the following variables: sex, age, DM, statin and metformin usage in baseline, cancer type and stage and calendar period. Statin usage was associated with a reduced cancer-specific mortality with incidence rate ratio (IRR) 0.72 (95% confidence interval 0.69-0.74), IRR for CVD mortality was 0.95 (0.88-1.02) and for other causes 0.64 (0.56-0.74). In a sub-population of DM patients, IRR for metformin in all-cause mortality was 0.74 (0.71-0.78), in cancer mortality 0.75 (0.72-0.79), in CVD mortality 0.75 (0.68-0.83) and other causes 0.68 (0.60-0.78). In conclusion, our register-based study of survival after cancer diagnosis showed that patients with diabetes had substantially poorer outcome in all measures. An association between baseline statin usage and lower all-cause, cancer and cardiovascular mortality was modified by cancer type. The effect of statin use was largest for breast and colorectal cancer. Metformin usage in a subpopulation of oral antidiabetic users was in general associated with lower mortality, but this association was modified by cancer type. The association was strongest for liver, colorectal and breast cancer.

Prasugrel as opposed to clopidogrel improves endothelial nitric oxide bioavailability and reduces platelet-leukocyte interaction in patients with unstable angina pectoris: A randomized controlled trial

BackgroundPlatelet inhibition has been linked to improved endothelial function, a prognostic factor in coronary artery disease. Whether prasugrel, a potent platelet inhibitor, affects endothelial function remains unknown. MethodsThis was a double-blind, randomized, active-controlled, parallel trial. Patients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) received either a daily dose of clopidogrel 75mg (n=23) or prasugrel 10mg (n=22). Flow-mediated dilation (FMD), circulating nitrate and nitrite, inflammatory markers and platelet-leukocyte aggregates (PLAs) were assessed the day after PCI and after 3months. ResultsBaseline patient demographics were well matched between treatment groups. Prasugrel led to a significant improvement of FMD after 3months (9.01±3.64% vs. 6.65±3.24%, p=0.001). In contrast, no significant change was observed in the clopidogrel group (7.21±2.84% vs. 6.30±2.97%, p=0.187). Adjusted for baseline FMD, hyperlipidemia and statin use, the treatment effect on change in FMD favoured prasugrel by an absolute 1.97% (95% CI 0.29% to 3.66%, p=0.023). A significant reduction of plasma hsCRP, myeloperoxidase and neutrophil elastase and an increase of nitrate levels were noted in both treatment arms. Interestingly, only prasugrel significantly reduced sCD40 ligand and RANTES and increased nitrite levels. Prasugrel reduced the ADP-stimulated increase in PLAs by 40% (IR: 82 to 13), whereas clopidogrel revealed no such effect (1% increase (IR: 13 to 50) (p=0.01). ConclusionPrasugrel exhibits beneficial mid-term effects on endothelial nitric oxide bioavailability and inflammatory markers. (EudraCT number: 2009-015406-19).

RE: Influence of Statins and Cholesterol on Mortality Among Patients With Pancreatic Cancer.

Background Recent studies have suggested associations between statins and enhanced survival among patients with pancreatic ductal adenocarcinoma (PDAC). However, the relationship between statins, cholesterol, and survival remains unclear. Methods We conducted a retrospective cohort study on 2142 PDAC patients in a regional integrated healthcare system from 2006 to 2014. Electronic pharmacy records were used to abstract information on the type, length, and dosage of statin exposures starting in the year prior to diagnosis. The cumulative and individual effects of simvastatin, lovastatin, atorvastatin, pravastatin, and rosuvastatin on mortality were assessed using Cox proportional hazards regression. Statins were evaluated as any use (pre- and postdiagnosis as a time-dependent variable) and baseline use (prediagnosis only). We also evaluated whether low-density lipoprotein (LDL) cholesterol, measured at various time windows prior to diagnosis, had an independent influence on survival. Additional analyses were performed to examine whether cholesterol mediated the relationship between statins and mortality. All models included age, race, stage, surgery, gemcitabine-based chemotherapy, and the Charlson comorbidity index as covariates. Results Any (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.79 to 0.97) and baseline (HR = 0.88, 95% CI = 0.79 to 0.98) statin use were both associated with a decreased risk in mortality. When assessing individual statins, we found reduced mortality among simvastatin (HR = 0.87, 95% CI = 0.77 to 0.98) and atorvastatin (HR = 0.58, 95% CI = 0.46 to 0.72) users. Cholesterol was not associated with mortality and did not mediate any relationships between statins and survival. Conclusions Statin use rather than cholesterol level was associated with lower mortality risk in patients with pancreatic cancer. Statins appear to improve survival through a lipid-independent mechanism.

Relation of Exercise Capacity to Risk of Development of Diabetes in Patients on Statin Therapy (the Henry Ford Exercise Testing Project)

High exercise capacity (EC) has been associated with a lower risk of incident diabetes, whereas statin therapy has been associated with a higher risk. We sought to investigate whether the association between EC and diabetes risk is modified by statin therapy. This retrospective cohort study included 47,337 patients without diabetes or coronary artery disease at baseline (age 53 ± 13 years, 48% women, 66% white) who underwent clinical treadmill stress testing within the Henry Ford Health System from January 1, 1991, to May 31, 2009. The patients were stratified by baseline statin use and estimated peak METs achieved during exercise testing. Hazard ratios for incident diabetes were calculated using Cox proportional hazards models adjusted for demographic characteristics, co-morbidities, pertinent medications, and stress test indication. We observed 6,921 new diabetes cases (14.6%) over a median follow-up period of 5.1 years (interquartile interval of 2.6 to 8.2 years). Compared with the statin group, the no-statin group achieved higher mean METs (8.9 ± 2.7 vs 9.6 ± 3.0, respectively; p <0.001). After adjustment for covariates, a higher EC was associated with a lower risk of incident diabetes, irrespective of statin use (p-interaction = 0.15). Each 1-MET increment was associated with an 8%, 8%, and 6% relative risk reduction in the total cohort, the no-statin, and the statin groups, respectively (95% confidence interval, 0.91 to 0.93, 0.91 to 0.93, and 0.91 to 0.96, respectively; p <0.001 for all). We conclude that a higher EC is associated with a lower risk of incident diabetes regardless of statin use.