Concomitant Use Of Statins Research Articles

The effect of statins on the outcome of Clostridium difficile infection in hospitalized patients.

Several studies have shown an association between exposure to statins and favorable clinical outcomes for various types of infections. We aimed to assess the impact of statin use on mortality, disease severity and complications among hospitalized patients with Clostridium difficile infection (CDI). Data were analyzed from a retrospectively collected database of 499 patients diagnosed with CDI during 2009-2014. We compared infection outcomes between 178 statin (36 %) users and 321 (64 %) non-users. On multivariate analysis, we found that statin use did not have a significant impact on 30-day mortality (OR = 1.54; 95 % CI, 0.85-2.79; p = 0.15) or any significant effect on CDI severity and complication. Concomitant statin use has no significant impact on short-term mortality or effect on CDI severity and complications among hospitalized patients with CDI. However, patients in the statin group were older and had higher Charlson score compared with the non-statin group. Whether these factors affected a possible impact of statins on the disease course remains to be investigated. • Clostridium difficile is the most common cause of infectious nosocomial diarrhea among hospitalized adult patients in the developed countries. • There is an increasing morbidity and mortality of CDI patients due to the emergence of new strains of high virulence. • Recent studies demonstrated that prior statin use has protective and ameliorating effects on morbidity and mortality among CDI patients. • Our study showed that concomitant statin use has no significant impact on short-term mortality, CDI severity and its complications.

Clopidogrel-statin interaction: A missing links

Introduction: The use of clopidogrel is associated with a large variability in the response to this drug, wherein the results of the numerous studies indicate that even one out of three patients can be placed in the category of non responder. Corresponding section headings: Among the many causes of modified pharmacodynamic effects of clopidogrel, special attention is addressed to the possible clopidogrel-statin interaction. Numerous studies have focused on this problem, but it still seems to be missing the right answer. Conclusion: This paper reviews some of the most important facts regarding concomitant use of clopidogrel and statins, and specific issues to be addressed for safe treatment of patients.

Concomitant use of statins and s-(2-boron-ethyl)-l-cysteine arginase inhibitor to correct endotoxin-induced endothelial dysfunction

The concomitant use of non-selective S-(2-boron-ethyl)-L-cysteine (BEC) arginase inhibitor with simvastatin, atorvastatin, rosuvastatin and nanoparticulated rosuvastatin on the background of endotoxin-induced disorder modeling by Staphylococcus aureus (strain 13407) injection under the skin – 60 billions of microbial bodies – exhibits an endothelium- and cardio-protective action which is evident as endothelial dysfunction factor (EDF) increase prevention, adrenoreactivity, maintenance of myocardial reserve, and normalization of biochemical markers (total NO, expression of eNOS, C-reactive protein, IL-6, tumor necrosis factor). However, the concomitant therapy has shown no additive action of medications.

Mortality in Individuals Treated With Glucose-Lowering Agents: A Large, Controlled Cohort Study.

Several observational studies and meta-analyses have reported increased mortality of patients taking sulfonylurea and insulin. The impact of patient profiles and concomitant therapies often remains unclear. The objective of the study was to quantify survival of patients after starting glucose-lowering agents (GLAs) and compare it with control subjects, matched for risk profiles and concomitant therapies. This was a retrospective, controlled, cohort study. The study is based on health expenditure records of the largest Belgian health mutual insurer, covering more than 4.4 million people. A total of 115 896 patients starting metformin, sulfonylurea, or insulin (alone or in combination) between January 2003 and December 2007 participated in the study. Control subjects without GLA therapy were matched for age, gender, history of cardiovascular events, and therapy with antihypertensives, statins and blood platelet aggregation inhibitors. There were no interventions. Five-year survival after the start of GLA was measured. Profiles of patients using different GLAs varied, with patients on sulfonylurea being oldest and patients on insulin having more frequently a history of cardiovascular disease. Excess mortality differed across GLA therapies compared with matched controls without GLAs, even after adjusting for observable characteristics. Only metformin monotherapy was not associated with an increased 5-year mortality compared with matched controls, whereas individuals on a combination of sulfonylurea and insulin had the highest mortality risks. Age and concomitant use of statins strongly affect survival. Differences exist in 5-year survival of patients on GLA, at least partly driven by the risk profile of the individuals themselves. Metformin use was associated with lowest 5-year mortality risk and statins dramatically lowered 5-year mortality throughout all cohorts.

Abstract 17525: Warfarin Promotes Progressive Coronary Arterial Calcification: Insights From Serial Intravascular Ultrasound

Background: Warfarin blocks the synthesis and activity of matrix Gla protein (MGP), a vitamin K-dependent inhibitor of arterial calcification. The impact of warfarin on coronary arterial calcification in vivo is unknown. This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients treated with and without warfarin. Hypothesis: Serial changes in coronary CaI are greater in warfarin-treated patients compared with those not on warfarin, independent of changes in PAV Methods: In a patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound, we compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease treated with (n=171) and without (n=4129) warfarin during an 18-24-month period. Results: Patients (age 57.9±9.2 yrs; male 73%; prior and concomitant statin use: 73 and 97% respectively) demonstrated an overall increase in PAV by 0.18±0.06% (p=0.003 compared with baseline) and CaI [median (IQR)] by 0.04 (0.00, 0.11) (p <0.001 compared with baseline). Following propensity-weighted adjustment for clinical trial, clinical characteristics and laboratory parameters, there was no difference in annualized ΔPAV in the presence and absence of warfarin treatment (0.08±0.05 vs. 0.13±0.04%, p=0.41). Following adjustment for PAV, a greater annualized increase in CaI was observed in warfarin treated patients [median (IQR) 0.03 (0.0-0.08) vs. no-warfarin: 0.02 (0.0-0.06) p<0.001)]. In a sensitivity analysis evaluating a 1:1 matched cohort (n=164 per group), significantly greater annualized changes in CaI were also observed in warfarin-treated patients. In a multivariable model, warfarin independently associated with an increasing CaI [Odds Ratio (95% confidence interval) 1.12 (1.01, 1.24), p=0.027]. Conclusion: Warfarin therapy associates with progressive coronary atheroma calcification, independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes require further investigation.

PDB1 - Risk of New-Onset Diabetes Associated with Concomitant Antidepressant, Inhaled Corticosteroids, and Statin Use Among Medicaid Beneficiaries with COPD

PDB1 - Risk of New-Onset Diabetes Associated with Concomitant Antidepressant, Inhaled Corticosteroids, and Statin Use Among Medicaid Beneficiaries with COPD

Statin and the risk of hepatocellular carcinoma and death in a hospital-based hepatitis B-infected population: A propensity score landmark analysis

The use of statin in hepatocellular carcinoma (HCC) and death prevention is still uncertain among hepatitis B infected (HBV) patients. This study aimed to examine the effect of statin on HCC and death in a HBV population. We conducted a hospital-based population study of HBV patients, using the Hospital Authority database in Hong Kong. We defined statin use by landmark analysis to abrogate "immortal time bias" and propensity score (PS) weighting to minimize baseline confounders and "indication bias". Multiple imputations for missing data were performed. The weighted Cox regression analyses was performed for the risk of HCC (adjusting for competing mortality) and death. A total of 73,499 patients with a crude HCC incidence of 1.75 per 100 patient-years were entered into the 2-year landmark analysis. After landmark analysis and PS weighting of baseline covariates, statin users had a 32% risk reduction in HCC (weighted sub-hazard ratio (SHR) 0.68; 95% CI 0.48-0.97) compared to non-users. There was no decreased risk of death in statin users (weighted HR 0.92; 0.76-1.11, p=0.386). In subgroup analysis, concurrent statin and nucleos(t)ide analogue (NA) use was associated with 59% risk reduction in HCC (weighted SHR 0.41; 0.19-0.89, p=0.023) compared to NA use alone. In this HBV cohort adjusted for confounders and biases, statin use is associated with reduced HCC risk by 32%. Additive HCC chemopreventive effect was seen with the concomitant use of NA and statin. Further prospective studies are warranted to investigate the potential use of statin in NA users.

Proton pump inhibitors are associated with lower gastrointestinal tract bleeding in low-dose aspirin users with ischaemic heart disease

BackgroundImpact of acid suppressants on lower gastrointestinal bleeding remains unclear in low-dose aspirin users; we aimed to investigate this relationship. MethodsRetrospective cohort study of low-dose aspirin users who underwent coronary angiography for ischaemic heart disease in our institution between October 2005 and December 2006; patients were evaluated for upper or lower gastrointestinal bleedings within 3 years post-angiography. Results538 patients were enrolled (males, 74.4%; mean age 67.4±10.6 years). Risk for upper gastrointestinal bleeding decreased with concomitant use of statins (HR, 0.37; 95% CI, 0.15–0.89), calcium channel blockers (HR, 0.29; 95% CI, 0.10–0.85), and histamine-2 receptor antagonists (HR, 0.26; 95% CI, 0.08–0.89). Concomitant use of proton pump inhibitors tended to decrease risk of upper gastrointestinal bleeding (HR, 0.27; 95% CI, 0.06–1.18). Risk for lower gastrointestinal bleeding increased with both concomitant use of warfarin (HR, 15.68; 95% CI, 4.43–55.53) and proton pump inhibitors (HR, 6.55; 95% CI, 2.01–21.32), but not with histamine-2 receptor antagonists. Hyperuricemia lowered risk for lower gastrointestinal bleeding (HR, 0.12; 95% CI, 0.02–0.88). ConclusionsIn low-dose aspirin users, concomitant use of proton pump inhibitors increased lower gastrointestinal bleeding risk, independent from effects on upper gastrointestinal bleeding.

LP18 : Obeticholic acid for NASH: benefits in a high risk subgroup and the effects of concomitant statin use

of cirrhosis is highly desirable because it simplifies post-LT management. Material and Methods: In this adaptive open-label, prospective randomized phase III North American clinical trial (Study 988, NCT01804829) conducted in 2 parts, any antiviral therapy (AVT) pre-LT (resulting in RNA <100 IU/ml prior to transplant) is followed in the active treatment arms by Hepatitis C Immune Globulin (HCIG, Civacir) periand post-LT to prevent HCV infection after LT. In part I (dose finding), patients were randomized 1:1:1 to active (200 or 300mg/kg) or control arms. Active group patients received 16 infusions of Civacir in the periand immediate post-LT period for 10 weeks. Control patients received standard of care (no treatment) immediately after LT. The primary endpoint is sustained virologic response SVR12. Results: Three quarters (N=63 as of 27 Jan 2015) of 84 planned patients have been enrolled. Preliminary efficacy evaluations justified continued enrollment in the 300mg/kg arm but not in the 200mg/kg low dose arm (closed by amendment). Treatment and control arms are comparable at baseline. Mean age of patients is 61 and 84% are male. 93% of patients were treated with sofosbuvirbased regimens pre-LT, for a median duration of 63.5 days including 9.4% with treatment <4 weeks. To date, 1/21 (5%) reinfection was observed in the 300mg/kg arm. In the control and 200mg/kg arm 7/22 (32%) and 6/20 (30%) reinfections occurred, respectively. At day 6, 14, 21 and 28 post-LT the median anti-HCV antibody titer was 440, 312, 274 and 215 U/ml in the 300mg/kg and 39, 44, 53 and 63 U/ml in the control arm. Civacir has been well tolerated with no drug-related serious adverse events to date. The most frequent reported AEs were those well-known for human immunoglobulins, underlying disease, and surgical associated events.

Sustained virologic response and other potential genotype-specific roles of statins among patients with hepatitis C-related chronic liver diseases

While statins have shown antiviral effects in different studies, few data are available about their effect among different HCV genotypes. To evaluate the effect of concomitant statin use on sustained virologic response (SVR) and other treatment outcomes among patients with HCV genotypes 1-3. Using US Department of Veterans Affairs database, multivariate (MV), propensity score matched (PSM) and repeated measures mixed model analyses were performed on patients who received combination therapy with Peg-IFN and Ribavirin for treatment of HCV genotypes 1-3 between October 2001-December 2011. Concomitant statin users were matched with non-users in each genotype and SVR rates were compared. Changes in serum ALT during treatment was assessed. Of 37,611 treated patients, 236 genotype 1 (GT1), 78 genotype 2 (GT2) and 23 genotype 3 (GT3) statin users and non-users were used for PSM. SVR among GT1 patients was 22.8% (overall), significantly higher among statin users (26.3% vs. 19.5% P<0.01 from PSM; OR=1.49 CI 1.06-2.08 P=0.02 from MV). No significant impact of statin use was observed among GT2 (overall SVR - 55.8%, statin users vs. non-users - 53.9% vs. 57.7%, P=0.32), and GT3 (overall SVR - 58.7%, statin users vs. non-users - 60.9% vs. 56.2%, P=0.39) patients. Higher baseline LDL was positively associated with SVR while statin use reduced ALT during treatment in GT1 patients. In view of additional benefits of statins, and the prohibitive cost of newer HCV therapies, statins could be a potential assist for hard-to-treat GT1 patients especially in resource-poor settings.

Potential association between rosuvastatin use and high atazanavir trough concentrations in ritonavir-treated HIV-infected patients.

Emerging evidence shows that standard atazanavir (ATV) dosages are associated with considerable interindividual variability in plasma drug concentrations. Given the potential impact of ATV exposure on clinical outcome, in this retrospective study we sought to assess demographic and clinical factors influencing ATV plasma concentrations in a large cohort of HIV-infected patients. HIV-infected patients treated with ATV for at least 3 months and with at least one assessment of ATV trough concentrations were enrolled. Blood trough samples were collected from all patients immediately before the next drug intake. Plasma ATV and ritonavir concentrations were quantified by a validated chromatographic method coupled with tandem mass spectrometric detection. Univariate and multivariate regression analyses were performed using ATV plasma concentrations as the dependent variable, with demographic and clinical characteristics as the independent ones. A total of 273 HIV-infected adult patients were included in the present study. Factors significantly associated with increased ATV concentrations by univariate analysis were ATV dosage, number of concomitant drugs, ritonavir or statin use. However, with multivariate regression analysis, the only factors independently and significantly associated with ATV concentrations were ritonavir use (r=0.291, P<0.0001) and concomitant rosuvastatin therapy (r=0.315, P<0.0001). We found that patients on ATV/ritonavir given rosuvastatin concomitantly have ATV concentrations that exceed the upper therapeutic threshold of 800 ng/ml known to be associated with a high risk of experiencing ATV-related side effects. In agreement with previous findings we confirmed the lack of association between other demographic and clinical characteristics such as age, gender, body weight and ATV exposure.

Predictors of Congestive Heart Failure after Treatment with an Endothelin Receptor Antagonist

The Avosentan on Time to Doubling of Serum Creatinine, End Stage Renal Disease or Death (ASCEND) trial tested the renoprotective effect of the endothelin receptor antagonist avosentan in patients with diabetes and nephropathy, but the study was terminated due to an excess of congestive heart failure (CHF) events in the avosentan arms, likely due to fluid retention. The aim of this study was to identify risk markers of CHF after treatment with avosentan. In a post hoc analysis of the ASCEND trial (N=1392 participants), we assessed which baseline characteristics predicted CHF risk during avosentan treatment. Furthermore, postrandomization changes between baseline and the first available measurement of body weight and hemoglobin were examined as potential clinical indicators of fluid retention for their relationship with CHF development. Relative to placebo, avosentan increased CHF risk (hazard ratio, 2.76; 95% confidence interval, 1.68 to 4.54). The avosentan-related CHF risk was higher with lower baseline cholesterol levels (P interaction=0.003) and concomitant statin use (P interaction=0.06), whereas it was lower with a lower estimated GFR (P interaction=0.04). Patients allocated to avosentan had a median body weight increase of 0.6 kg (interquartile range, 0.0 to 2.0 kg) and a median hemoglobin decrease of 1.4 g/dl (interquartile range, -2.1 to -0.7 g/dl) at the first postrandomization measurement. The body weight increase induced by avosentan was associated with CHF development (P interaction=0.04), whereas hemoglobin decrease was not (P interaction=0.64). The increase in body weight was particularly pronounced in patients with a cardiovascular disease history and in patients using statins. In avosentan-treated patients, body weight increase, but not hemoglobin decrease, was associated with CHF development, indicating that close body weight monitoring could provide an early signal of CHF development in future trials with endothelin receptor antagonists.

The effect of pioglitazone and extended-release niacin on HDL-cholesterol in diabetes patients in a real-world setting

This retrospective study was designed to assess the effects of the combination of pioglitazone and extended-release niacin on the lipid panel, particularly HDL-cholesterol, when used in patients with type 2 diabetes in an endocrinology specialty practice. The electronic medical records of 434 adult patients with type 2 diabetes receiving extended-release niacin and pioglitazone were screened for review. Patients with type 2 diabetes and hyperlipidemia were included for review if they received the combination of pioglitazone at doses ≥15mg/day and extended-release niacin (Niaspan) at doses ≥1000mg/day for ≥6months. Statistical analysis used paired t-tests with p<0.05 as statistically significant. Both ANOVA and the Tukey-Kramer test for multiple comparisons (α=0.05) were also used. A total of 47 patients, 83% were men with average age of 58, met all eligibility criteria for the study. Compared with baseline, a statistically significant increase in HDL-C (+25.13%, p<0.0001) was observed at the conclusion of combination therapy. The HDL-C levels progressively increased with duration of combination treatment, and were not correlated with concomitant statin use. Significant decreases in total cholesterol and triglycerides were detected, and HbA1c decreased 0.84% during combination therapy for all therapies combined. The combination of pioglitazone and extended-release niacin in patients with type 2 diabetes and hyperlipidemia, used in commonly prescribed doses for at least 6months, resulted in statistically significant improvements in HDL-C, total cholesterol, and triglycerides, and did not result in deteriorations in glycemic control.

Effect of concomitant statin use on rituximab treatment for pemphigus and pemphigoid disorders: a case‐based review

Journal of the European Academy of Dermatology and VenereologyVolume 28, Issue 4 p. 520-522 Letter to the Editor Effect of concomitant statin use on rituximab treatment for pemphigus and pemphigoid disorders: a case-based review K. Heelan, K. Heelan Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, CanadaSearch for more papers by this authorS. Knowles, S. Knowles Division of Clinical Pharmacology and Toxicology at Sunnybrook, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada Department of Pharmacology, Sunnybrook Health Sciences Centre, University of Toronto, CanadaSearch for more papers by this authorS. Walsh, S. Walsh Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, CanadaSearch for more papers by this authorN.H. Shear, Corresponding Author N.H. Shear Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada Division of Clinical Pharmacology and Toxicology at Sunnybrook, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, CanadaCorrespondence: N.H. Shear. E-mail: neil.shear@sunnybrook.caSearch for more papers by this author K. Heelan, K. Heelan Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, CanadaSearch for more papers by this authorS. Knowles, S. Knowles Division of Clinical Pharmacology and Toxicology at Sunnybrook, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada Department of Pharmacology, Sunnybrook Health Sciences Centre, University of Toronto, CanadaSearch for more papers by this authorS. Walsh, S. Walsh Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, CanadaSearch for more papers by this authorN.H. Shear, Corresponding Author N.H. Shear Division of Dermatology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada Division of Clinical Pharmacology and Toxicology at Sunnybrook, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, CanadaCorrespondence: N.H. Shear. E-mail: neil.shear@sunnybrook.caSearch for more papers by this author First published: 24 July 2013 https://doi.org/10.1111/jdv.12217Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume28, Issue4April 2014Pages 520-522 RelatedInformation

THU0226 Baricitinib Effects on Serum Cholesterol and Circulating Lipid Particles in a Phase 2B Study in Patients with Rheumatoid Arthritis

BackgroundBaricitinib, a novel oral inhibitor of JAK1/2, was evaluated in a Phase 2b study in patients (pts) with moderate to severe RA. The primary ACR20 12-week endpoint was met, and...

Abstract 275: Concomitant Statin Use With Ezetimibe Or Colesevelam For Treatment Of Hypercholesterolemia

OBJECTIVES: Ezetimibe or colesevelam are often used for treating hypercholesterolemia when statin therapy is insufficient or not well tolerated. Our study objective was to examine prevalence of concomitant statin use and associated factors among hypercholesterolemia patients newly treated with ezetimibe or colesevelam. METHODS: This analysis evaluated a large health plan’s Commercial and Medicare Advantage claims data from 1/1/08 to 7/31/12. The first ezetimibe (excluding fixed combination therapy of ezetimibe/simvastatin) or colesevelam prescription fill date during this period was identified as the index date. Patients were assigned to either ezetimibe or colesevelam cohort based on the index drug and were required to have ≥ 2 consecutive prescriptions for the index drug and have at least 6 months and 12 months continuous enrollment before and after the index date, respectively. Prevalence of concomitant statin use was identified based on pharmacy claims. Patient demographics and clinical characterisitics were explored to examine the factors associated with concomitant statin use using multivariate logistic regression. RESULTS: A total of 679 colesevelam and 1439 ezetimibe patients were included in this study. The concomitant use of statins was 24% among colesevelam and 50% among ezetimibe patients, respectively. After adjustment for patient demographics and comorbidities, ezetimibe patients were 3.2 times more likely than colesevelam patients to have concomitant statin use (OR= 3.168, 95% CI: 2.573, 3.900, P&lt;0.001). Other significant factors associated with higher concomitant statin use include: male gender (OR= 1.296, 95%: 1.079, 1.558, P=0.006), presence of diabetes mellitus (OR=1.262, 95% CI: 1.035, 1.539, P=0.021) and higher Charlson comorbidity score (OR=1.114, 95% CI: 1.046, 1.187, P&lt;0.001) CONCLUSIONS: In this claims data analysis, statins were administered along with ezetimibe more frequently than administered with colesevelam, which should be taken into account when evaluating effectiveness of ezetimibe vs. colesevelam in the real-world treatment of hypercholesterolemia.

Clopidogrel and the possibility of drug–drug interaction in primary health care

IntroductionClopidogrel ineffectiveness is a serious problem in antiplatelet therapy. Many factors may contribute to this phenomenon. One of them is clopidogrel drug–drug interaction with CYP2C19 and CYP3A4 enzyme inhibitors. The main goal of this descriptive study was to assess the prevalence of cases of clopidogrel–drug interactions in the primary health care physicians' practices. Materials and methodsDuring 2010–2011, 80 patients receiving clopidogrel antiplatelet therapy from primary care physicians' clinical practices were involved in this study. By using questionnaires and case histories, the following information was collected: Age, gender, clinical diagnoses, and medications used. ResultsIn the current study, drugs were used that could potentially influence the effect of clopidogrel: Omeprazole, lipophilic statins, calcium channel blockers (CCB). There was a different use of the above-mentioned drugs before and after the initiation of the clopidogrel therapy, e.g., 12 (15.0%) and 44 (55.0%) patients used proton pump inhibitors (PPI) before and after the clopidogrel therapy accordingly (P = 0.16; χ2 = 1.91). However, pantoprazole was recommended more often than other PPI. The use of the potential CYP3A4 inhibitors – lipophilic statins and CCB – was increased after the prescription of clopidogrel too. Concomitant use of statins (mainly atorvastatin) with clopidogrel was observed in 75 (93.8%) patients and the use of CCB (mainly amlodipine) – in 33 (41.3%) patients. ConclusionIn the primary health care practices, it is revealed that there is co-medication of clopidogrel with weak CYP3A4 inhibitors, such as lipophilic statins and amlodipine, and with the moderate CYP2C19 inhibitor – omeprazole. The latter co-medication is potentially harmful and it is very important to inform the first care professionals about the opportunity to change omeprazole to pantoprazole, which does not influence clopidogrel biotransformation.

Concomitant use of clopidogrel and statins and risk of major adverse cardiovascular events following coronary stent implantation

• The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel. • No studies have measured drug exposure in a time-varying manner that detects discontinuation and restart of clopidogrel and statin therapy, allowing clinical quantification of the interaction effect. • Clopidogrel and CYP3A4-metabolizing statin use were each associated with a substantially reduced rate of major adverse cardiovascular events within 12 months after coronary stent implantation. • Although we observed an interaction between use of clopidogrel and statins, statin use vs. non-use was not associated with an increased rate of major adverse cardiovascular events in patients using clopidogrel after coronary stent implantation. To examine whether CYP3A4-metabolizing statin use modified the association between clopidogrel use and major adverse cardiovascular events (MACE) after coronary stent implantation, using time-varying drug exposure ascertainment. We conducted this population-based cohort study in Western Denmark (population: 3 million) using medical databases. We identified all 13 001 patients with coronary stent implantation between 2002 and 2005 and their comorbidities. During 12 months of follow-up, we tracked the use of clopidogrel and CYP3A4-metabolizing statins and the rate of MACE. We used Cox regression to compute hazard ratios (HRs) controlling for potential confounders. The rate of MACE per 1000 person years was 104 for concomitant clopidogrel and statin use, 130 for clopidogrel without statin use, 108 for statin without clopidogrel use and 446 for no use of either drug. The adjusted HR comparing clopidogrel use with non-use was 0.68 (95% confidence interval (CI) 0.58, 0.79) among statin users and 0.34 (95% CI 0.29, 0.40) among statin non-users, yielding an interaction effect (i.e. relative rate increase) of 1.97 (95% CI 1.59, 2.44). The adjusted HR for MACE comparing statin use with non-use was 0.97 (95% CI 0.83, 1.13) among clopidogrel users and 0.49 (95% CI 0.42, 0.57) among clopidogrel non-users. Clopidogrel and CYP3A4-metabolizing statin use were each associated with a substantially reduced rate of MACE within 12 months after coronary stent implantation. Although we observed an interaction between use of clopidogrel and statins, statin use vs. non-use was not associated with an increased rate of MACE in patients using clopidogrel after coronary stent implantation.

Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

Effect of Obesity on Repeat Revascularization in Patients Undergoing Percutaneous Coronary Intervention With Drug‐Eluting Stents

Obesity is a major risk factor for developing coronary artery disease. The impact of obesity on prognosis among those with established coronary disease is less clear. The objective of this study was to evaluate the effect of obesity on repeat revascularization in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). We examined 6,083 patients who were divided into three groups according to BMI: normal (BMI 18.5-24.9 kg/m(2), n = 1,592); overweight (BMI 25-29.9 kg/m(2), n = 3,026) and obese (BMI >30 kg/m(2), n = 1,465). The follow-up focused on clinical-driven repeat revascularization, including target lesion revascularization (TLR) and nonTLR. Median follow-up was 26 months (interquartile range 20-32). There was no significant difference in the incidence of TLR among normal, overweight, and obese patients (6.3% vs. 6.1% vs. 7.1%; P = 0.423). In contrast, the incidence of nonTLR was significantly higher in obese patients compared with normal and overweight (8.4% vs. 6.0% vs. 5.8%, P = 0.003). Multivariate analysis showed that obesity was an independent predictor of nonTLR during follow-up (hazard ratio = 1.39; 95% confidence interval = 1.06-1.83; P = 0.019), along with diabetes and hypercholesterolemia. Concomitant use of statins was independently associated with decreased risk of nonTLR (hazard ratio = 0.75; 95% confidence interval = 0.62-0.92; P = 0.005). In conclusion, among patients undergoing PCI with DES, obesity was not associated with TLR, but was associated with a higher risk of nonTLR.