Effect of rosiglitazone on progression of atherosclerosis: insights using 3D carotid cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>There is recent evidence suggesting that rosiglitazone increases death from cardiovascular causes. We investigated the direct effect of this drug on atheroma using 3D carotid cardiovascular magnetic resonance.</p> <p>Results</p> <p>A randomized, placebo-controlled, double-blind study was performed to evaluate the effect of rosiglitazone treatment on carotid atherosclerosis in subjects with type 2 diabetes and coexisting vascular disease or hypertension. The primary endpoint of the study was the change from baseline to 52 weeks of carotid arterial wall volume, reflecting plaque burden, as measured by carotid cardiovascular magnetic resonance. Rosiglitazone or placebo was allocated to 28 and 29 patients respectively. Patients were managed to have equivalent glycemic control over the study period, but in fact the rosiglitazone group lowered their HbA1c by 0.88% relative to placebo (P < 0.001). Most patients received a statin or fibrate as lipid control medication (rosiglitazone 78%, controls 83%). Data are presented as mean ± SD. At baseline, the carotid arterial wall volume in the placebo group was 1146 ± 550 mm³and in the rosiglitazone group was 1354 ± 532 mm³. After 52 weeks, the respective volumes were 1134 ± 523 mm³and 1348 ± 531 mm³. These changes (-12.1 mm³and -5.7 mm³in the placebo and rosiglitazone groups, respectively) were not statistically significant between groups (P = 0.57).</p> <p>Conclusion</p> <p>Treatment with rosiglitazone over 1 year had no effect on progression of carotid atheroma in patients with type 2 diabetes mellitus compared to placebo.</p

Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Single-Vessel Coronary Artery Disease: Physiology-Stratified Analysis of ORBITA

BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR (Pinteraction=0.318) or iFR (Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR (Pinteraction<0.00001) and decreasing iFR (Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR (Pinteraction=0.849) or iFR (Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR (Pinteraction=0.693) nor iFR (Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI

Placebo-controlled efficacy of percutaneous coronary intervention for focal and diffuse patterns of stable coronary artery disease

Background: Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom end points. Methods: One hundred sixty-four patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment before randomization. Focal disease was defined as a ≥0.03 iFR unit drop within 15 mm, rather than over a longer distance. Analyses were performed using regression modeling. Results: In the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (mean FFR and iFR, focal 0.60±0.15 and 0.65±0.24, diffuse 0.78±0.10 and 0.88±0.08, respectively, P<0.0001). With adjustment for this difference, PCI for focal stenoses resulted in significantly greater reduction in stress echo ischemia than PCI for diffuse disease (P<0.05). The effect of PCI on between-arm pre-randomization adjusted exercise time was 9.32 seconds (95% CI, −17.1 to 35.7 seconds; P=0.487). When stratified for pattern of disease, there was no detectable difference between focal and diffuse CAD (Pinteraction=0.700). PCI improved Seattle Angina Questionnaire angina frequency score and freedom from angina more than placebo (P=0.034; P=0.0035). However, there was no evidence of interaction between the physiological pattern of CAD and these effects (Pinteraction=0.436; Pinteraction=0.908). Conclusions: PCI achieved significantly greater reduction of stress echocardiography ischemia in focal compared with diffuse CAD. However, for symptom end points, no such difference was observed

Dobutamine stress echocardiography ischemia as a predictor of the placebo-controlled efficacy of percutaneous coronary intervention in stable coronary artery disease: the stress echo-stratified analysis of ORBITA

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina).METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling.RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426).CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI

Regional variation in cardiovascular magnetic resonance service delivery across the UK.

OBJECTIVES To examine service provision in cardiovascular magnetic resonance (CMR) in the UK. Equitable access to diagnostic imaging is important in healthcare. CMR is widely available in the UK, but there may be regional variations. METHODS An electronic survey was sent by the British Society of CMR to the service leads of all CMR units in the UK in 2019 requesting data from 2017 and 2018. Responses were analysed by region and interpreted alongside population statistics. RESULTS The survey response rate was 100% (82 units). 100 386 clinical scans were performed in 2017 and 114 967 in 2018 (15% 1-year increase; 5-fold 10-year increase compared with 2008 data). In 2018, there were 1731 CMR scans/million population overall, with significant regional variation, for example, 4256 scans/million in London vs 396 scans/million in Wales. Median number of clinical scans per unit was 780, IQR 373-1951, range 98-10 000, with wide variation in mean waiting times (median 41 days, IQR 30-49, range 5-180); median 25 days in London vs 180 days in Northern Ireland). Twenty-five units (30%) reported mean elective waiting times in excess of 6 weeks, and 8 (10%) ≥3 months. There were 351 consultants reporting CMR, of whom 230 (66%) were cardiologists and 121 (34%) radiologists; 81% of units offered a CMR service for patients with pacemakers and defibrillators. CONCLUSIONS This survey provides a unique, contemporary insight into national CMR delivery with 100% centre engagement. The 10-year growth in CMR usage at fivefold has been remarkable but heterogeneous across the UK, with some regions still reporting low usage or long waiting times which may be of clinical concern