B Meier

THROMBOLYSIS WITH TISSUE PLASMINOGEN ACTIVATOR IN ACUTE MYOCARDIAL INFARCTION: NO ADDITIONAL BENEFIT FROM IMMEDIATE PERCUTANEOUS CORONARY ANGIOPLASTY

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarct-related segment, but this was offset by a high rate of transient (16%) and sustained (7%) reocclusion during the procedure and recurrent ischaemia during the first 24 h (17%). The clinical course was more favourable after non-invasive therapy, with a lower incidence of recurrent ischaemia within 24 h (3%), bleeding complications, hypotension, and ventricular fibrillation. Mortality at 14 days was lower in patients allocated to non-invasive treatment (3%) than in the group allocated to invasive treatment (7%). No difference between the treatment groups was observed in infarct size estimated from myocardial release of alpha-hydroxybutyrate dehydrogenase or in left ventricular ejection fraction after 10-22 days. Since immediate PTCA does not provide additional benefit there seems to be no need for immediate angiography and PTCA in patients with acute myocardial infarction treated with rTPA.

Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial

BACKGROUND A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). METHODS We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26). INTERPRETATION Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. FUNDING Biosensors Europe SA, Switzerland.

Percutaneous closure of patent foramen ovale: impact of device design on safety and efficacy

Objective: To compare the safety and efficacy of percutaneous closure of patent foramen ovale (PFO) with the Amplatzer PFO occluder (Amplatzer) or the PFO STAR device (STAR) in patients with presumed paradoxical embolism. Methods: Implantation characteristics, procedural complications, residual shunt, and recurrence of thromboembolic events were recorded prospectively in 100 consecutive patients undergoing percutaneous PFO closure with the STAR (n  =  50) or Amplatzer (n  =  50) devices between 1998 and 2001. The study was not randomised. Device implantation was successful in all cases. Results: There were more procedural complications in the STAR than in the Amplatzer group (8/50 v 1/50, p  =  0.01). More than one device placement attempt was an independent predictor of procedural complications (odds ratio (OR) 8.5, 95% confidence interval (CI) 1.3 to 55.8; p  =  0.03). A residual shunt six months after PFO closure, assessed by transoesophageal contrast echocardiography, occurred more often in the STAR than the Amplatzer group (17/50 v 3/50, p  =  0.004), and was predicted in the STAR group by the use of a device with a 5 mm as opposed to a 3 mm disc connector (OR 6.1, 95% CI 1.1 to 34.0; p  =  0.04). The actuarial risk of recurrent thromboembolic events after 3.5 years was 16.8% (95% CI 7.6% to 34.6%) in the STAR and 2.7% (95% CI 0.4% to 17.7%) in the Amplatzer group after three years (p  =  0.08). Conclusions: Percutaneous PFO closure with the Amplatzer PFO occluder had fewer procedural complications and was more likely to be complete than with the STAR device. These findings underline the importance of device design for successful percutaneous PFO closure.

Efficacy of drug eluting stents in patients with and without diabetes mellitus: indirect comparison of controlled trials

Objective: To examine whether polymer based coronary stents eluting sirolimus or paclitaxel are equally effective in patients with and without diabetes. Methods: Systematic review and meta-analysis by indirect comparison of randomised controlled trials comparing stents eluting sirolimus or paclitaxel with conventional bare metal stents. The overall study population and patients with and without diabetes were analysed separately by using the ratio of incidence rate ratios (RIRR). Results: The analysis was based on 10 trials (six with sirolimus, four with paclitaxel), 4513 patients (1146 patients with diabetes), 5755 years of follow up, and 2464 events. In patients without diabetes sirolimus eluting stents were superior to paclitaxel eluting stents with respect to in-stent (RIRR 0.21, 95% confidence interval (CI) 0.10 to 0.48, p < 0.001) and in-segment restenosis (RIRR 0.47, 95% CI 0.24 to 0.92, p  =  0.027), target lesion revascularisation (RIRR 0.54, 95% CI 0.30 to 0.99, p  =  0.045), and major adverse cardiac events (RIRR 0.46, 95% CI 0.26 to 0.83, p  =  0.010). In patients with diabetes the two drug eluting stents did not differ significantly in any of these end points. Meta-regression analysis showed a significant difference between patients with and without diabetes (tests for interaction for in-stent and in-segment restenosis, p  = 0.036 and p  =  0.016). Conclusion: Indirect evidence indicates that sirolimus eluting stents are superior to paclitaxel eluting stents in patients without diabetes but not in patients with diabetes.

Clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting. Implications for mechanical plaque sealing

AIMS To investigate the clinical and angiographic outcome of patients with mild coronary lesions treated with balloon angioplasty or coronary stenting (coronary plaque sealing, i.e. dilatation of angiographically non-significant lesions) compared to moderate and severe stenoses. METHODS AND RESULTS Patients with chronic stable angina and a single de novo lesion in a native coronary vessel scheduled to undergo percutaneous coronary intervention (PCI) were selected from 14 different studies. Off-line analysis of angiographic outcomes was assessed in all patients using identical and standardised methods of data acquisition, analysis and definitions. Clinical endpoints were adjudicated by independent clinical events committees. All quantitative coronary angiographic (QCA) analyses were performed in the same core laboratory. Stenosis severity prior to PCI was categorised into three groups: <50% diameter stenosis (DS), 50-99%DS and >99%DS pre. A total of 3812 patients were included in this study; 1484 patients (39%) were successfully treated with balloon angioplasty (BA) only and stented angioplasty was performed in 2328 patients (61%).One-year mortality and rate of non-fatal myocardial infarction (MI) (Kaplan-Meier) did not differ between BA and stented angioplasty for any of the stenosis severity categories. Following BA, the combined event rate (death and non-fatal MI) was 4.8, 4.6 and 0% in the <50, 50-99 and >99%DS categories, respectively. Following stented angioplasty, the combined event rate was 3.1, 4.4 and 4.8% in the same categories. The need for repeat revascularisation corrected for stenosis severity in the Cox proportional-hazards regression model was reduced by 20% after stented angioplasty (hazard ratio (HR) 0.80, 95%CI 0.69-0.93). CONCLUSION The concept of plaque sealing is appealing from the theoretical point of view. However, with current technology, plaque sealing cannot prevent death and future non-fatal MIs in the long-term because 1-year event rates after PCI of non-significant stenoses remain unacceptably elevated when compared with the estimated 1-year probability of a non-fatal MI in lesions with a <50%DS. Moreover, major adverse cardiac events at 1-year after PCI are not directly related to the degree of pre-procedural stenosis severity.

Influence of diabetes mellitus on coronary collateral flow: an answer to an old controversy

Objectives: To determine the influence of diabetes mellitus on coronary collateral flow by accurate means of collateral flow measurement in a large population with variable degrees of coronary artery disease. Methods: 200 patients (mean (SD) age 64 (9) years; 100 diabetic and 100 non-diabetic) were enrolled in the study. Coronary collateral flow was assessed in 174 stenotic and in 26 angiographically normal vessels with a pressure guidewire (n  =  131), Doppler guidewire (n  =  36), or both (n  =  33) to calculate pressure or flow velocity derived collateral flow index (CFI). Diabetic patients were perfectly matched with a non-diabetic control group for clinical, haemodynamic, and angiographic parameters. Results: CFI did not differ between the diabetic and the non-diabetic patients (0.21 (0.12) v 0.19 (0.13), not significant). Likewise, CFI did not differ when only angiographically normal vessels (0.20 (0.09) v 0.15 (0.08), not significant) or chronic total coronary occlusions (0.30 (0.14) v 0.30 (0.17), not significant) were compared. Fewer patients in the diabetic group tended to have angina pectoris during the one minute vessel occlusion (60 diabetic v 69 non-diabetic patients, p  =  0.15). Conclusion: Quantitatively measured coronary CFI did not differ between diabetic and non-diabetic patients with stable coronary artery disease.

Washout collaterometry: a new method of assessing collaterals using angiographic contrast clearance during coronary occlusion

OBJECTIVE To investigate the hypothesis that the time to washout of radiographic contrast medium trapped distal to an occluded collateral receiving vessel is inversely related to collateral flow, and that this provides an accurate method for characterising coronary collaterals. METHODS An intracoronary pressure derived collateral flow index was determined in 54 patients undergoing percutaneous transluminal coronary balloon angioplasty (PTCA). The study group was subdivided according to whether the collateral vessels were sufficient (n = 17) or insufficient (n = 37) to prevent ECG signs of myocardial ischaemia during PTCA. Washout collaterometry—an angiographic washout method—was carried out simultaneously; after injection of radiographic contrast medium into the collateral receiving vessel followed immediately by vascular occlusion, the number of heart beats was counted until approximately half the length of the epicardial vessel was cleared of contrast. RESULTS The collateral flow index was higher (0.28 (0.09) v 0.12 (0.07); p < 0.0001) and the contrast washout time shorter (8.0 (2.9)v 17.5 (6.7) heart beats; p < 0.0001) in patients with sufficient versus insufficient collaterals. There was an inverse correlation between contrast washout time and collateral flow index (r = 0.72, p < 0.0001). Washout of contrast distal to the occluded vessel within 11 heart beats correctly determined sufficient and insufficient collaterals with 88% sensitivity and 81% specificity. CONCLUSIONS Washout collaterometry is a new radiographic contrast washout method based on the inverse relation between collateral flow and the time to clearance of radiographic dye injected into the ipsilateral vessel during PTCA. It appears to be an accurate method of characterising coronary collateral vessels.

Influence on collateral flow of recanalising chronic total coronary occlusions: a case-control study

OBJECTIVE To assess the effect of recanalisation on collateral flow in a case–control study in patients with and without chronic total coronary occlusions. DESIGN In 54 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) (mean (SD) age 61 (6) years), coronary collateral flow was measured by intracoronary pressure or Doppler guide wires at the end of repeated balloon occlusions. Coronary collateral flow index (collateral flow relative to normal antegrade flow) during the first two balloon inflations in 27 patients with a chronic total occlusion (occlusion group) was compared with that of 27 patients matched for age, sex, and collateral flow index at the first occlusion and with a coronary artery diameter stenosis ⩽ 80% (stenosis group). RESULTS Following revascularisation, collateral flow index decreased in 17 of the patients in the occlusion group (63%) and in eight of the patients in the stenosis group (30%) (p = 0.03 between groups). The overall change of collateral flow index between the first and the second balloon occlusion was −0.04 (0.01) in the occlusion group (p = 0.07 for paired comparison; from 0.29 (0.17) to 0.25 (0.14)), and +0.02 (0.06) in the stenosis group (p = 0.06 for paired comparison; from 0.27 (0.13) to 0.30 (0.15)). The trend to collateral enhancement in the stenosis group differed significantly from the occlusion group (p = 0.01). CONCLUSIONS While repeated coronary balloon occlusions induce collateral recruitment in the majority of patients with moderate stenoses, recanalisation of chronic total coronary occlusions is more often associated with collateral flow reduction. A later decrease in collateral flow by involution of collateral channels cannot be excluded by this study but has not been reported so far.

Effect of statin treatment on coronary collateral flow in patients with coronary artery disease

Recent work has suggested an angiogenic,1 and conversely, an angiostatic2 or biphasic effect of statins.3 However, such hypotheses have been tested only in vitro or in animal models. The influence of statins on human arteriogenesis, the formation of collateral arteries, nowadays thought to be necessary to save myocardium from ischaemia, has not been previously investigated. Five hundred patients with stable one to three vessel coronary artery disease (CAD) and without Q wave myocardial infarction underwent quantitative assessment of the coronary collateral circulation during coronary angioplasty. The patients were divided into two different groups according to the use of statins (termed “statin group”, n  =  186) or the absence of statin treatment (termed “no statin group”, n  =  314). All patients underwent left heart catheterisation, including biplane left ventricular angiography and coronary angiography for diagnostic purposes. Aortic pressure was recorded using the angioplasty catheter. Coronary artery stenoses were assessed quantitatively as per cent lumen diameter reduction, using the guiding catheter for calibration. Collateral vessel assessment was performed by three …

The MI SYNTAX score for risk stratification in patients undergoing primary percutaneous coronary intervention for treatment of acute myocardial infarction: A substudy of the COMFORTABLE AMI trial

BACKGROUND To investigate the performance of the MI Sxscore in a multicentre randomised trial of patients undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS The MI Sxscore was prospectively determined among 1132 STEMI patients enrolled into the COMFORTABLE AMI trial, which randomised patients to treatment with bare-metal (BMS) or biolimus-eluting (BES) stents. Patient- (death, myocardial infarction, any revascularisation) and device-oriented (cardiac death, target-vessel MI, target lesion revascularisation) major adverse cardiac events (MACEs) were compared across MI Sxscore tertiles and according to stent type. The median MI SXscore was 14 (IQR: 9-21). Patients were divided into tertiles of Sxscorelow (≤10), Sxscoreintermediate (11-18) and Sxscorehigh (≥19). At 1 year, patient-oriented MACE occurred in 15% of the Sxscorehigh, 9% of the Sxscoreintermediate and 5% of the Sxscorelow tertiles (p<0.001), whereas device-oriented MACE occurred in 8% of the Sxscorehigh, 6% of the Sxscoreintermediate and 4% of the Sxscorelow tertiles (p=0.03). Addition of the MI Sxscore to the TIMI risk score improved prediction of patient- (c-statistic value increase from 0.63 to 0.69) and device-oriented MACEs (c-statistic value increase from 0.65 to 0.70). Differences in the risk for device-oriented MACE between BMS and BES were evident among Sxscorehigh (13% vs. 4% HR 0.33 (0.15-0.74), p=0.007 rather than those in Sxscorelow: 4% vs. 3% HR 0.68 (0.24-1.97), p=0.48) tertiles. CONCLUSIONS The MI Sxscore allows risk stratification of patient- and device-oriented MACEs among patients undergoing PPCI. The addition of the MI Sxscore to the TIMI risk score is of incremental prognostic value among patients undergoing PPCI for treatment of STEMI.