Clinical inertia in basal insulin-treated patients with type 2 diabetes - Results from a retrospective database study in Japan (JDDM 43).

AIMS: This retrospective cohort study investigated whether clinical inertia, the failure to intensify treatment when required, exists in Japanese clinical practice, using the CoDiC® database. How and when patients with type 2 diabetes treated with basal insulin received treatment intensification was also described. MATERIALS AND METHODS: Patients with type 2 diabetes who initiated basal insulin between 2004 and 2011 were eligible for inclusion. Patients with an HbA1c ≥7.0% (≥53.0 mmol/mol) after 180 days of basal insulin titration were eligible for intensification, and their treatment was followed for up to 1.5 years. Endpoints were time to intensification, changes in HbA1c, and insulin dose. RESULTS: Overall, 2351 patients initiated basal insulin treatment (mean HbA1c 9.4% [79.2 mmol/mol]), and 1279 patients were eligible for treatment intensification (HbA1c ≥7.0% [≥53.0 mmol/mol]) after the 180-day titration period. During the 1.5-year follow-up period (beyond the 180-day titration period), 270 (21%) of these patients received treatment intensification. In patients receiving treatment intensification, mean HbA1c decreased from 8.6 to 8.2% (70.5 to 66.1 mmol/mol) at end of follow-up. Treatment was intensified using bolus insulin in 126 (47%) patients and with premixed insulin in 144 (53%) patients. The estimated probability of intensifying treatment during the 12 months after recording HbA1c ≥7.0% (≥53.0 mmol/mol) was 22.8%, and 27.5% after 17 months. Mean end-of-follow-up daily insulin dose was 35.11 units for basal-bolus compared with 20.70 units for premix therapy. CONCLUSIONS: This study suggests clinical inertia exists in basal insulin-treated patients with type 2 diabetes in Japan. Strategies are needed to increase the number of patients undergoing therapy intensification and to reduce the delay in intensification in Japan.

Stability and performance of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion: a systematic review.

AIM: We review and summarize the literature on the safety and stability of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion (CSII) in patients with diabetes. METHODS: Two predefined search strategies were systematically implemented to search Medline and the Cochrane Register of Clinical Trials for publications between 1996 and 2012. RESULTS: Twenty studies were included in the review: 13 in vitro studies and 7 clinical studies. In vitro studies investigated the effects of extreme CSII conditions (high temperature and mechanical agitation) on the risk of catheter occlusions and insulin stability factors, such as potency, purity, high molecular weight protein content, pH stability, and preservative content (m-cresol, phenol). Under these conditions, the overall stability of rapid-acting insulin analogs was similar for insulin lispro, insulin aspart, and insulin glulisine, although insulin glulisine showed greater susceptibility to insulin precipitation and catheter occlusions. A limited number of clinical trials were identified; this evidence-based information suggests that the rate of catheter occlusions in patients with type 1 diabetes using CSII treatment may vary depending on the rapid-acting analog used. CONCLUSIONS: Based on a limited amount of available data, the safety, stability, and performance of the three available rapid-acting insulin analogs available for use with CSII were similar. However, there is limited evidence suggesting that the risk of occlusion may vary with the insulin preparation under certain circumstances.

Sex- and age-related differences of myocardial perfusion at rest assessed with multidetector computed tomography.

BACKGROUND: The clinical presentation of ischemic heart disease in women differs from men, which could reflect sex-related differences of normal physiology. Cardiac CT angiography provides a noninvasive method to assess both regional and transmural myocardial perfusion in addition to coronary atherosclerosis. OBJECTIVE: The aim of this study was to evaluate potential sex-related differences of (1) left ventricular (LV) myocardial perfusion measured as LV myocardial attenuation density/LV blood pool attenuation density (MyoAD-ratio) at rest and (2) transmural perfusion ratio (TPR) as a measure of endocardial perfusion relative to epicardial perfusion. METHODS: Myocardial perfusion at rest and coronary artery atherosclerosis were evaluated with multidetector CT in 206 asymptomatic women and 203 age-matched men from the Copenhagen General Population Study. RESULTS: LV myocardial perfusion at rest (LV MyoAD-ratio) was higher in women than in men (9% difference; P = 0.039). In a multivariable analysis, including age, sex, cardiovascular risk factors, Agatston score, and presence of coronary stenosis, global LV MyoAD-ratio remained significantly higher in women than in men (P = 0.045). No effect of cardiovascular risk factors on myocardial perfusion at rest was noted. Myocardial perfusion at rest was correlated to age in men (r = 0.15, P = 0.031) but not in women (r = -0.01, P = 0.83). TPR was slightly lower in women than in men (1.12 vs 1.14; P = 0.0019). CONCLUSION: LV myocardial perfusion at rest is higher in women than men independent of coronary atherosclerosis in asymptomatic subjects with risk factors.

Hypercoagulability in relation to coronary artery bypass graft patency and clinical outcome.

OBJECTIVE: Hypercoagulability evaluated with thrombelastography (TEG) has been reported to be associated to thrombembolic events in patients undergoing coronary artery bypass graft surgery (CABG). The objective of this study was to test the hypothesis that graft patency and post-CABG thrombembolic events are related to the pre-surgical TEG status. DESIGN: 124 patients scheduled for CABG were matched according to mean age, gender and mean left ventricular ejection fraction in two groups defined by their pre-surgical TEG status (TEG-hypercoagulable and TEG-normocoagulable). Three months after the operation graft patency was assessed with multidetector computed tomography (MDCT). Major adverse cardiovascular and cerebral events (MACCE) were recorded for a median period of 7 months (range 3 to 37 months) after CABG. RESULTS: A total of 359 grafts were analyzed, 186 in TEG-hypercoagulable and 173 in TEG-normocoagulable patients. Frequency of bypass graft occlusion was not significantly different between the two groups (TEG-hypercoagulable = 21 and TEG-normocoagulable = 18, p = 0.9). The number of MACCE was significantly higher in the TEG-hypercoagulable compared to the TEG-normocoagulable group (TEG-hypercoagulable = 30% and TEG-normocoagulable = 9% p = 0.004). CONCLUSIONS: Hypercoagulability, as evaluated by TEG in patients undergoing CABG is associated with an increased risk of post-surgical thrombembolic events, however not accompanied by augmented coronary bypass graft failure.

Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial.

BACKGROUND: Hypercoagulability, assessed by the thrombelastography (TEG) assay, has in several observational studies been associated with an increased risk of post-procedural thromboembolic complications. We hypothesize that intensified antiplatelet therapy with clopidogrel and aspirin, as compared to aspirin alone, will improve saphenous vein graft patency in preoperatively TEG-Hypercoagulable coronary artery bypass surgery (CABG) patients and reduce their risk for thromboembolic complications and death postoperatively. METHODS/DESIGN: This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery. CONCLUSIONS: The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01046942.

Long-term internal thoracic artery bypass graft patency and geometry assessed by multidetector computed tomography.

The left internal thoracic artery (LITA) undergoes vascular remodelling when used for coronary artery bypass grafting. In this study we tested the hypothesis that the extent of the LITA remodelling late after coronary artery bypass grafting assessed by multidetector computed tomography is related to the severity of stenosis in the native coronary vessel. One hundred and forty-two patients who had undergone coronary artery bypass grafting including implantation of LITA as conduit to the left anterior descending artery were studied 5 years after surgery. Arterial graft patency and geometry was assessed with 64-slice multidetector computed tomography. Quantitative volumetric assessment of the LITA was performed to measure the average vessel lumen area (mm(2)/m(2)). The native coronary vessel subtended by the LITA was evaluated by multidetector computed tomography and defined as a high-grade stenosis patient group, when the diameter stenosis was >70% and an intermediate grade stenosis patient group when <70%. Among patients with intermediate-grade stenosis of the native vessel 11 out of 65 patients (17%) had a totally occluded LITA, as opposed to none among the 77 patients with a high-grade stenosis. In patients with intermediate-grade stenosis of the proximal native vessel, the LITA lumen area was 4.9 compared to 5.3 mm(2)/m(2) in patients with a high-grade stenosis of the proximal native vessel (P = 0.0043). Lumen area of the LITA when used as a conduit in patients with coronary artery disease seems to be inversely correlated with the severity of disease in the native coronary vessel proximal to the anastomosis. Volumetric vessel multidetector computed tomography appears to be useful for evaluation of coronary bypass remodelling.

[Coronary artery calcium score in cardiac CT increases the prognostic information of selected patients]. / Koronararteriecalciumscore ved hjertecomputertomografi øger den prognostiske information hos udvalgte personer.

Cardiovascular disease is the leading cause of death in the western countries. Conventional risk evaluation of asymptomatic individuals is unfortunately inaccurate. There is a need for better diagnostic tools to identify persons, who will benefit from intensified preventive treatment. Coronary artery calcium score (CACS) measured by multi-slice CT scan contributes significantly to risk stratification especially in persons with intermediate risk assessed by conventional risk analysis. A CACS-guided preventive intervention strategy seems appealing to reduce mortality due to cardiovascular disease.