Randomized trial of ticagrelor vs. aspirin in patients after coronary artery bypass grafting: the TiCAB trial.

AIMS: The antiplatelet treatment strategy providing optimal balance between thrombotic and bleeding risks in patients undergoing coronary artery bypass grafting (CABG) is unclear. We prospectively compared the efficacy of ticagrelor and aspirin after CABG. METHODS AND RESULTS: We randomly assigned in double-blind fashion patients scheduled for CABG to either ticagrelor 90 mg twice daily or 100 mg aspirin (1:1) once daily. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), repeat revascularization, and stroke 12 months after CABG. The main safety endpoint was based on the Bleeding Academic Research Consortium classification, defined as BARC ≥4 for periprocedural and hospital stay-related bleedings and BARC ≥3 for post-discharge bleedings. The study was prematurely halted after recruitment of 1859 out of 3850 planned patients. Twelve months after CABG, the primary endpoint occurred in 86 out of 931 patients (9.7%) in the ticagrelor group and in 73 out of 928 patients (8.2%) in the aspirin group [hazard ratio 1.19; 95% confidence interval (CI) 0.87-1.62; P = 0.28]. All-cause mortality (ticagrelor 2.5% vs. aspirin 2.6%, hazard ratio 0.96, CI 0.53-1.72; P = 0.89), cardiovascular death (ticagrelor 1.2% vs. aspirin 1.4%, hazard ratio 0.85, CI 0.38-1.89; P = 0.68), MI (ticagrelor 2.1% vs. aspirin 3.4%, hazard ratio 0.63, CI 0.36-1.12, P = 0.12), and stroke (ticagrelor 3.1% vs. 2.6%, hazard ratio 1.21, CI 0.70-2.08; P = 0.49), showed no significant difference between the ticagrelor and aspirin group. The main safety endpoint was also not significantly different (ticagrelor 3.7% vs. aspirin 3.2%, hazard ratio 1.17, CI 0.71-1.92; P = 0.53). CONCLUSION: In this prematurely terminated and thus underpowered randomized trial of ticagrelor vs. aspirin in patients after CABG no significant differences in major cardiovascular events or major bleeding could be demonstrated. CLINICALTRIALS.GOV IDENTIFIER: NCT01755520.

Effect of platelet inhibition with cangrelor during PCI on ischemic events.

BACKGROUND: The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects. METHODS: In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. RESULTS: The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P=0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P=0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P=0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups. CONCLUSIONS: Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.).

A randomized, parallel group, double-blind study of ticagrelor compared with aspirin for prevention of vascular events in patients undergoing coronary artery bypass graft operation: Rationale and design of the Ticagrelor in CABG (TiCAB) trial: An Investigator-Initiated trial.

BACKGROUND: For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial. HYPOTHESIS: Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG. STUDY DESIGN: The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled. SUMMARY: There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.

The role of endosonography in cardiology: case series and literature review.

Aims: Endosonography (EUS) is the diagnostic tool with the highest resolution for the local staging of gastrointestinal tumours and, due to the detailed visualization of the wall layers, is recommended in current guidelines for cancer management. In addition, an endoscope has an ultrasound tip design and balloon insufflation control design, and a 120° bending mechanism to deflect the endoscope tip. These advantages could be beneficial and valuable while investigating the cardiovascular structures during routine gastrointestinal procedures using this diagnostic tool. Methods and results: We present six cases of incidentally diagnosed cardiac pathologies (pulmonary thromboembolism of the main pulmonary artery, patent foramen oval with right to left shunt under Valsalva, left atrial appendage thrombus, aortic dissection, moderate aortic valve stenosis, mitral and aortic valve endocarditis) during routine gastrointestinal endosonographic procedures. These diagnoses influenced changes in management strategies in four cases. Conclusion: The introduction of EUS in cardiovascular medicine allows for a real-time high-resolution assessment of cardiovascular structures and allows early detection of silent cardiac pathologies during routine gastrointestinal procedures. It is the diagnostic tool with the highest resolution for accurate definition of variable gastrointestinal anatomy. Thus, help for accurate definitions of cardiovascular anatomy and pathology, which could influence optimal management strategies with improved safety, efficacy, and economic outcomes.

Elevation of matrix metalloproteinases in different areas of ascending aortic aneurysms in patients with bicuspid and tricuspid aortic valves.

Our aim is to investigate the elevation of matrix proteins in tissues obtained from distal, above the sinotubular junction (proximal), concave, and convex sites of aneurysms in the ascending aorta using a simultaneous multiplex protein detection system. Tissues were collected from 41 patients with ascending aortic aneurysms. A total of 31 patients had a bicuspid aortic valve (BAV), whereas 10 had a tricuspid aortic valve (TAV). Concave and convex aortic site samples were collected from all patients, whereas proximal and distal convexity samples were obtained from 19 patients with BAV and 7 patients with TAV. Simultaneous detection of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was performed at each of the four aortic sites. MMP-2 levels were higher in the concave aortic sites than in the convex aortic sites. In contrast, MMP-8 levels were higher in the convex sites than in the concave sites, as were MMP-9 levels. In both BAV and TAV patients, TIMP-3 levels were higher in the concave sites than in the convex sites. However, TIMP-2 and TIMP-4 levels were significantly elevated in the sinotubular proximal aorta of BAV patients. Simultaneous detection of MMPs and TIMPs revealed different levels at different aortic sites in the same patient.

Prognostic impact of secondary prevention after coronary artery bypass grafting-insights from the TiCAB trial.

OBJECTIVES: There are disparities in the adherence to guideline-recommended therapies after coronary artery bypass graft (CABG). We therefore sought to evaluate the effect of guideline-adherent medical secondary prevention on 1-year outcome after CABG. METHODS: Data were taken from the randomized 'Ticagrelor in CABG' trial. From April 2013 until April 2017, patients who underwent CABG were included. For the present analysis, we compared patients who were treated with optimal medical secondary prevention with those where 1 or more of the recommended medications were missing. RESULTS: Follow-up data at 12 months were available in 1807 patients. About half (54%) of them were treated with optimal secondary prevention. All-cause mortality [0.5% vs 3.5%, hazard ratio (HR) 0.14 (0.05-0.37), P < 0.01], cardiovascular mortality [0.1% vs 1.7%, HR 0.06 (0.01-0.46), P = 0.007] and major adverse events [6.5% vs 11.5%, HR 0.54 (0.39-0.74), P < 0.01] were significantly lower in the group with optimal secondary prevention. The multivariable model for the primary end point based on binary concordance to guideline recommended therapy identified 3 independent factors: adherence to guideline recommended therapy [HR 0.55 (0.39-0.78), P < 0.001]; normal renal function [HR 0.99 (0.98-0.99), P = 0.040]; and off-pump surgery [HR 2.06 (1.02-4.18), P = 0.045]. CONCLUSIONS: Only every second patient receives optimal secondary prevention after CABG. Guideline adherent secondary prevention therapy is associated with lower mid-term mortality and less adverse cardiovascular events after 12 months.

[Acute myocardial infarction: diagnosis and treatment]. / Der akute Myokardinfarkt. Eine Ubersicht über Diagnostik und Therapie.

Acute ST-elevation myocardial infarction (STEMI) represents a cardiac emergency with a high early mortality. Over the last decades, prognosis of patients with STEMI has dramatically improved. This has primarily been a result of advances in coronary interventional techniques as well as medical therapy. Direct percutaneous recanalization of the infarct-related artery represents the gold standard in treating STEMI, specifically when performed within two hours after first medical contact. These timelines imply logistical challenges for ambulance and hospital services. Furthermore, the broad variety of antithrombotic (acetylsalicylic acid, P2Y12 and GPIIb/IIIa receptor antagonists) and antithrombin medication (heparins, direct thrombin inhibitors) requires a sound understanding of the current evidence, guidelines and the individual patient characteristics to offer optimal medical therapy to the individual patient.

Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute ST-segment elevation myocardial infarction undergoing immediate percutaneous coronary intervention.

OBJECTIVE: Mild therapeutic hypothermia (MTH) has been integrated into international resuscitation guidelines. In the majority of patients, sudden cardiac arrest is caused by myocardial infarction. This study investigated whether a combination of MTH with primary percutaneous coronary intervention (PCI) is feasible, safe, and potentially beneficial in patients after cardiac arrest due to acute myocardial infarction. DESIGN: Single-center observational study with a historical control group. SETTING: University clinic. PATIENTS: Thirty-three patients after cardiac arrest with ventricular fibrillation as initial rhythm and restoration of spontaneous circulation who remained unconscious at admission and presented with acute ST elevation myocardial infarction (STEMI). INTERVENTIONS: In 16 consecutive patients (2005-2006), MTH was initiated immediately after admission and continued during primary PCI. Seventeen consecutive patients who were treated in a similar 2-yr observation interval before implementation of MTH (2003-2004) served as a control group. Feasibility, safety, mortality, and neurologic outcome were documented. MEASUREMENTS AND MAIN RESULTS: Initiation of MTH did not result in longer door-to-balloon times compared with the control group (82 vs. 85 mins), indicating that implementation of MTH did not delay the onset of primary PCI. Target temperature (32-34 degrees C) in the MTH group was reached within 4 hrs, consistent with previous trials and suggesting that primary PCI did not affect the velocity of cooling. Despite a tendency to increased bleeding complications and infections, patients treated with MTH tended to have a lower mortality after 6 months (25% vs. 35%, p = .71) and an improved neurologic outcome as determined by a Glasgow-Pittsburgh Cerebral Performance Scale score of 1 or 2 (69% vs. 47% in the control group, p = .30). CONCLUSIONS: MTH in combination with primary PCI is feasible and safe in patients resuscitated after cardiac arrest due to acute myocardial infarction. A combination of these therapeutic procedures should be strongly considered as standard therapy in patients after out-of-hospital cardiac arrest due to STEMI.

Association between arterial pressure and coronary artery calcification.

OBJECTIVES: Coronary artery calcification (CAC) determined by electron beam computed tomography is a predictor of future cardiovascular events. This study investigates conditions affecting CAC severity in patients with coronary artery disease (CAD) undergoing coronary angiography. METHODS: Presence and degree of CAC were assessed angiographically in 877 CAD patients grouped into no visible CAC (n = 333), mild to moderate CAC (n = 321), and severe CAC (n = 223). Regression analyses investigated relationships between CAC and demographic data, cardiovascular risk factors, and coronary anatomy. RESULTS: Prevalences of hypertension and systolic blood pressure (SBP) values were higher in individuals with CAC (moderate CAC: 49.5%, 137.5 +/- 18.6 mmHg; severe CAC: 58.3%, 142.1 +/- 20.4 mmHg) compared to individuals with CAD but no CAC (42.0%, 134.0 +/- 18.4 mmHg; both P < 0.001). Likewise, pulse pressure was significantly elevated with increasing degree of CAC (no CAC, 52.3 +/- 13.6 mmHg vs moderate CAC, 55.7 +/- 14.4 mmHg vs severe CAC, 59.1 +/- 15.4 mmHg; P < 0.001). Further determinants of CAC were age, positive family history for CAC and severity of CAD. No differences in CAC severity were found in relation to body mass index, low-density lipoprotein-cholesterol, diabetes, and smoking habits. In multivariate analysis, CAC was independently related to age, SBP or pulse pressure, respectively, positive family history for CAC, and the severity of CAD. CONCLUSIONS: Of the cardiovascular risk factors, SBP and pulse pressure display the strongest relationship with angiographic detection of CAC. Mechanistic studies need to clarify whether hypertension causes CAC, or whether coronary calcium deposition serves as a marker for a higher degree of vascular calcification and, thus, impaired vascular compliance and higher blood pressure levels.

Impact of the metabolic syndrome on angiographic and clinical events after coronary intervention using bare-metal or sirolimus-eluting stents.

Patients with metabolic syndrome (MS) are at increased risk for cardiovascular events. Although the number of patients with MS requiring coronary revascularization is increasing rapidly, the impact of MS on clinical events and restenosis in patients who undergo stent placement is not well defined. Seven hundred thirty-four consecutive patients with 734 de novo coronary lesions (<50 mm lesion length, reference vessel diameter <3.5 mm) were enrolled in this study. Four hundred thirty-seven patients were treated with bare-metal stents, and 297 patients were treated with sirolimus-eluting stents. Patients with bifurcation lesions, left main lesions, and ST-segment-elevation myocardial infarctions were excluded from the study. Patients were categorized into 3 groups: those with (1) diabetes mellitus (DM), (2) MS without DM, and (3) no MS and no DM. MS was defined according to American Heart Association and National Heart, Lung, and Blood Institute criteria (the presence of > or =3 of the following criteria: obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, and increased fasting glucose). Clinical follow-up was performed for > or =1 year (mean 27.5 +/- 18.1 months). One hundred sixty-four patients (22%) had DM, 180 patients (25%) had MS without DM, and 390 patients (53%) had no MS and no DM. Baseline clinical and angiographic parameters were comparable among the 3 groups, including lesion length and reference vessel diameter. In patients treated with bare-metal stents, the rates of major adverse cardiac events (MACEs) at 12 months were 14% in patients without DM or MS, 18% in those with MS but no DM, and 33% in those with DM (p = 0.046). In patients treated with sirolimus-eluting stents, the MACE rates were 3% in patients without DM or MS, 4% in those with MS, and 13% in those with DM (p = 0.034). DM (odds ratio 2.14, 95% confidence interval 1.48 to 3.07, p <0.001) and bare-metal stent (odds ratio 2.51, 95% confidence interval 1.49 to 4.22, p <0.001) implantation were independent predictors of MACEs during follow-up, whereas MS was not predictive. Similarly, MS was not a predictor of target lesion revascularization. In conclusion, patients with MS did not have an increased risk for target lesion revascularization or a greater MACE rate compared with control patients during a 12 month follow-up period after bare-metal or drug-eluting stent placement. In contrast, DM is associated with significantly increased event rates.

Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis.

BACKGROUND: The frequency and potential differences between patients with apical ("typical") and midventricular ("atypical") ballooning have not been described. METHODS: Consecutive patients with the diagnosis of a troponin-positive acute coronary syndrome (ACS) were prospectively included into a registry (n = 3,265). Of those, 2,944 patients underwent left-heart catheterization and form the study population. Demographic, clinical, and angiographic data including assessment of microvascular dysfunction (Thrombolysis in Myocardial Infarction [TIMI] blush grade, corrected TIMI frame count), as well as clinical outcome were assessed in all patients. RESULTS: In patients with troponin-positive ACS, the frequency of transient cardiomyopathy was 1.2% (35 of 2,944 patients). Typical apical wall motion abnormality was observed in 21 of 35 patients (60%), as compared to an atypical (midventricular) pattern in 14 of 35 patients (40%). Both groups did not differ regarding demographic, clinical, laboratory, or angiographic parameters. Scintigraphy and PET studies were performed in 17 of 35 patients (49%) with transient cardiomyopathy, and showed a strong correlation between location of wall motion abnormality and myocardial metabolism defects, with a significantly higher apical decrease in glucose uptake in patients with a typical pattern. CONCLUSIONS: Transient cardiomyopathy affects approximately 1% of patients with a troponin-positive ACS. A typical apical wall motion abnormality is seen in only 60% of patients. Transient cardiomyopathy, also termed Tako-Tsubo cardiomyopathy, therefore should no longer be regarded as an exclusively apical ballooning syndrome, but rather a transient left ventricular dysfunction syndrome with an apical or midventricular pattern of wall motion abnormality.

Mild therapeutic hypothermia after cardiac arrest - a nationwide survey on the implementation of the ILCOR guidelines in German intensive care units.

AIM: To investigate the implementation of mild therapeutic hypothermia (MTH) after cardiac arrest into clinical practice. METHODS AND RESULTS: A structured evaluation questionnaire was sent to all German hospitals registered to have ICUs; 58% completed the survey. A total of 93 ICUs (24%) reported to use MTH. Of those, 93% started MTH in patients after out-of-hospital resuscitation with observed ventricular fibrillation and 72% when other initial rhythms were observed. Only a minority of ICUs initiate MTH in patients after cardiac arrest with cardiogenic shock (28%), whereas 48% regarded cardiogenic shock as a contra-indication for MTH. On average, target temperature was 33.1+/-0.6 degrees C and duration of cooling 22.9+/-4.9 h. Many centres used economically priced cold packs (82%) and cold infusions (80%) for cooling. The majority of the ICUs considered infection, hypotension and bleeding as relevant complications of hypothermia which was of therapeutic relevance in less than 25% of the cases. CONCLUSIONS: MTH is underused in German ICUs. Centres which use MTH widely follow the recommendations of ILCOR with respect to the indication and timing of cooling. In hospitals that use MTH the technique is considered to be safe and inexpensive. More efforts are needed to promote this therapeutic option and hypothermia since MTH has now been included into European advanced cardiovascular life support protocols.

Thienopyridines in percutaneous coronary interventions: standard procedures and high risk subsets.

Due to the significant clinical and economic consequences of subacute stent thrombosis and the use of more complex devices (brachytherapy, drug eluting stents) in a variety of clinical situations (i.e. acute coronary syndromes), initiation and duration of a combined antiplatelet therapy using aspirin and a thienopyridine drug has become an issue of ongoing discussion in interventional cardiology. This review will provide a short introduction into the pathophysiology of stent thrombosis before standard procedures and critical issues on the use of thienopyridines in the setting of coronary interventions are discussed. Furthermore, clinically relevant issues that are not clearly covered by recommendations or guidelines like thienopyridines after coronary interventions in patients on chronic oral anticoagulation are also addressed.

Association of C-reactive protein and myocardial perfusion in patients with ST-elevation acute myocardial infarction.

This study sought to evaluate the relation between C-reactive protein (CRP) on admission of patients with acute myocardial infarction (AMI) and myocardial perfusion as defined by postintervention angiographic myocardial blush grade (MBG) and their impact on subsequent mortality. The patient population comprised 191 consecutive patients with AMI undergoing PTCA within 12h of symptom onset on a native vessel. Patients were divided based on the CRP level on admission (Rolf Greiner BioChemica, Germany, cutpoint for the assay CRP: 5mg/l) into a group with elevated CRP (>or=5mg/l) and a group with normal CRP. Angiographic myocardial blush grade (MBG) after revascularization of the infarct-related artery was determined to evaluate myocardial reperfusion. Revascularization of the infarct-related artery was successful in 176 (92.6%) patients. The frequency of impaired perfusion (MBG 0-2) was higher in the elevated CRP group than in the normal CRP group (74.5% versus 59.7%, respectively, p=0.046). Elevated CRP on admission was an independent predictor of impaired myocardial perfusion (MBG 0-2, OR 1.92, 95% CI 1.02-4.01, p=0.042) in addition to age >70 years. Elevated CRP (OR 2.64, 95% CI 1.26-5.53, p=0.009) and MBG 0-2 (OR 4.58; 95% 1.73-12.20, p=0.002) were independent predictors of mortality during a 22.4+/-15.3 months follow-up in addition to heart rate on admission >100 beats/min (OR 3.07; 95% CI 1.30-7.25, p=0.009). In sequential Cox models, the predictive power of clinical data and MBG for mortality (model chi-squared 18.3) was strengthened by the inclusion of CRP levels (model chi-squared 24.3). In conclusion, there is a relation between elevated admission CRP and impaired reperfusion in the myocardium subtended to the infarct-related artery. The combination of clinical data, myocardial reperfusion levels after primary angioplasty for AMI and admission CRP increases the predictive value for subsequent survival.

A double-blind, randomized, placebo-controlled multicenter clinical trial to evaluate the effects of the angiotensin II receptor blocker candesartan cilexetil on intimal hyperplasia after coronary stent implantation.

BACKGROUND: Preclinical data suggest beneficial effects of angiotensin II receptor blockers (ARBs) on neointima formation after vascular injury. Preliminary clinical data, however, revealed conflicting results. The AACHEN trial was a double-blind, randomized, placebo-controlled clinical multicenter trial to evaluate the effects of candesartan cilexetil on intimal hyperplasia after coronary stent implantation. METHODS: A total of 120 patients (61 +/- 9 years, 83% male) were randomized to receive either 32 mg candesartan cilexetil (active) or placebo starting 7 to 14 days before elective coronary stent implantation. A follow-up angiography including intravascular ultrasound assessment of the target lesion was performed 24 +/- 2 weeks after stent implantation. The primary end point was defined as the difference in neointimal area between groups as assessed by intravascular ultrasound. Secondary end points included differences in angiographic parameters (ie, restenosis rate) and incidence of major cardiac events. RESULTS: The mean stent length measured 15.0 +/- 4.9 mm in the active and 14.6 +/- 5.7 mm in the placebo group (P = .81). There was no significant difference in neointimal area between groups (2.1 +/- 1.0 vs 2.1 +/- 1.5 mm2, P = 1.00), nor were there differences in angiographic end point parameters. Major cardiac event rates were not significantly different between treatment groups (8% vs 11%, P = .75). CONCLUSIONS: High-dose candesartan cilexetil therapy in patients with symptomatic coronary artery disease undergoing coronary stent implantation does not reduce clinical event rates, restenosis rates, or neointimal proliferation after elective stent implantation.

Comparison of coronary restenosis rates in matched patients with versus without diabetes mellitus.

Diabetes mellitus (DM) is an established risk factor for stent restenosis, in part as a result of the smaller vessel dimensions and longer lesions. This study compared the magnitude of acute lumen gain and late lumen loss after elective coronary stent implantation in patients with and without DM using a matched-pair analysis. A total of 133 patients with DM and 192 coronary lesions were included in this analysis. A group of 192 lesions in 182 patients without DM were matched in a pairwise fashion, stratifying for reference diameter, minimal luminal diameter, and lesion length. The binary restenosis rate at the 5-month follow-up angiography was 25% in the DM group and 14% in the non-DM group (p <0.01). Acute angiographic lumen gain (1.47 +/- 0.41 vs 1.56 +/- 0.38 mm, p = 0.03) and late lumen loss (0.64 +/- 0.42 vs 0.55 +/- 0.36 mm, p = 0.02) were significantly different between the DM and non-DM groups. In conclusion, suboptimal acute procedural results and an exaggerated neointimal proliferation contributed by about 50% to the lower net lumen gain in the DM group. Patients with DM had a significantly higher restenosis rate even when matched for preprocedural angiographic lesion dimensions. Mechanistically, inferior procedural results, as well as exaggerated neointimal proliferation, are, quantitatively, equally important in this process.

Evaluation of the porcine ameroid constrictor model of myocardial ischemia for therapeutic angiogenesis studies.

The porcine ameroid model of chronic myocardial ischemia has been widely used for the evaluation of coronary collateralization development. The impact of target vessel occlusion on the presence of myocardial ischemia, and the relationship between morphological, functional, and hemodynamic measurements in the context of therapeutic angiogenesis studies, however, has not been studied thus far. The authors therefore performed a systematic analysis of 94 animals undergoing ameroid constrictor placement around the left circumflex coronary artery (LCX) and, furthermore, a comprehensive evaluation including echocardiography and coronary angiography 26 +/- 1 (mean +/- SEM) days after ameroid placement. Complete LCX occlusion was observed in 34/94 animals (36%) and identified those with myocardial ischemia of the lateral wall, both at rest and under pharmacological stress. By applying a set of angiographic criteria (TIMI or= 1), another 27/94 animals with myocardial ischemia under conditions of pharmacological stress conditions could be identified. Interestingly, echocardiographic parameters of regional and global myocardial function were not correlated with myocardial blood flow or the degree of ischemia. There was no relationship between the extent of coronary collateralization, as assessed by angiography, echocardiographic parameters, or myocardial blood flow. The authors therefore conclude that complete occlusion of the ameroid instrumented coronary artery is not a prerequisite for successfully establishing the pathophysiology of myocardial ischemia. Defined angiographic criteria are important in identifying ischemic animals, thus reducing total animal numbers. Angiographic assessment of the degree of coronary collateralization, however, is not associated with myocardial blood flow or function and should not be used as a primary outcome measure of therapeutic angiogenesis studies in this model.