Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration: isrctn.com Identifier: ISRCTN57819173.

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.

The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study.

AIMS: Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS. METHODS AND RESULTS: A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting <48 h from onset of chest pain. Treatment was 1:1 allocation to daily, subcutaneous IL-1receptor antagonist (IL-1ra) or placebo for 14 days. Baseline characteristics were well matched. Treatment compliance was 85% at 7 days. The primary endpoint (area-under-the-curve for C-reactive protein over the first 7 days) was: IL-1ra group, 21.98 mg day/L (95%CI 16.31-29.64); placebo group, 43.5 mg day/L (31.15-60.75) (geometric mean ratio = 0.51 mg/L; 95%CI 0.32-0.79; P = 0.0028). In the IL-1ra group, 14-day achieved high-sensitive C-reactive protein (P < 0.0001) and IL-6 levels (P = 0.02) were lower than Day 1. Sixteen days after discontinuation of treatment (Day 30) high-sensitive C-reactive protein levels had risen again in the IL-1ra group [IL-1ra; 3.50 mg/L (2.65-4.62): placebo; 2.21 mg/L (1.67-2.92), P = 0.022]. MACE at Day 30 and 3 months was similar but at 1 year there was a significant excess of events in the IL-1ra group. CONCLUSION: IL-1 drives C-reactive protein elevation at the time of NSTE-ACS. Following 14 days IL-1ra treatment inflammatory markers were reduced. These results show the importance of IL-1 as a target in ACS, but also indicate the need for additional studies with anti-IL-1 therapy in ACS to assess duration and safety. CLINICAL TRIAL REGISTRATION EUCTR: 2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB.

Effects of nebivolol on biomarkers in elderly patients with heart failure.

BACKGROUND: Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure. METHODS: In a subset of patients in SENIORS we measured N-terminal pro-brain natriuretic peptide (NT-BNP), pro atrial natriuretic peptide (Pro-ANP), endothelin-1 (ET-1), peripheral norepinephrine (PNE), soluble Fas (sFas), soluble Fas-ligand (sFas-L), tumour necrosis factor-alpha (TNF-α), serum uric acid (SUA), symmetrical dimethyl arginine (SDMA), arginine, citrulline and asymmetrical dimethyl arginine (ADMA) at baseline (before study drug), at 6 months and 12 months in a prespecified substudy. RESULTS: One hundred and six patients were enrolled and 75 had a baseline and at least one follow-up sample. There were no significant differences in neurohormone cytokines or nitric oxide markers measured between the two groups at six or twelve months. NT-ProBNP showed a numerical increase in the nebivolol group compared to placebo (P=0.08) and sFas showed a numerical increase in patients on placebo (P=0.08). Mean baseline LVEF was 35% in both groups and at 12 months was 43% on nebivolol group and 34% on placebo group (P=0.01). CONCLUSION: There were trends but no clear changes associated with nebivolol in neurohormones, cytokines or markers of nitric oxide activity in this study of elderly patients with heart failure. Further studies are needed to understand the mechanistic effects of beta blockers on biomarkers in heart failure.

Comparison of drug-eluting and bare-metal stents in patients with diabetes undergoing primary percutaneous coronary intervention: what is the evidence?

A best evidence topic was written according to a structured protocol. The question addressed was, should the practising interventional cardiologist use drug-eluting stents (DESs) or bare-metal stents (BMSs) when undertaking primary percutaneous coronary intervention (PCI) in diabetic patients. The relevant outcomes that were used to determine the answer to this question included: in-stent restenosis, target vessel revascularization (TVR), mortality, myocardial infarction and in-stent thrombosis. The OVID Medline database was used to carry out the reported search for abstracts of relevant journal articles. Altogether 102 papers were found, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. From the evidence available, we conclude that in-stent restenosis is less likely to occur over a follow-up of at least 6 months if a DES is used instead of a BMS. Furthermore, TVR is less likely to be required in diabetic patients who receive a DES in comparison with a BMS. Nevertheless, no significant difference in mortality between stents was detected by the studies reviewed. This included no difference in the incidence of cardiac and non-cardiac causes of death. There was evidence showing that DESs are associated with a decrease in the risk of myocardial infarction and, in particular, a decrease in non-Q-wave myocardial infarction. However, there was also conflicting evidence demonstrating no significant difference in the incidence of myocardial infarction between diabetic patients who had received a BMS or a DES. Moreover, the available evidence showed no significant difference in the risk of in-stent thrombosis for all DESs with the exception of Sirolimus eluting stents in which the evidence was not consistent. In summary, the available evidence supports the use of DESs over BMSs in diabetic patients undergoing primary PCI.

Role of multidetector computed tomography in the diagnosis and management of patients attending the rapid access chest pain clinic, The Scottish computed tomography of the heart (SCOT-HEART) trial: study protocol for randomized controlled trial.

BACKGROUND: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic. METHODS/DESIGN: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014. DISCUSSION: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01149590.

Atopaxar and its effects on markers of platelet activation and inflammation: results from the LANCELOT CAD program.

Atopaxar is a reversible protease activated receptor (PAR)-1 thrombin receptor antagonist that interferes with platelet signaling. The effects of PAR-1 antagonists on biomarkers remain unknown. The primary objective was to assess the effects of atopaxar on biomarkers of inflammation and platelet activation. The LANCELOT-CAD trial randomized 720 subjects to atopaxar (50, 100, or 200 mg daily) or matching placebo for 24 weeks. Biomarkers were assessed at serial time points. A linear mixed model to account for repeated measures was used to evaluate the change in biomarker concentration from randomization across time to week 24. Least square means were determined from the linear mixed models. The concentration of sCD40L decreased on average over time by -553 (95 % CI -677, -429) ng/L in the combined atopaxar group versus -30.3 (-249 to 189) ng/L fall in the placebo arm (P < 0.001) and a dose-dependent trend was seen across treatment groups (P < 0.001 for trend). In contrast, Lp-PLA(2) mass rose on average over time by 12.6 (95 % CI 10.0, 15.3) ng/ml in the combined atopaxar group as compared with 2.6 (95 % CI -2.1, 7.3) ng/ml in the placebo arm (P < 0.001). Similarly, the concentration of IL-18 rose by 17.5 (95 % CI 12.4, 22.6) pg/ml in the atopaxar group versus a -1.2 (95 % CI -10.2, 7.8) pg/ml fall in the placebo group (P < 0.001). The effects of atopaxar on Lp-PLA(2) and IL-18 appeared to be dose-dependent (P < 0.001 for trend) and were observed in J-LANCELOT. Atopaxar did not have a significant effect on other inflammatory markers. In conclusion, atopaxar appeared to decrease sCD40L, but did not demonstrate an anti-inflammatory effect in patients with stable CAD. Although atopaxar increased the concentration of Lp-PLA(2) and IL-18, the clinical relevance of these findings remains unknown and warrants further investigation and validation.

Prevalence and outcome of subclinical rheumatic heart disease in India: the RHEUMATIC (Rheumatic Heart Echo Utilisation and Monitoring Actuarial Trends in Indian Children) study.

OBJECTIVE: To study the prevalence and medium term outcome of subclinical rheumatic heart disease (RHD) in India. DESIGN: Cross sectional echocardiographic screening study. SETTING: School children aged 5-15 years living in rural areas of north India. PATIENTS: A cross sectional echocardiographic screening study was carried out among 6270 randomly selected school children aged 5-15 years (10.8 ± 2.6 years; 52.7% male). Of all the abnormal cases, 100 children (78%) were restudied at a mean follow-up of 15.4 ± 6.6 months. INTERVENTION: Echocardiographic screening. MAIN OUTCOME MEASURE: Echocardiography-Doppler criteria based prevalence of RHD. RESULTS: Clinical examination detected mitral regurgitation in five patients and the estimated prevalence of clinical RHD was 0.8/1000 school children. Echocardiography-Doppler diagnosed RHD in 128 cases, giving a prevalence of 20.4/1000 school children (95% CI 16.9 to 23.9/1000 children). On multivariate analysis, older age (OR 1.93, 95% CI 1.29 to 2.88; p = 0.001), female sex (OR 1.84, 95% CI 1.25 to 2.72; p = 0.002) and government funded school student, which is a surrogate measure of lower socioeconomic status (OR 1.55, 95% CI 1.02 to 2.34; p = 0.039) were found to be independent predictors of RHD. On follow up, the severity of subclinical RHD was non-progressive in 68 children (68%) while it worsened in four (4%) and regressed in 28 children (28%). CONCLUSIONS: The prevalence of RHD is several fold higher using echocardiographic screening compared with clinical examination. The prevalence is higher among girls and children of lower socioeconomic status. In the majority of cases, subclinical RHD appears to be non-progressive on medium term follow up. Routine echocardiographic screening may be indicated in populations at high risk of RHD.

Assessment of data quality in an international multi-centre randomised trial of coronary artery surgery.

BACKGROUND: ART is a multi-centre randomised trial of cardiac surgery which provided a unique opportunity to evaluate the data from a large number of centres from a variety of countries. We attempted to assess data quality, including recruitment rates, timeliness and completeness of the data obtained from the centres in different socio-economic strata. METHODS: The analysis was based on the 2-page CRF completed at the 6 week follow-up. CRF pages were categorised into "clean" (no edit query) and "dirty" (any incomplete, inconsistent or illegible data). The timelines were assessed on the basis of the time interval from the visit and receipt of complete CRF. Data quality was defined as the number of data queries (in percent) and time delay (in days) between visit and receipt of correct data. Analyses were stratified according to the World Bank definitions into: "Developing" countries (Poland, Brazil and India) and "Developed" (Italy, UK, Austria and Australia). RESULTS: There were 18 centres in the "Developed" and 10 centres in the "Developing" countries. The rate of enrolment did not differ significantly by economic level ("Developing":4.1 persons/month, "Developed":3.7 persons/month). The time interval for the receipt of data was longer for "Developing" countries (median:37 days) compared to "Developed" ones (median:11 days) (p < 0.001). The median number of data queries was 23% in "Developed" countries compared to 19% in "Developing" ones (p = ns). CONCLUSIONS: In this study we showed that data quality was comparable between centres from "Developed" and "Developing" countries. Data was received in a less timely fashion from Developing countries and appropriate systems should be instigated to minimize any delays. Close attention should be paid to the training of centres and to the central management of data quality. TRIAL REGISTRATION: ISRCTN46552265.

What goes into a major acute coronary syndrome trial and what will future trials look like?

Acute coronary syndromes (ACS) are common and carry a high risk of death and serious complications. Over the past three decades, the international cardiology community has collaborated in numerous large, well-designed randomized trials evaluating promising new treatments leading to important improvements in care for patients with ACS. Industry has funded most of the ACS trials of new pharmacologic treatments, but there are many independently funded trials evaluating treatment strategies such as percutaneous coronary intervention. Improvements in ACS care have led to challenges in demonstrating the efficacy of new treatments and many current trials are comparing one active treatment against another, although new paradigms including anti-inflammatory treatments and stem cell infusions are being tested against placebo. Developing new drugs for ACS is a very expensive process with many trials not showing any benefit, and much of this expense is related to the cost of large multicenter phase 3 trials. Reducing the administrative burden and associated costs of ACS trials is an important immediate goal if the strong tradition of large collaborative trials is to continue, as well as the need for health care providers to engage more actively in the clinical research process and support large multinational independently funded trials. We discuss methodologic issues of ACS trials with recent examples and provide some perspectives for the future.

Hepatic metabolism and transporter gene variants enhance response to rosuvastatin in patients with acute myocardial infarction: the GEOSTAT-1 Study.

BACKGROUND: Pharmacogenetics aims to maximize benefits and minimize risks of drug treatment. Our objectives were to examine the influence of common variants of hepatic metabolism and transporter genes on the lipid-lowering response to statin therapy. METHODS AND RESULTS: The Genetic Effects On STATins (GEOSTAT-1) Study was a genetic substudy of Secondary Prevention of Acute Coronary Events-Reduction of Cholesterol to Key European Targets (SPACE ROCKET) (a randomized, controlled trial comparing 40 mg of simvastatin and 10 mg of rosuvastatin) that recruited 601 patients after myocardial infarction. We genotyped the following functional single nucleotide polymorphisms in the genes coding for the cytochrome P450 (CYP) metabolic enzymes, CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C), CYP2C19*2 (681G>A), CYP3A5*1 (6986A>G), and hepatic influx and efflux transporters SLCO1B1 (521T>C) and breast cancer resistance protein (BCRP; 421C>A). We assessed 3-month LDL cholesterol levels and the proportion of patients reaching the current LDL cholesterol target of <70 mg/dL (<1.81 mmol/L). An enhanced response to rosuvastatin was seen for patients with variant genotypes of either CYP3A5 (P=0.006) or BCRP (P=0.010). Furthermore, multivariate logistic-regression analysis revealed that patients with at least 1 variant CYP3A5 and/or BCRP allele (n=186) were more likely to achieve the LDL cholesterol target (odds ratio: 2.289; 95% CI: 1.157, 4.527; P=0.017; rosuvastatin 54.0% to target vs simvastatin 33.7%). There were no differences for patients with variants of CYP2C9, CYP2C19, or SLCO1B1 in comparison with their respective wild types, nor were differential effects on statin response seen for patients with the most common genotypes for CYP3A5 and BCRP (n=415; odds ratio: 1.207; 95% CI: 0.768, 1.899; P=0.415). CONCLUSION: The LDL cholesterol target was achieved more frequently for the 1 in 3 patients with CYP3A5 and/or BCRP variant genotypes when prescribed rosuvastatin 10 mg, compared with simvastatin 40 mg. Clinical Trial Registration- URL: http://isrctn.org. Unique identifier: ISRCTN 89508434.

Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study.

AIMS: The PREDICT Study is a prospective cohort study designed to evaluate coronary artery calcification score (CACS) as a predictor of cardiovascular events in type 2 diabetes (T2DM). METHODS AND RESULTS: A total of 589 patients with no history of cardiovascular disease and with established T2DM had CACS measured, as well as risk factors, including plasma lipoprotein, apolipoprotein, homocysteine and C-reactive protein concentrations, homeostasis model assessment insulin resistance (HOMA-IR), and urine albumin creatinine ratio. Participants were followed for a median of 4 years and first coronary heart disease (CHD) and stroke events were identified as primary endpoints. There were 66 first cardiovascular events (including 10 strokes). CACS was a highly significant, independent predictor of events (P < 0.001), with a doubling in CACS being associated with a 32% increase in risk of events (29% after adjustment). Hazard ratios relative to CACS in the range 0-10 Agatston units (AU) were: CACS 11-100 AU, 5.4 (P = 0.02); 101-400 AU 10.5 (P = 0.001); 401-1000 AU, 11.9 (P = 0.001), and >1000 AU, 19.8 (P < 0.001). Only HOMA-IR predicted primary endpoints independently of CACS (P = 0.01). The areas under the receiver operator characteristic curve for United Kingdom Prospective Diabetes Study (UKPDS) risk engine primary endpoint risk and for UKPDS risk plus CACS were 0.63 and 0.73, respectively (P = 0.03). CONCLUSION: Measurement of CACS is a powerful predictor of cardiovascular events in asymptomatic patients with T2DM and can further enhance prediction provided by established risk models.

The progress of coronary heart disease in Type 2 diabetes as measured by coronary calcium score from electron beam computed tomography (EBCT): the PREDICT study.

Coronary calcification score (CACS) measured by electron beam tomography is well established in the evaluation of cardiovascular risk in general populations. The PREDICT study aims to evaluate prediction of cardiovascular events by CACS in Type 2 diabetic subjects without previous clinical cardiovascular disease. In the present PREDICT sub-study, the rate of progression of CACS and factors influencing this rate were assessed. CACS was measured at baseline and after a mean interval of 4.0 (range of 2.1-5.0) years in the 202 PREDICT participants who agreed to have a second scan. Participants also had a range of conventional and novel biochemical risk factors measured at baseline. Progression of calcification was apparent in 170 (84%), while in 32 (16%) there was regression or no progression. Those showing progression had a significantly more adverse risk factor profile. Rate of change in CACS was strongly related to baseline CACS (p<0.0001). Rate of change also correlated with, waist:hip ratio (p=0.004), male gender (p=0.009), age (p=0.04), use of antihypertensive drugs (p=0.03) and statins (p=0.05) and, independently of baseline CACS, systolic blood pressure (p=0.0006), waist circumference (p=0.001) and urine albumin:creatine ratio (p=0.04). Most subjects with Type 2 diabetes showed progression of CACS. The absence of a relationship between progression and lipid risk factors and the positive relationship with statin and antihypertensive drug use may reflect earlier risk factor exposure. Independent relationships between progression and established calcification, blood pressure, central adiposity and urine albumin:creatinine ratio suggest areas for risk factor modification that could be especially relevant in Type 2 diabetes.

A global view of atherothrombosis: baseline characteristics in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial.

BACKGROUND: The manifestations of atherothrombosis such as myocardial infarction, ischemic stroke, limb ischemia, or cardiovascular death pose a global health care burden. Additional therapies to decrease ischemic events in patients with established vascular disease or at risk for developing vascular disease are necessary. We sought to characterize the risk factors and treatments of a diverse contemporary population of patients with atherothrombosis. METHODS: The CHARISMA trial has enrolled 15,603 patients from around the world. Patients with established coronary, cerebrovascular, or peripheral arterial disease, or those at high risk of developing atherothrombosis due to multiple risk factors, have been randomized to receive either the adenosine diphosphate receptor antagonist clopidogrel or placebo, in addition to background therapy with low- to moderate-dose aspirin. RESULTS: A high percentage of enrolled patients are being treated with statins and angiotensin-converting enzyme inhibitors. In the CHARISMA population, a total of 75.6% of the population had an abnormal body mass index: 42.2% were overweight and 33.4% were obese, with particularly high rates in the United States, especially of morbid obesity. Correspondingly, the prevalence of diabetes was 42%. CONCLUSION: The CHARISMA trial will further characterize atherothrombosis and provide insight into the role of dual antiplatelet therapy in improving outcomes in patients with multiple risk factors or established vascular disease. Of note, the rates of obesity and diabetes in patients with atherothrombosis throughout the world are particularly alarming.

One-year outcomes of coronary artery bypass graft surgery versus percutaneous coronary intervention with multiple stenting for multisystem disease: a meta-analysis of individual patient data from randomized clinical trials.

BACKGROUND: We aimed to provide a quantitative analysis of the 1-year clinical outcomes of patients with multisystem coronary artery disease who were included in recent randomized trials of percutaneous coronary intervention with multiple stenting versus coronary artery bypass graft surgery. METHODS: An individual patient database was composed of 4 trials (Arterial Revascularization Therapies Study, Stent or Surgery Trial, Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Multivessel Disease 2, and Medicine, Angioplasty, or Surgery Study 2) that compared percutaneous coronary intervention with multiple stenting (N = 1518) versus coronary artery bypass graft surgery (N = 1533). The primary clinical end point of this study was the combined incidence of death, myocardial infarction, and stroke at 1 year after randomization. Secondary combined end points included the incidence of repeat revascularization at 1 year. All analyses were based on the intention-to-treat principle. RESULTS: After 1 year of follow-up, 8.7% of patients randomized to percutaneous coronary intervention with multiple stenting versus 9.1% of patients randomized to coronary artery bypass graft surgery reached the primary clinical end point (hazard ratio 0.95 and 95% confidence interval 0.74-1.2). Repeat revascularization procedures occurred more frequently in patients allocated to percutaneous coronary intervention with multiple stenting compared with coronary artery bypass graft surgery (18% vs 4.4%; hazard ratio 4.4 and 95% confidence interval 3.3-5.9). The percentage of patients who were free from angina was slightly lower after percutaneous coronary intervention with multiple stenting than after coronary artery bypass graft surgery (77% vs 82%; P = .002). CONCLUSIONS: One year after the initial procedure, percutaneous coronary intervention with multiple stenting and coronary artery bypass graft surgery provided a similar degree of protection against death, myocardial infarction, or stroke for patients with multisystem disease. Repeat revascularization procedures remain high after percutaneous coronary intervention, but the difference with coronary artery bypass graft surgery has narrowed in the era of stenting.

Mortality following non-ST elevation acute coronary syndrome: 4 years follow-up of the PRAIS UK Registry (Prospective Registry of Acute Ischaemic Syndromes in the UK).

AIM: To present information on long-term prognosis and risk factors following an admission with non-ST elevation acute coronary syndrome. METHODS: A cohort of 653 patients was followed for mortality and causes of death using data from the UK Office of National Statistics (ONS). Cox proportional hazards model was used to identify the prognostic factors. RESULTS: Overall survival at a maximum follow-up of 45 months was 77.8% (95% CI 74.1-81.1%). Seventy-three per cent of the deaths were clearly due to a cardiovascular cause. Age, male gender, heart failure, ST depression or bundle branch block were all associated with higher short- and long-term risk. Taking aspirin or having a revascularization procedure, over the period of six months following initial hospitalisation were both associated with a lower long-term risk. CONCLUSION: Non-ST elevation acute coronary syndromes carry a high risk of death over a 4-year period. Conventional risk factors can predict both short- and long-term risk. More invasive management and the use of evidence-based therapies appear to be associated with a lower risk.