High Risk Of Vascular Disease Research Articles

Elevated Circulating S100A12 Associates with Vascular Disease and Worse Clinical Outcome in Peritoneal Dialysis Patients.

♦ The pro-inflammatory receptor of advanced glycation end-products (RAGE)-ligand S100A12 is thought to promote, whereas anti-inflammatory soluble RAGE (sRAGE) may protect against, vascular disease. We evaluated circulating S100A12 and sRAGE in relation to vascular disease, inflammation, nutritional status, and mortality risk in peritoneal dialysis (PD) patients. ♦ Plasma S100A12 and sRAGE, biomarkers of inflammation, nutritional status, and comorbidities were analyzed in 82 prevalent PD patients (median age 65 years; 70% men; median vintage 12 months) and, for comparative analysis, also in 190 hemodialysis (HD) patients and 50 control subjects. Associations between mortality risk and concentrations of S100A12 and sRAGE were assessed in PD and HD patients after a mean follow-up period of 31 and 29 months respectively using a competing risk Cox regression model. ♦ In PD patients, median S100A12, sRAGE and S100A12/sRAGE were markedly higher than in controls, and S100A12 was 1.9 times higher and median sRAGE 14% lower compared with HD patients. In PD patients, S100A12 associated with C-reactive protein (ρ = 0.46; p < 0.001) and interleukin-6 (ρ = 0.38; p < 0.001), and, negatively, with s-albumin (ρ = -0.27; p < 0.05) whereas sRAGE associated negatively with body mass index (ρ = -0.37; p < 0.001), fat body mass index (ρ = -0.34; p < 0.001), and lean body mass index (ρ = -0.36; p < 0.001). Peripheral vascular disease or cerebrovascular disease (PCVD) was present in 28% of PD patients and, in multivariate analysis, associated mainly with high S100A12 (odds ratio [OR] 3.52, p = 0.04). In both PD and HD patients, the highest versus other tertiles of S100A12 associated with increased mortality. In contrast, sRAGE did not associate with PCVD or mortality in PD and HD patients. ♦ Plasma S100A12 and sRAGE are markedly elevated in PD patients. Soluble RAGE was inversely related to body mass indices while S100A12 associated with increased inflammation, PCVD, and mortality, suggesting that S100A12 may identify PD patients at high risk for vascular disease and increased mortality.

Systemic Safety of Prolonged Monthly Anti-Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema: A Systematic Review and Meta-analysis.

Anti-vascular endothelial growth factor (VEGF) therapy is commonly used to treat numerous retinal conditions and appears safe, yet controversy remains regarding systemic safety. To evaluate the systemic safety of intravitreous anti-VEGF injections in high-risk patients with diabetic macular edema (DME) and to investigate separately the subgroup of these patients with the highest level of exposure to anti-VEGF monthly treatment for 2 years. A search of MEDLINE, Cochrane Central Register of Controlled Trials, clincaltrials.gov, and ophthalmology congress abstracts January 1, 1947, to May 19, 2015. Randomized clinical trials were selected that evaluated monthly anti-VEGF injections for DME for 2 years and reported the outcome measures of cerebrovascular accidents, myocardial infarctions, arteriothrombotic events, and mortality. Two reviewers collected data independently from each study for the meta-analysis. Data were pooled using a fixed-effects model and analyzed from November 6, 2014, to June 28, 2015. Peto odds ratios with 95% CIs were calculated. Primary end points included cerebrovascular accidents and all-cause mortality in the highest-dose arms. Secondary outcomes included myocardial infarctions, arteriothrombotic events, and vascular-related death. Of 1126 articles reviewed, 598 were removed as duplicate studies and 524, for lack of monthly treatment data for 2 years, leaving 4 studies for the meta-analysis that met the search criteria: 2 trials using monthly aflibercept and 2 using monthly ranibizumab, representing 1328 patients. The primary evaluation (1078 patients) combined the monthly aflibercept and the 0.5-mg ranibizumab arms and yielded an increased risk for death compared with sham and laser treatments (odds ratio [OR], 2.98; 95% CI, 1.44-6.14; P = .003). Analysis including monthly aflibercept and 0.5-mg ranibizumab yielded an increased risk for cerebrovascular accidents (OR, 2.33; 95% CI, 1.04-5.22; P = .04) and vascular death (OR, 2.51; 95% CI, 1.08-5.82; P = .03). No definitive increased risk for myocardial infarctions and arteriothrombotic events was seen with all dose combinations. In this meta-analysis of anti-VEGF agents for patients with DME, assessment of the highest-level exposure group (those high-risk patients with DME who received 2 years of monthly treatment) revealed a possible increased risk for death and potentially for cerebrovascular accidents. Consideration of total exposure to anti-VEGF agents when treating those at high risk for vascular disease may be important.

Evacetrapib: invitro and clinical disposition, metabolism, excretion, and assessment of drug interaction potential with strong CYP3A and CYP2C8 inhibitors.

Evacetrapib is an investigational cholesteryl ester transfer protein inhibitor (CETPi) for reduction of risk of major adverse cardiovascular events in patients with high-risk vascular disease. Understanding evacetrapib disposition, metabolism, and the potential for drug–drug interactions (DDI) may help guide prescribing recommendations. In vitro, evacetrapib metabolism was investigated with a panel of human recombinant cytochromes P450 (CYP). The disposition, metabolism, and excretion of evacetrapib following a single 100-mg oral dose of 14C-evacetrapib were determined in healthy subjects, and the pharmacokinetics of evacetrapib were evaluated in the presence of strong CYP3A or CYP2C8 inhibitors. In vitro, CYP3A was responsible for about 90% of evacetrapib's CYP-associated clearance, while CYP2C8 accounted for about 10%. In the clinical disposition study, only evacetrapib and two minor metabolites circulated in plasma. Evacetrapib metabolism was extensive. A mean of 93.1% and 2.30% of the dose was excreted in feces and urine, respectively. In clinical DDI studies, the ratios of geometric least squares means for evacetrapib with/without the CYP3A inhibitor ketoconazole were 2.37 for area under the curve (AUC)(0–∞) and 1.94 for Cmax. There was no significant difference in evacetrapib AUC(0–τ) or Cmax with/without the CYP2C8 inhibitor gemfibrozil, with ratios of 0.996 and 1.02, respectively. Although in vitro results indicated that both CYP3A and CYP2C8 metabolized evacetrapib, clinical studies confirmed that evacetrapib is primarily metabolized by CYP3A. However, given the modest increase in evacetrapib exposure and robust clinical safety profile to date, there is a low likelihood of clinically relevant DDI with concomitant use of strong CYP3A or CYP2C8 inhibitors.

Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial

Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease. ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years. ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease.

Comprehensive Care for People With Diabetic Kidney Disease.

IN BRIEF Diabetic kidney disease carries a heavy burden, both economically and in terms of quality of life, largely because of its very high risk for vascular disease. Coordinated, multidisciplinary care with attention to appropriate, timely screening and preventive management is crucial to reducing the morbidity and mortality of this devastating disease.

Yiqi Huaju formula, a Chinese herbal medicine, reduces arterial pressure in salt‑sensitive hypertension by inhibiting renin‑angiotensin system activation.

Hypertension is a chronic disease with a high prevalence, and is associated with a high risk of vascular disease and premature death. Traditional Chinese medicine has been administered to treat hypertension for many years. In the present study, the effects of Yiqi Huaju formula (YQ; a compound used in traditional Chinese herbal medicine) were observed in salt‑sensitive hypertension, which was induced by a high‑salt and high‑fat (HSF) diet and the potential mechanism was investigated. YQ was prepared from five plant extracts and was dissolved in normal sodium chloride prior to use. Male Sprague‑Dawley rats were randomly divided into three groups, and fed either a normal diet (control), an HSF diet or an HSF diet with YQ. At week eight, blood pressure was measured and 24‑h urine samples were collected from all of the rats. The rats were subsequently sacrificed, and their blood was collected for biochemical analyses and kidney tissue samples were dissected for the immunohistochemical assay. YQ was observed to decrease the high arterial pressure and serum total cholesterol level, which had been induced by the HSF diet. It also enhanced the excretion of urinary angiotensinogen, Na+, and decreased the loss of urinary aldosterone, K+ and microalbuminuria. In addition, YQ inhibited the high mRNA expression level of renal renin, angiotensin II (Ang II), and Ang II receptor, type 1 (AT1R), and inhibited the protein expression of renal AT1R and Ang II receptor type 2, which had been induced by the HSF diet. These results indicate that YQ may reduce the arterial pressure in salt‑sensitive hypertension via the inhibition of renin‑angiotensin system activation.

Emerging antiplatelet and lipid lowering therapies

Antiplatelet therapy is used widely with proven benefit for the primary prevention of cardiovascular disease as well as for the prevention of further ischemic cardiovascular events in patients with proven coronary artery disease (CAD) and in those with a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternative molecules that may be effective in further reducing the occurrence of events without increasing the risk of bleeding. The armamentarium of antiplatelet therapy has been further enriched by ticagrelor, cangrelor, vorapaxar, prasugrel and atopaxar. Ticagrelor was approved in 2011 by the European Medicines Agency swiftly followed by the US Food and Drug Administration. Reversible antiplatelet agents acting as P2Y12 antagonists similar to ticagrelor are cangrelor, and elinogrel. A new class of oral protease-activated receptor-1 (PAR-1) inhibitors, vorapaxar and atopaxar has also been proposed as effective antiplatelets but their clinical benefit is still under debate. The P2Y12 antagonists prasugrel and ticagrelor prevent adverse cardiac outcomes albeit their absolute benefit is very small. The beneficial effect of prasugrel and ticagrelor comes at a cost of an increased risk of bleeding. Furthermore, new adverse effects have also become evident with the new P2Y12 antagonists and these include dyspnea (for all of the reversible P2Y12 antagonists: ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y12 antagonists have a peculiar pharmacodynamic profile with a fast onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients who undergo coronary artery bypass graft (CABG) surgery. Trials with the PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. Physicians must carefully assess patient-specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk. In addition to adequate anti-platelet therapy the treatment of blood lipids is important for the primary and secondary prevention of cardiovascular disease. Elevated low-density lipoprotein cholesterol is an important risk factor for cardiovascular and cerebrovascular events. HMG-CoA reductase inhibitors, or statins, are very effective in lowering cholesterol levels, and in reducing mortality and cardiovascular events in patients with and without cardiovascular disease. The evidence cumulated with the studies conducted with statin has led to the recent recommendations that all patients with known vascular disease, or who are at high risk for vascular disease, should be considered candidates for statin therapy. Nonstatin therapies (either as monotherapy or in addition to statins) to reduce LDL cholesterol by mechanisms that do not involve inhibition of HMG-CoA reductase are likely to be useful for patients in need of LDL reduction; particularly those who either cannot take statins or respond only partially or not at all to statins alone. These therapies include cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase inhibitors, farnesoid X receptor antagonists, sterolregulating binding protein cleavage activating protein, and microsomal triglyceride transfer protein. Recent studies with the PCSK9 have shown that these drugs significantly reduce total and LDL cholesterol in patients with familial hypercholesterolaemia and that are effective in further reducing plasma cholesterol levels in patients receiving statins. Therefore, therapeutic options are becoming available for patients who cannot tolerate full dose statin therapy or for those few patients who are intolerant to statin therapy.

Clinical Implications

HomeHypertensionVol. 65, No. 4Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Apr 2015https://doi.org/10.1161/HYPERTENSIONAHA.115.05374Hypertension. 2015;65:697Renal Denervation and Atherosclerosis (page 758)Sympathetic nervous system overactivity is associated with a variety of cardiovascular diseases. Sympathetic innervation to specific organs may be particularly relevant. For example, renal sympathetic activity may play an important role in hypertension by regulating renin–angiotensin–aldosterone system activity, as well as other humoral factors. These downstream factors may also affect other vascular disease processes, such as atherosclerosis, independent of hypertension. In this issue of Hypertension, Wang et al report the effects of renal denervation (RDN) in a normotensive, atherosclerosis-prone mouse model. Despite absence of effects on blood pressure or total cholesterol, mice receiving bilateral RDN developed less atherosclerosis compared with mice receiving a sham operation (Figure). Atherosclerotic lesions in RDN mice also appeared more stable with increased smooth muscle cell content. Protection from atherosclerosis in the RDN group was associated with reduction of systemic factors implicated in the progression of atherosclerosis, including aldosterone, monocyte chemoattractant protein-1, and a marker of oxidative stress, 8-isoprostane. Further studies will be necessary to identify the precise causal mechanism(s) responsible for the apparent beneficial effects of RDN on progression of atherosclerosis, so that this pathway might be targeted in subjects at high risk for vascular disease. Complications of atherosclerosis (or surrogate end points) should also be studied if future clinical RDN trials in humans are performed.Download figureDownload PowerPointPreeclampsia Potentiates Future Vascular Injury (page 863)Download figureDownload PowerPointWomen who develop preeclampsia during pregnancy have an increased risk of cardiovascular disease later in life. Preeclampsia affects 5% of pregnancies, thereby exposing many women to increased cardiovascular risk for which there is no treatment aside from modification of traditional risk factors. The pervading explanation for this 2- to 4-fold increased cardiovascular risk is that preeclampsia identifies woman destined to develop cardiovascular disease. This is based on data revealing common risk factors for preeclampsia and cardiovascular disease. In this issue of Hypertension, Pruthi et al provide data supporting a novel emerging theory in which permanent vascular damage sustained during the preeclamptic episode contributes directly to cardiovascular disease pathogenesis. They demonstrate for the first time that mice exposed to experimental preeclampsia retain an enhanced response to vascular injury months after preeclampsia resolves. In their study, mice without preexisting cardiovascular risk factors were exposed to wire carotid injury 2 months after experimental preeclampsia. Preeclampsia-exposed mice developed increased vessel thickening and enhanced vascular cell proliferation and fibrosis after injury. Exploration of the mechanism for these persistent changes in the vasculature after preeclampsia has the potential to yield totally novel therapies to prevent this vascular damage during preeclampsia or to treat women after preeclampsia to avert the rapid progression to cardiovascular disease.Sofalcone Upregulates Heme Oxygenase-1 and Decreases Soluble fms–Like Tyrosine Kinase 1 (page 855)Preeclampsia complicates 3% to 8% of all pregnancies and is globally responsible for an estimated 60 000 maternal deaths annually and a far greater number of fetal losses. A therapeutic for preeclampsia could be a significant breakthrough, saving mothers and babies. Sadly, there is no such treatment. Solfacone is widely used as an antiulcer agent in Asia. In this issue of Hypertension, Onda et al report studies showing Solfacone has 3 different biological actions that raise the surprising possibility that it may be a treatment for preeclampsia. Preeclampsia is strongly associated with oxidative stress. The team reports Solfacone switches on a master transcription factor (Nrf2) that translocates to the nucleus and upregulates a raft of antioxidant genes. Secondly, the preeclamptic placenta produces elevated levels of soluble fms–like tyrosine kinase 1, which circulates widely, causing maternal endothelial dysfunction. Onda et al found Solfacone decreased soluble fms–like tyrosine kinase 1 secretion. Finally, circulating placental factors (including soluble fms–like tyrosine kinase 1) cause widespread endothelial dysfunction that leads to hypertension and multiple maternal organ injury. The team used several assays to show that Solfacone may protect blood vessels by decreasing endothelial dysfunction (Figure). Although there is little data on the safety of Solfacone in pregnancy, no links have been made with adverse pregnancy outcomes. Therefore, it is justifiable to proceed to clinical trials to treat women having severe preeclampsia with Solfacone where clinical options are limited.Download figureDownload PowerPoint Previous Back to top Next FiguresReferencesRelatedDetails April 2015Vol 65, Issue 4 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.115.05374 Originally publishedApril 1, 2015 PDF download Advertisement

Dose Titration, Persistence, and Adherence to Statin Therapy Among Patients with High-Risk Vascular Disease in Japan.

Dose Titration, Persistence, and Adherence to Statin Therapy Among Patients with High-Risk Vascular Disease in Japan.

Rapid clinical improvement of peripheral artery occlusive disease symptoms after nilotinib discontinuation despite persisting vascular occlusion

Rapid clinical improvement of peripheral artery occlusive disease symptoms after nilotinib discontinuation despite persisting vascular occlusion

Preventing Dementia in Older Cardiovascular Patients

Cardiovascular disease (CVD) contributes to risk of dementia by either enhancing the development and progression of brain vascular disease and subsequent neurodegeneration and Alzheimer's disease (AD) pathology, ie, amyloid plaques and neurofibrillary tangles, acts as a precipitant of dementia in older individuals with preexisting subclinical neuropathology of dementia. Atrial fibrillation, congestive heart failure (CHF), stroke, and myocardial infarction are associated with increased risk of dementia. All older individuals age 65–70+ can be considered to be at very high risk of vascular disease and dementia and candidates for aggressive CV preventive therapies, such as lipid lowering, antihypertensive therapy, increased physical activity, antidiabetic therapies, smoking cessation, etc to prevent heart attacks subsequent CHF, atrial fibrillation, stroke, frailty, and dementia. Furthermore, preventing or delaying dementia should be a primary outcome of all CV trials in older individuals.

PCV52 - Health Care Costs And Resource Utilization In Working Age Patients With High Risk Vascular Disease: Findings From A Multi-Employer Claims Database

PCV52 - Health Care Costs And Resource Utilization In Working Age Patients With High Risk Vascular Disease: Findings From A Multi-Employer Claims Database

PCV53 - Health Care Costs And Resource Utilization In Elderly Patients With High Risk Vascular Disease

PCV53 - Health Care Costs And Resource Utilization In Elderly Patients With High Risk Vascular Disease

PCV115 - Treatment Patterns With Lipid-Altering Drugs In High-Risk Vascular Disease In The United Kingdom

PCV115 - Treatment Patterns With Lipid-Altering Drugs In High-Risk Vascular Disease In The United Kingdom

Long-term efficacy and safety of statin treatment beyond six years: A meta-analysis of randomized controlled trials with extended follow-up

Large-scale randomized controlled trials (RCTs) have well demonstrated the beneficial effects of cholesterol-lowering treatment with statins in patients at high risk of vascular disease. However, large statin RCTs were usually restricted to the typical 5–6 years. Moreover, non-cardiovascular events, especially the risk of cancer, probably failed to emerge within a restricted period of 6 years. The aim of this study was to evaluate the long-term efficacy and safety of statin treatment by performing a meta-analysis of statin RCTs with extended follow-up beyond 6 years. Six RCTs with post-trial follow-up were eligible for inclusion, involving 47,296 patients with total follow-up ranging from 6.7 to 14.7 years. During the post-trial period, all the surviving participants were advised to take a statin and the cholesterol level were almost identical between the original statin group and the original placebo group. Over the entire 6.7–14.7 years of follow-up, a significant reduction in the rates of all-cause mortality (relative risk 0.90, 95% confidence interval 0.85–0.96; P=0.0009), cardiovascular mortality (0.87, 0.81–0.93; P<0.0001) and major coronary events (0.79, 0.72–0.86; P<0.00001) was observed in favour of the original statin group. During 2-year post-trial period, further reduction in all-cause mortality (0.83, 0.74–0.93; P=0.001), cardiovascular mortality (0.81, 0.69–0.95; P=0.01) and major coronary events (0.77, 0.63–0.95; P=0.01) was observed among initially statin-treated patients. Over the entire follow-up period, statin treatment did not increase the incidence of cancers (0.99, 0.95–1.04; P=0.79), deaths from cancers (1.00, 0.93–1.07; P=0.98) and non-cardiovascular mortality (0.95, 0.90–1.00; P=0.07). In conclusion, statin treatment beyond 6 years is effective and safe in patients at high risk of vascular events. Moreover, earlier treatment with statin may not only preserve the initial benefit but also have further survival benefit for additional 2 years. Further studies are called for to explore the underlying mechanisms.

Long‐term risk of recurrent vascular events after young stroke: The FUTURE study

Long-term data on recurrent vascular events after young stroke are limited. Our objective was to examine the long-term risk of recurrent vascular events after young stroke. We prospectively included 724 consecutive patients with a first-ever transient ischemic attack (TIA), ischemic stroke, or intracerebral hemorrhage (ICH), aged 18 to 50 years, admitted to our hospital between January 1, 1980 and November 1, 2010. Outcomes were (1) stroke; (2) myocardial infarction or cardiac or peripheral arterial revascularization procedures; or (3) composite event of these, whichever occurred first. After a mean follow-up of 9.1 years (standard deviation = 8.2, range = 0-31.0), 142 patients (19.6%) had at least 1 recurrent vascular event. Cumulative 20-year risk of stroke was 17.3% (95% confidence interval [CI] = 9.5-25.1) after TIA, 19.4% (95% [CI] = 14.6-24.3) after ischemic stroke, and 9.8% (95% CI = 1.0-18.7) after ICH. Cumulative 20-year risk of any vascular event was 27.7% (95% CI = 18.5-37.0) after TIA and 32.8% (95% CI = 26.7-38.9) after ischemic stroke. Age and male sex were associated with other arterial events, but not with stroke. Among TOAST (Trial of Org 10172 in Acute Stroke Treatment) subtypes, adjusted for age, sex, and decennium of inclusion, atherothrombotic stroke, cardioembolic stroke, and lacunar stroke were associated with recurrent stroke (hazard ratio [HR] = 2.72, 95% CI = 1.34-5.52; HR = 2.49, 95% CI = 1.23-5.07; and HR = 2.92, 95% CI = 1.45-5.88, respectively). Patients with young stroke remain at substantial risk of recurrent vascular events for decades, suggesting that the underlying disease that caused stroke at a young age continues to put these patients at a high risk for vascular disease throughout their lives.

Abstract 77: Statin Adherence and Persistence Among Japanese Patients With High Risk Vascular Disease: A Japan Claims Database Analysis

BACKGROUND: High risk vascular disease (HRVD defined as cerebrovascular disease [CVD], coronary artery disease with diabetes [CADD], history of acute coronary syndrome [ACS], or peripheral artery disease [PAD]) is among the biggest health problems affecting Japanese, with CVD and coronary artery disease (CAD) being the 2nd and 3rd most common causes of death. Despite proven efficacy of statins in reducing CV mortality, limited research is available to systematically study statin adherence and persistence for HRVD patients in Japan. OBJECTIVE: Examine statin adherence and persistence in HRVD patients. METHOD: A retrospective cohort study was conducted using the Japan Medical Data Center (JMDC) database, a large Japanese administrative claims database with 10 insurance societies (payers), and integrated inpatient, outpatient, and pharmacy claims of approximately 0.8 million covered lives from 2006-2011. Patients &gt; 18 years with HRVD (CVD, PAD, CADD or history of ACS [≥30days through 365 days after discharge for ACS]) between 01/01/2008 to 12/31/2009, were identified for this study with minimum 12-month pre- and 24-month post-index insurance eligibility. Statin use was measured during the 12-month baseline period and the 24-month follow-up period. The date of the first HRVD claim(s) satisfying the above inclusion criteria was defined as the index date. Statin use was examined for the overall HRVD group as well as subgroups of patients with CVD only, PAD only, CADD only, history of ACS only, and patients with multiple HRVDs. Statin adherence, calculated using the medication possession ratio [MPR], and statin persistence, assessed with survival analysis techniques using a ≥30-day gap to define discontinuation, were measured in the 24-month follow-up period for the overall HRVD patient group. RESULTS: There were 10,400 HRVD patients identified in the JMDC database. Mean age was 52.8 and 57.1% were male. Statin use during the baseline period showed 12.1% of HRVD patients taking statins (CVD only: 10.2%; PAD only: 9.6%; CADD only: 14.6%; history of ACS only: 46.7%; CADD and a history of ACS: 48.3%; 2 affected artery beds: 17.8%; 3 affected artery beds: 19.5%). Statin use increased to 32.9% during the 24-month follow-up period (CVD only: 27.6%; PAD only: 26.6%; CADD only: 45.1%; history of ACS only: 54.4%; CADD and a history of ACS: 58.3%; 2 affected artery beds: 49.3%; 3 affected artery beds: 45.5%). For Japanese HRVD patients who used a statin, mean/median MPR was 0.89/0.94 and 82.1% of statin users were adherent (MPR ≥80%) to their statin therapy during the 24-month follow up period. The median time to statin discontinuation was 679 days during the 24-month follow up period. CONCLUSION: Statin use after HRVD diagnosis was modest and highest in ACS patients and patients with multiple affected vascular beds. Statin adherence was high among patients with HRVD in Japan.

PCV33 - High-risk vascular disease in japan: evidence on incidence, patient characteristics, and treatment rates from a large Japanese claims database

PCV33 - High-risk vascular disease in japan: evidence on incidence, patient characteristics, and treatment rates from a large Japanese claims database

PCV129 - Demographic and clinical characteristics, and treatment of cardiovascular risk factors in working age patients with high-risk vascular disease: Findings from a multi-employer U.S. claims database

PCV129 - Demographic and clinical characteristics, and treatment of cardiovascular risk factors in working age patients with high-risk vascular disease: Findings from a multi-employer U.S. claims database

PCV141 - Demographic and clinical characteristics, and treatment of cardiovascular risk factors among U.S. elderly patients with high-risk vascular disease

PCV141 - Demographic and clinical characteristics, and treatment of cardiovascular risk factors among U.S. elderly patients with high-risk vascular disease