Concomitant Use Of Statins Research Articles

Combination of statin/vitamin D and metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of two randomized clinical trials.

6617 Background: Retrospective database studies have suggested that statins and vitamin D have a positive impact on prostate cancer survival and specifically in mCRPC patients (pt). Methods: We conducted a post-hoc analysis of individual pt data of mCRPC pts treated with abiraterone (AA) and/or Prednisone (P) on two randomized phase III clinical trials COU -AA-301 and COU-AA-302 to analyze the impact of statins and vitamin D in overall survival (OS). Statistical analyses were performed using the Kaplan Meier method and Independent predictors were investigated using Cox regression analysis. This study, carried out under YODA Project #2016-1136, used data obtained from the Yale University Open Data Access Project. Results: These two studies included 2280 patients (1340 treated with AA/P and 640 with P). Use of Statin + vitamin D was associated with a 38% reduction in mortality in the postdocetaxel setting and 32% in the predocetaxel setting in patients treated with abiraterone (Table 1 and 2). No significant reduction in the rate of skeletal-related events was seen in patients treated with vitamin D or statins. Conclusions: To our knowledge this is the first report suggesting the impact of vitamin D+statin in mCPRC treated with abiraterone. The potential benefits of vitamin D do not seem to be secondary to concomitant statin use in this population. Further studies are needed to confirm these results. [Table: see text][Table: see text]

Cardioprotective Effect of Statins in Patients With HER2-Positive Breast Cancer Receiving Trastuzumab Therapy

BackgroundStatins can reduce the risk of anthracycline-induced cardiotoxicity. Whether such cardioprotective effects can be seen in trastuzumab-treated patients has not been explored. MethodsConsecutive women with HER2+ breast cancer who received trastuzumab with or without anthracyclines were identified retrospectively. Patients receiving statins before and during cancer treatment were matched with 2 patients of the same age (± 2 years) and anthracycline exposure status but without statin treatment. The primary outcome was final left ventricular ejection fraction (LVEF). Analysis of covariance (ANCOVA) was used to assess the relationship between statin exposure and the final LVEF. A logistic regression model was constructed to assess the relationship between statin exposure and cardiotoxicity (secondary outcome). ResultsIncluded were 129 patients (62 ± 9 years). Forty-three received statins during cancer treatment. The median trastuzumab exposure time was 11.8 (interquartile range [IQR] 11 to 12) months. Seventy-two (56%) patients received anthracyclines. Compared with controls, patients treated with statins were more likely to have diabetes (37.2% vs 4.7%, P < 0.001), hypertension (58.1% vs 22.1%, P < 0.001), and coronary artery disease (11.6% vs 2.3%, P = 0.04). Within a median cardiac follow-up duration of 11 (IQR 9 to 18) months, the adjusted final LVEF was lower in the control group (61.2% vs 64.6%, P = 0.034). A significant change in LVEF was observed in the control group (median –6%, IQR –10% to –1% P < 0.001) but not in the statin group (median 0%, IQR –5% to +3%, P = 0.27). Upon adjusted analysis, statin treatment was independently associated with a lower risk of cardiotoxicity (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.10-0.99, P = 0.049). ConclusionsIn women with HER2+ breast cancer receiving trastuzumab-based therapy with or without anthracyclines, concomitant use of statins was associated with a lower risk of cardiotoxicity.

Impact of Concomitant Use of Beta blocker, Statin, Aspirin, and Metformin on Central Hemodynamics and Arterial Stiffness in Hypertension

Objective: To assess the impact of concomitant use of aspirin, BB (metoprolol), statin (atorvastatin), and metformin on central haemodynamics and arterial stiffness parameters in treated hypertensive patients. Materials and Methods: We did a cross-sectional study on 476 treated hypertensives. Oscillometric PWA was accomplished by Mobil-o-Graph (IEM, Germany) and groups were stratified using low-dose aspirin, statin, BB, or metformin. Parameters studied were brachial hemodynamics (BP, heart rate, and rate pressure product), arterial stiffness (augmentation pressure, augmentation index, pulse wave velocity, total arterial stiffness, and pulse pressure amplification), and central hemodynamics (central BP, cardiac output, and stroke work). Results: All pairs were matched by or comparable for major confounding factors except concomitant use of drugs. The use of BB, aspirin, and statin had favorable effect on brachial and central hemodynamics. Metformin use had effect more on central than brachial hemodynamics. BB and metformin had negative, statin had indifferent, and aspirin had positive effect on arterial stiffness. Only few of these differences had statistical significance. Frequency of central pulse pressure ≥40 was insignificantly affected by drugs studied. Conclusions: Concomitant aspirin, BB, and metformin in hypertensives have favorable effects on hemodynamics, brachial more than central. Arterial stiffness has positive impact of metformin and negative impact of BB use. These effects must be considered in studies focusing hypertensive therapies. It remains inconclusive whether these results are due to drugs or their indication.

Characteristics and Outcomes of Ibrutinib-Associated Musculoskeletal Toxicities in CLL Patients

Characteristics and Outcomes of Ibrutinib-Associated Musculoskeletal Toxicities in CLL Patients

Concomitant use of statins and macrolide antibiotics and risk of serious renal events: A nationwide cohort study

BackgroundConcomitant use of statins metabolized by the cytochrome P450 isoenzyme 3A4 (CYP3A4) and CYP3A4-inhibiting macrolide antibiotics may confer an increased risk of renal failure. We investigated the risk of serious renal events associated with concomitant use of such statins and such macrolides. MethodsIn a nationwide register-based cohort study (Denmark, 1999–2017), we identified 906,423 new users (40–79 years old), of CYP3A4-metabolized statins. In propensity score-matched analyses, we compared the risk of serious renal events during episodes of concomitant use of statins and CYP3A4-inhibiting macrolides (n = 71,521) with episodes of use of statins alone (n = 285,488) and, as the primary analysis, with episodes of concomitant use of statins and an active comparator (penicillin V, n = 139,446). Using proportional hazards regression, we estimated hazard ratios (HRs) for serious renal events within 30 days of start of follow-up. ResultsWe observed 25 serious renal events during concomitant use of statins and macrolides (incidence rate [IR], 4.9 per 1000 person-years). Compared with use of statins alone (50 events; IR, 2.3), concomitant use of statins and macrolides was associated with a significantly increased risk of serious renal events (HR 2.16, 95% confidence interval [CI] 1.33, 3.49). Compared with concomitant use of statins and penicillin V (52 events; IR, 5.3), however, we observed no increased risk (HR 0.93, 95% CI 0.58, 1.49). ConclusionsIn this nationwide cohort study concomitant use of statins and macrolides was not associated with a significantly increased risk of serious renal events.

The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins.

Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.

Longitudinal study of short-term corticosteroid use by working-age adults with diabetes mellitus: Risks and mitigating factors.

This study assessed the frequency of short-term oral corticosteroid use in adults with diabetes, examined the incidence of fractures, venous thromboembolism (VTE), and hospitalization for sepsis after corticosteroid use, and evaluated whether preventative medications mitigated adverse events. A longitudinal study (2012-14) was conducted of 1 548 945 adults (aged 18-64 years) who received healthcare coverage through a large national health insurer. Incidence rate ratios (IRR) were calculated using conditional Poisson regression. Short-term oral corticosteroids were used by 23.9%, 20.8%, and 20.9% of adults with type 2 diabetes, type 1 diabetes, and no diabetes, respectively, during the 3-year period (P < 0.001). Baseline risks of fracture, VTE, and sepsis were greater for individuals with than without diabetes (P < 0.001). The combined effect of having diabetes and using corticosteroids was greater than the sum of the individual effects (synergy indices of 1.17, 1.23, 1.30 for fracture, VTE, and sepsis, respectively). The IRR for VTE in the 5-30 days after corticosteroid use was 3.62 (95% confidence interval [CI] 2.41-5.45). Fractures increased in the 5-30 days after corticosteroid use (IRR 2.06; 95% CI 1.52, 2.80), but concomitant use of ergocalciferol mitigated this risk (IRR 1.13; 95% CI 0.12, 11.07). The risk of hospitalization for sepsis was elevated with corticosteroid use (IRR 3.79; 95% CI 2.05, 7.01), but was mitigated by the concomitant use of statins. Short-term oral corticosteroid use is common in adults with diabetes and is associated with an elevated, but low, risk of adverse events. The findings suggest that preventative medications may mitigate risk.

Maintenance use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk.

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may have a preventive effect against prostate cancer. However, evidence is limited and still controversial, especially considering non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). Swedish nationwide population-based cohort study including all long-term (≥180 days) adult male users of aspirin (n = 419,931) or NSAIDs (n = 223,437) followed from the first dispense date until the first cancer diagnosis, death or 31 December 2012, whichever occurred first. The risk of prostate cancer was measured as standardized incidence ratios (SIR) and 95% confidence intervals (CI), assessing duration of use, age and concomitant statins intake, comparing to the general male background population of the same age in Sweden. The overall SIR suggests that maintenance use of aspirin decreases the risk of prostate cancer (SIR = 0.87, 95% CI 0.85-0.88), in particular if used ≥5 years (SIR = 0.31, 95% CI 0.30-0.32). The overall risk was decreased (SIR = 0.87, 95% CI 0.85-0.90) among other NSAIDs users, and again in particular among longer-term users (≥3 years) with SIR = 0.58 (95% CI 0.53-0.63). When statins users were excluded from all aspirin users, there was no remaining association with prostate cancer (SIR = 0.99, 95% CI 0.96-1.02), only if taken ≥5 years (SIR = 0.31, 95% CI 0.29-0.34). For non-aspirin NSAIDs users, the protective effect remained after exclusion of statins users (SIR = 0.92, 95% CI 0.88-0.95). This population-based cohort study provides evidence for a protective effect of aspirin and other NSAIDs against prostate cancer, in particular for longer durations of use, yet concomitant use of statins strongly influences the risk among aspirin users.

Exclusive and Combined Use of Statins and Aspirin and the Risk of Pancreatic Cancer: a Case-Control Study

Data on the association between aspirin and statin use and Pancreatic Ductal AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed, but no studies evaluated the potential combined or confounding effect of the two at the same time. We aimed to investigate the association between aspirin and statin exclusive and combined use and PDAC occurrence. Data on environmental factors, family and medical history were screened in a case-control study. PDAC cases were matched to controls for age and gender. Power calculation performed ahead. Odds ratios (OR) and 95% confidence intervals(CI) were obtained from multivariable logistic regression analysis. In 408 PDAC patients and 816 matched controls, overall statin (OR 0.61; 95%CI,0.43–0.88), but not aspirin use was associated to reduced PDAC risk. Compared to non-users, exclusive statin (OR 0.51; 95%CI,0.32–0.80) and exclusive aspirin users (OR 0.64; 95%CI,0.40–1.01) had reduced PDAC risk. Concomitant statin and aspirin use did not further reduce the risk compared with statin use alone and no interaction was evident. Statin protective association was dose-dependent, and consistent in most subgroups, being stronger in smokers, elderly, obese and non-diabetic patients. The present study suggests that statin use is associated to reduced PDAC risk, supporting a chemopreventive action of statins on PDAC.

Alirocumab Treatment and Achievement of Non-High-Density Lipoprotein Cholesterol and Apolipoprotein B Goals in Patients With Hypercholesterolemia: Pooled Results From 10 Phase 3 ODYSSEY Trials.

BackgroundNon‐high‐density lipoprotein cholesterol (non‐HDL‐C) and apolipoprotein (apo) B are better predictors of atherosclerotic cardiovascular disease risk than low‐density lipoprotein cholesterol alone. US and European lipid management guidelines support non‐HDL‐C and apoB as targets for lipid‐lowering therapy.Methods and ResultsThis analysis evaluated the efficacy of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, on non‐HDL‐C and apoB. Data were derived from 4983 patients enrolled in 10 randomized, placebo‐ or ezetimibe‐controlled Phase 3 ODYSSEY trials. Primary end point for this pooled analysis was percent reduction in non‐HDL‐C and apoB at Week 24; secondary end points included the percentage of patients achieving guideline‐directed treatment goals (National Lipid Association guidelines: non‐HDL‐C <100 or <130 mg/dL for patients at very high and high cardiovascular risk, respectively; European Society of Cardiology/European Atherosclerosis Society guidelines: apoB <80 mg/dL for patients at very‐high cardiovascular risk). Data were grouped according to comparator, alirocumab starting dose, and concomitant statin use. Compared with controls, alirocumab produced significantly greater reductions in non‐HDL‐C and apoB at Week 24 (P<0.0001), an effect extending up to 78 weeks. More alirocumab‐treated patients achieved levels of non‐HDL‐C <100 mg/dL and apoB <80 mg/dL (P≤0.0001 versus control). By Week 24, >70% of alirocumab‐treated patients on background statin achieved non‐HDL‐C <100 or <130 mg/dL, and apoB <80 mg/dL. Safety was comparable across pooled groups and in line with previous reports.ConclusionsAlirocumab produced significant, sustained reductions in non‐HDL‐C and apoB, allowing more patients to achieve lipid goals compared with placebo or ezetimibe and irrespective of maximally tolerated statin use.

A Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development.

Bococizumab (RN316/PF-04950615), a humanized monoclonal antibody, binds to secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) and prevents its downregulation of low-density lipoprotein receptor, leading to improved clearance and reduction of low-density lipoprotein cholesterol (LDL-C) in plasma. A mechanism-based drug-target binding model was developed, accounting for bococizumab, PCSK9, and LDL-C concentrations and the effects of concomitant administration of statins. This model was utilized to better understand the pharmacokinetic/pharmacodynamic (PK/PD) data obtained from 3 phase 1 and 2 phase 2a clinical studies. First, simulations performed with this model demonstrated that the conventional method of the area-under-the-curve ratio for bioavailability determination underestimated the subcutaneous bioavailability of bococizumab due to its target-mediated disposition. Second, a covariate model component for statin effects on bococizumab PK/PD was characterized, including a description of the decreased baseline LDL-C, increased baseline PCSK9, and increased LDL-C lowering with concomitant use of statins. Last, the impact of the dosing regimens with and without a dose holiday on bococizumab's LDL-C-lowering effectiveness was shown to be predictable due to the well-characterized PK-PD relationship.

The association of antidepressant and statin use with death and incident cardiovascular disease varies by depression severity

Depression has been reported to be associated with a greater risk of death and cardiovascular disease (CVD); however, the impact of antidepressants (ADM) on CVD risk remains controversial. Statin use is known to decrease CVD risk. Whether the use of these medications together affects CVD risk has not been studied. Patients (N = 26,828) completing the patient health questionnaire (PHQ-9), ≥40 years of age, without prior CVD, and no prior ADM use were studied. Depressive severity was categorized as none-mild (PHQ-9 score ≤14, n = 21,517) and moderate-severe (PHQ-9 score ≥15, n = 5311). Cox hazard regression was used to evaluate the association of no ADM/no statin use (n = 23,104 [86.1%]), ADM/no statin use (n = 877 [3.3%]), no ADM/statin use (n = 2627 [9.8%]), and ADM/statin use (n = 220 [.8%]) with major adverse cardiovascular events (MACE: death, CAD, stroke). Patients averaged 56 ± 12 years; 61% female. There were 1182 (4.4%) 3 year MACE events. The association of ADM and statin use with MACE varied by depressive symptom severity, with statin therapy associated with a decreased risk in the none-mild group (HR = .78, p = .007) and ADM in the moderate-high group (HR = 0.58, p = 0.02). Concomitant use of ADMs and statins did not appear to provide additive benefit.

Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin

ObjectiveThe purpose of this study was to investigate the risk of myopathy when statins are coadministered with colchicine in patients with gout. MethodsIn gout patients who received colchicine with or without statin, clinical data collected included medications and history of hypertension, chronic kidney disease, and liver cirrhosis. Myopathy was defined as the presence of muscle symptoms with elevated creatine kinase or myoglobin. Multivariate analysis was performed to identify risk factors for myopathy. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to evaluate the influence of concomitant colchicine and statin use on myopathy. ResultsOf 674 patients, 486 received colchicine alone and 188 also received statin. The incidence of myopathy was not significantly higher in those on both drugs than in those on colchicine alone (2.7% vs 1.4%, P = .330). On multivariate analysis, chronic kidney disease (hazard ratio [HR] 29.056; 95% confidence interval [CI], 4.387-192.450; P <.001), liver cirrhosis (HR 10.676; 95% CI, 1.279-89.126; P = .029), higher colchicine dose (HR 20.960; 95% CI, 1.835-239.481; P = .014), and concomitant CYP3A4 inhibitor (HR 12.027; 95% CI, 2.743-52.725; P = .001) were associated with increased risk of myopathy. Concomitant use of statins, however, was not, even after adjusting for confounders (HR 1.123; 95% CI, 0.262-4.814; P = .875; IPTW-adjusted HR 0.321; 95% CI, 0.077-1.345; P = .120). ConclusionConcomitant use of statin and colchicine was not associated with increased risk of myopathy. Thus, concomitant use of statin with colchicine seems to be safe from myotoxicity in gout patients.

Platelet reactivity and clinical outcomes in patients using CYP3A4-metabolized statins with clopidogrel in percutaneous coronary intervention.

Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Recent studies suggest that CYP3A4-metabolized statins attenuate clopidogrel's anti-aggregatory effect on platelets. We aimed to assess the impact of concomitant CYP3A4-metabolized statin and clopidogrel use on antiplatelet activity and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We enrolled 1187 patients from the HOST-ASSURE trial with platelet reactivity unit (PRU) values at both baseline and 1 month. Patients were assigned to the CYP3A4-metabolized statin group (group A, n=725) or non-CYP3A4-metabolized statin group (group B, n=462) according to type of statin used. Co-primary outcomes were the differences between PRU at baseline and 1 month and the composite of cardiovascular death, recurrent myocardial infarction, stent thrombosis, revascularization, and cerebrovascular accident. We found that follow-up PRU values did not change in group A and decreased significantly in group B (mean difference: -15±79, p<0.001) in both the crude and matched cohorts. Patients with a high PRU value at baseline, irrespective of statin type, had a significant reduction in mean PRU difference (group A, -62±78, p<0.001; group B, -59±69, p<0.001) in both the crude and matched cohorts. The composite of clinical events did not differ between groups in either cohort. CYP3A4-metabolized statins slightly inhibit the antiplatelet activity of clopidogrel during dual antiplatelet therapy. However, they do not inhibit clopidogrel's antiplatelet effect in patients with high platelet reactivity or increase clinical events in patients following PCI.

Concomitant Use of Statins in Tocilizumab-Treated Patients with Rheumatoid Arthritis: A Post Hoc Analysis.

IntroductionPatients with rheumatoid arthritis (RA) have decreased survival because of increased cardiovascular risk compared with the general population, and treatment with tocilizumab (TCZ) has been shown to increase lipid levels; however, the relationship between lipids and cardiovascular risk is unknown. This post hoc analysis expanded on previously reported 24-week results by characterizing statin use and subsequent changes in lipid parameters in patients with RA treated with intravenous or subcutaneous TCZ (TCZ-IV or TCZ-SC) over 2 years of treatment.MethodsData were collected from patients with moderate to severe active RA who received ≥1 dose of the study drug in seven international, randomized, double-blind, controlled phase 3 and 4 clinical trials of TCZ-IV or TCZ-SC. Lipid levels and safety events were assessed over 2 years of treatment. Data were summarized for all pooled treatment groups of the intention-to-treat populations in the TCZ-IV and TCZ-SC studies, and results were stratified by concomitant statin use.ResultsData from this descriptive, retrospective, pooled analysis indicated that statins can stabilize lipid levels without a clinically significant increase in adverse events. Approximately 30% of patients in the TCZ treatment arms who never received a statin demonstrated a shift in low-density-lipoprotein cholesterol (LDL-C) from <130 mg/dl at baseline to ≥130 mg/dl at 2 years. However, despite the increased potential cardiovascular risk, <15% of patients with LDL-C ≥100 mg/dl and <35% of patients with a total cholesterol:high-density-lipoprotein cholesterol ratio >5 at 2 years were receiving concomitant statins.ConclusionConcomitant statin use attenuated TCZ-mediated lipid increases; however, a large proportion of TCZ-treated patients potentially at risk of cardiovascular disease were untreated. These findings highlight the need for better understanding of potential risk associated with TCZ-mediated lipid elevations as well as implementation of RA-specific guidelines on the recognition and management of elevated risk of cardiovascular events in patients with RA.FundingF. Hoffmann-La Roche, Ltd.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-016-0049-8) contains supplementary material, which is available to authorized users.

Statin and Aspirin Pretreatment Are Associated with Lower Neurological Deterioration and Platelet Activity in Patients with Acute Ischemic Stroke

Aspirin and statin are recommended for the treatment of acute ischemic stroke. However, whether aspirin and statin pretreatment is associated with clinical outcomes has not been well addressed. This study aimed to evaluate the effect of pre-existing statin and aspirin use on platelet activation and clinical outcome in acute ischemic stroke patients. We conducted a prospective, multicenter observational study in patients with acute ischemic stroke. Platelet aggregation and platelet-leukocyte aggregates were measured on admission and during 7-10 days after admission. The primary outcome of the study was neurological deterioration (ND) within 10 days after admission. The secondary outcome was a composite of recurrent ischemic stroke, myocardial infarction, and death during the first 3 months after admission. Physical disability was evaluated using the modified Rankin Scale score at 3 months after admission. Among 1124 enrolled patients, 270 (24%) experienced ND. Higher platelet aggregation and platelet-leukocyte aggregates on admission and during 7-10 days were associated with ND. Platelet aggregation and platelet-leukocyte aggregates on admission were significantly lower in the patients with pre-existing statin or aspirin use than those without treatment. Patients with prestroke concomitant statin and aspirin treatment had significantly lower incidence of ND than those without treatment. Diabetes mellitus, fasting glucose, platelet-leukocyte aggregates, and prestroke concomitant statin and aspirin use were independently associated with ND. Prestroke concomitant statin and aspirin use is associated with lower neurological deterioration and platelet activity in patients with acute ischemic stroke.

A Multisite Review of Concomitant Use of Daptomycin and Statins and the Effect on CPK

A Multisite Review of Concomitant Use of Daptomycin and Statins and the Effect on CPK

Synergistic Benefit of Statin and Metformin in Gastrointestinal Malignancies

Objectives: To evaluate whether statin use influences gastrointestinal cancer prognosis in patients with diabetes mellitus (DM). Methods: We reviewed all DM patients diagnosed at Roswell Park Cancer Institute with emergent gastrointestinal malignancy (January 2003 to December 2010) (N = 222). Baseline demographic, clinical history, and cancer outcomes were documented. Overall survival (OS) and disease-free survival (DFS) comparisons across various treatment groups were assessed by Kaplan-Meier and Cox proportional hazards. Results: Use of statin, alone or in combination, was associated with improved OS and DFS (hazard ratio [HR] = 0.65, P = .06; HR = 0.60, P < .02). We report similar OS and DFS advantage among users of mono- or combined metformin therapy (HR = 0.55, P < .01; HR = 0.63, P < .02). Concomitant use of metformin and statin provided a synergistic OS and DFS benefit (HR = 0.42, P < .01; HR = 0.44, P < .01). Despite significant tobacco and alcohol use history, patients with upper gastrointestinal cancers derived enhanced cancer outcomes from this combination (HR = 0.34, P < .01; HR = 0.43, P < .02), while receiving a statin without metformin or metformin without a statin did not provide significant cancer-related benefits. Conclusion: Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer.

To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n=32), low-grade pathology (n=4), underwent early cystectomy within 3months (n=25), had <3months of follow-up (n=11), or did not receive an induction course of intravesical BCG (n=32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4months. There were 20 (20.2%) deaths, including 6 (6.1%) patients with bladder cancer-related mortality. 13% patients experienced tumor progression and 27% underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65%), aspirin (63%), or non-aspirin NSAIDs/COX inhibitors (26%). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

The Effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study.

Both preclinical studies and clinical trials have indicated that the combination of a selective serotonin reuptake inhibitor (SSRI) and a statin may have superior antidepressant effects compared with SSRI treatment alone. The authors sought to assess whether this beneficial effect can be generalized to a more heterogeneous population of SSRI users. In a nationwide cohort study that included all incident SSRI users in Denmark between 1997 and 2012, the authors compared people who had periods of concomitant use of SSRIs and statins with people who had periods of SSRI treatment alone. Outcomes included the rates of psychiatric hospital contacts (any cause), psychiatric hospital contacts due to depression, suicidal behavior, and all-cause mortality. Using Cox regression and competing risk analysis, the authors calculated crude and adjusted hazard ratios for these outcomes. The authors identified 872,216 incident SSRI users, of whom 113,108 (13.0%) used a statin concomitantly. Compared with SSRI treatment alone, the combined use of an SSRI and a statin was associated with a significantly lower risk for both psychiatric hospital contacts (adjusted hazard ratio=0.75 (95% CI=0.69, 0.82) and psychiatric hospital contacts due to depression (adjusted hazard ratio=0.64, 95% CI=0.55, 0.75). Compared with SSRI treatment alone, the concomitant use of SSRIs and statins was not associated with significant increases in all-cause mortality (adjusted hazard ratio=1.04, 95% CI=0.96, 1.12) or suicidal behavior (adjusted hazard ratio=0.85, 95% CI=0.61, 1.18). In a large naturalistic cohort, concomitant treatment with SSRIs and statins resulted in robust advantages compared with SSRIs alone.