Matti Niemelä

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial

BACKGROUNDnSmall trials have suggested that radial access for percutaneous coronary intervention (PCI) reduces vascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronary angiography with possible intervention.nnnMETHODSnThe RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group, multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voice response system to radial or femoral artery access. The primary outcome was a composite of death, myocardial infarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273.nnnFINDINGSnBetween June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries. 3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in 128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72-1·17; p=0·50). Of the six prespecified subgroups, there was a significant interaction for the primary outcome with benefit for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28-0·87; p=0·015) and in patients with ST-segment elevation myocardial infarction (0·60, 0·38-0·94; p=0·026). The rate of death, myocardial infarction, or stroke at 30 days was 112 (3·2%) of 3507 patients in the radial group compared with 114 (3·2%) of 3514 in the femoral group (HR 0·98, 95% CI 0·76-1·28; p=0·90). The rate of non-CABG-related major bleeding at 30 days was 24 (0·7%) of 3507 patients in the radial group compared with 33 (0·9%) of 3514 patients in the femoral group (HR 0·73, 95% CI 0·43-1·23; p=0·23). At 30 days, 42 of 3507 patients in the radial group had large haematoma compared with 106 of 3514 in the femoral group (HR 0·40, 95% CI 0·28-0·57; p<0·0001). Pseudoaneurysm needing closure occurred in seven of 3507 patients in the radial group compared with 23 of 3514 in the femoral group (HR 0·30, 95% CI 0·13-0·71; p=0·006).nnnINTERPRETATIONnRadial and femoral approaches are both safe and effective for PCI. However, the lower rate of local vascular complications may be a reason to use the radial approach.nnnFUNDINGnSanofi-Aventis, Population Health Research Institute, and Canadian Network for Trials Internationally (CANNeCTIN), an initiative of the Canadian Institutes of Health Research.

A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: The air primary angioplasty in myocardial infarction study

OBJECTIVESnThe Air Primary Angioplasty in Myocardial Infarction (PAMI) study was designed to determine the best reperfusion strategy for patients with high-risk acute myocardial infarction (AMI) at hospitals without percutaneous transluminal coronary angioplasty (PTCA) capability.nnnBACKGROUNDnPrevious studies have suggested that high-risk patients have better outcomes with primary PTCA than with thrombolytic therapy. It is unknown whether this advantage would be lost if the patient had to be transferred for PTCA, and reperfusion was delayed.nnnMETHODSnPatients with high-risk AMI (age >70 years, anterior MI, Killip class II/III, heart rate >100 beats/min or systolic BP <100 mm Hg) who were eligible for thrombolytic therapy were randomized to either transfer for primary PTCA or on-site thrombolysis.nnnRESULTSnOne hundred thirty-eight patients were randomized before the study ended (71 to transfer for PTCA and 67 to thrombolysis). The time from arrival to treatment was delayed in the transfer group (155 vs. 51 min, p < 0.0001), largely due to the initiation of transfer (43 min) and transport time (26 min). Patients randomized to transfer had a reduced hospital stay (6.1 +/- 4.3 vs. 7.5 +/- 4.3 days, p = 0.015) and less ischemia (12.7% vs. 31.8%, p = 0.007). At 30 days, a 38% reduction in major adverse cardiac events was observed for the transfer group; however, because of the inability to recruit the necessary sample size, this did not achieve statistical significance (8.4% vs. 13.6%, p = 0.331).nnnCONCLUSIONSnPatients with high-risk AMI at hospitals without a catheterization laboratory may have an improved outcome when transferred for primary PTCA versus on-site thrombolysis; however, this will require further study. The marked delay in the transfer process suggests a role for triaging patients directly to specialized heart-attack centers.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial

BACKGROUNDnCoronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease.nnnMETHODSnIn this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651.nnnFINDINGSnBetween Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 29% for PCI (121 events) and 19% for CABG (81 events), HR 1·48 (95% CI 1·11-1·96), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0066). As-treated estimates were 28% versus 19% (1·55, 1·18-2·04, p=0·0015). Comparing PCI with CABG, 5 year estimates were 12% versus 9% (1·07, 0·67-1·72, p=0·77) for all-cause mortality, 7% versus 2% (2·88, 1·40-5·90, p=0·0040) for non-procedural myocardial infarction, 16% versus 10% (1·50, 1·04-2·17, p=0·032) for any revascularisation, and 5% versus 2% (2·25, 0·93-5·48, p=0·073) for stroke.nnnINTERPRETATIONnThe findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease.nnnFUNDINGnBiosensors, Aarhus University Hospital, and participating sites.

Long-Term Results After Simple Versus Complex Stenting of Coronary Artery Bifurcation Lesions Nordic Bifurcation Study 5-Year Follow-Up Results

OBJECTIVESnThis study sought to report the 5-year follow-up results of the Nordic Bifurcation Study.nnnBACKGROUNDnRandomized clinical trials with short-term follow-up have indicated that coronary bifurcation lesions may be optimally treated using the optional side branch stenting strategy.nnnMETHODSnA total of 413 patients with a coronary bifurcation lesion were randomly assigned to a simple stenting strategy of main vessel (MV) and optional stenting of side branch (SB) or to a complex stenting strategy, namely, stenting of both MV and SB.nnnRESULTSnFive-year clinical follow-up data were available for 404 (98%) patients. The combined safety and efficacy endpoint of cardiac death, non-procedure-related myocardial infarction, and target vessel revascularization were seen in 15.8% in the optional SB stenting group as compared to 21.8% in the MV and SB stenting group (pxa0= 0.15). All-cause death was seen in 5.9% versus 10.4% (pxa0= 0.16) and non-procedure-related myocardial infarction in 4% versus 7.9% (pxa0=xa00.09) in the optional SB stenting group versus the MV and SB stenting group, respectively. The rates of target vessel revascularization were 13.4% versus 18.3% (pxa0= 0.14) and the rates of definite stent thrombosis were 3% versus 1.5% (pxa0= 0.31) in the optional SB stenting group versus the MV and SB stenting group, respectively.nnnCONCLUSIONSnAt 5-year follow-up in the Nordic Bifurcation Study, the clinical outcomes after simple optional side branch stenting remained at least equal to the more complex strategy of planned stenting of both the main vessel and the side branch.

Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation

The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm (SR) in patients with paroxysmal atrial fibrillation (AF). The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF (<48 hours). Seventy-two patients were randomized to receive 30 mg/kg of either amiodarone or placebo. Conversion to SR was verified by 24-hour Holter monitoring. Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring. The remaining study groups were comparable (n = 31 for each), except that in the placebo group beta blockers were more common. The patients receiving amiodarone converted to SR more effectively than those receiving placebo (p<0.0001). At 8 hours, approximately 50% of patients in the amiodarone group and 20% in the placebo group (Holter successful) had converted to SR, whereas after 24 hours the corresponding figures were 87% and 35%, respectively. The median time for conversion (8.7 hours for amiodarone and 7.9 hours for placebo) did not differ in the groups. Amiodarone was hemodynamically well tolerated, and the number of adverse events in the study groups was similar. Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF.

Coronary bifurcation lesions treated with simple or complex stenting: 5-year survival from patient-level pooled analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study

AIMSnRandomized trials of coronary bifurcation stenting have shown better outcomes from a simple (provisional) strategy rather than a complex (planned two-stent) strategy in terms of short-term efficacy and safety. Here, we report the 5-year all-cause mortality based on pooled patient-level data from two large bifurcation coronary stenting trials with similar methodology: the Nordic Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study: old, new, and evolving strategies (BBC ONE).nnnMETHODS AND RESULTSnBoth multicentre randomized trials compared simple (provisional T-stenting) vs. complex (culotte, crush, and T-stenting) techniques, using drug-eluting stents. We analysed all-cause death at 5 years. Data were collected from phone follow-up, hospital records, and national mortality tracking. Follow-up was complete for 890 out of 913 patients (97%). Both Simple and Complex groups were similar in terms of patient and lesion characteristics. Five-year mortality was lower among patients who underwent a simple strategy rather than a complex strategy [17 patients (3.8%) vs. 31 patients (7.0%); P = 0.04].nnnCONCLUSIONnFor coronary bifurcation lesions, a provisional single-stent approach appears to be associated with lower long-term mortality than a systematic dual stenting technique.

CHADS2, CHA2DS2-VASc and HAS-BLED as predictors of outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention

INTRODUCTIONnCHADS2 and CHA2DS2-VASc scores are used to estimate thromboembolic risk in atrial fibrillation (AF). HAS-BLED is recommended for bleeding risk prediction. Their value in predicting the outcome of AF patients after percutaneous coronary intervention (PCI) is unknown. Thus, our aim was to assess whether these simple risk scores are useful in predicting outcome in these patients.nnnMATERIALS AND METHODSnAFCAS is an observational, multicenter, prospective registry including patients (n=929) with AF referred for PCI. Primary study endpoints were 1) all cause mortality; 2) major adverse events (all-cause mortality, myocardial infarction, repeat revascularization, stent thrombosis, transient ischemic attack, stroke or other arterial thromboembolism; MACCE); and 3) bleeding at 12 months follow-up. CHADS2 and CHA2DS2-VASc scores and a modified HAS-BLED (mHAS-BLED) score (omitting labile INR and liver function) were calculated.nnnRESULTSnPatients were distributed as follows: CHADS2 low 29.5%, intermediate 55.2%, high 15.3%; CHA2DS2-VASc low 9.6%, intermediate 46.0%, high 44.5%. A high CHA2DS2-VASc score was predictive of all-cause mortality (p=0.02), whereas CHADS2 was not. High CHA2DS2-VASc score predicted MACCE (HR 2.24, 95%CI 1.21-4.17, p=0.01), as did a high CHADS2 score (HR 1.60, 95%CI 1.05-2.45, p=0.029). Their predictive performance was only modest (C indexes 0.56-0.57). CHADS2 or CHA2DS2-VASc scores were not associated with bleeding. High mHAS-BLED scores (≥3) were not associated with any of the study outcomes.nnnCONCLUSIONSnHigh CHA2DS2-VASc score was the best predictor of thrombotic outcomes after PCI in a high risk AF population. High mHAS-BLED score was not predictive of bleeding events. More accurate, simple risk scores are needed.

Clinical outcome after crush versus culotte stenting of coronary artery bifurcation lesions: the Nordic Stent Technique Study 36-month follow-up results.

OBJECTIVESnThe aim of the study was to compare long-term follow-up results of crush versus culotte stent techniques in coronary bifurcation lesions.nnnBACKGROUNDnThe randomized Nordic Stent Technique Study showed similar 6-month clinical and 8-month angiographic results with the crush and culotte stent techniques of de novo coronary artery bifurcation lesions using sirolimus-eluting stents. Here, we report the 36-month efficacy and safety of the Nordic Stent Technique Study.nnnMETHODSnA total of 424 patients with a bifurcation lesion were randomized to stenting of both main vessel and side branch with the crush or the culotte technique and followed for 36 months. Major adverse cardiac events-the composite of cardiac death, myocardial infarction, stent thrombosis, orxa0target vessel revascularization-were the primary endpoint.nnnRESULTSnFollow-up was complete for all patients. At 36 months, the rates of the primary endpoint were 20.6% versus 16.7% (pxa0= 0.32), index lesion restenosis 11.5% versus 6.5% (pxa0= 0.09), and definitexa0stent thrombosis 1.4% versus 4.7% (pxa0= 0.09) in the crush and the culotte groups, respectively.nnnCONCLUSIONSnAt 36-month follow-up, the clinical outcomes were similar for patients with coronary bifurcation lesions treated with the culotte or the crush stent technique. (Nordic Bifurcation Study. How to Use Drug Eluting Stents [DES] in Bifurcation Lesions? NCT00376571).

Intravascular ultrasound assessed incomplete stent apposition and stent fracture in stent thrombosis after bare metal versus drug-eluting stent treatment the Nordic Intravascular Ultrasound Study (NIVUS).

BACKGROUNDnThis prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial.nnnMETHODSn124 patients with definite ST were assessed by IVUS during the acute ST event. The study was conducted in 15 high-volume percutaneous coronary intervention -centers in the Nordic-Baltic countries.nnnRESULTSnIn early or late ST there were no differences in ISA between DES and BMS. In very late ST, ISA was a more frequent finding in DES than in BMS (52% vs.16%; p=0.005) and the maximum ISA area was larger in DES compared to BMS (1.1 ± 2.3mm(2) vs. 0.1 ± 0.5mm(2); p=0.004). Further, ISA was more prevalent in sirolimus-eluting than in paclitaxel-eluting stents (58% vs. 37%; p=0.02). Stent fractures were found both in DES (16%) and BMS (24%); p=0.28, and not related to time of stent thrombosis occurrence. For stents with nominal diameters ≥ 2.75 mm, 38% of the DES and 22% of the BMS had a minimum stent area of less than 5mm(2); p=0.14.nnnCONCLUSIONSnVery late stent thrombosis was more prevalent and associated with more extensive ISA in DES than in BMS treated patients. Stent fracture was a common finding in ST after DES and BMS implantation.

Changing risk of patients undergoing coronary artery bypass surgery.

The aim of the present study was to evaluate the changing risk of patients undergoing coronary artery bypass grafting (CABG). Residents of Oulu who underwent coronary angiography and/or revascularization from 1993 to 2006 formed the basis of this community-wide study. One thousand three hundred and forty-nine consecutive patients who underwent CABG have been included in the analysis on changing operative risk and results after CABG. A significant increase in the operative risk occurred in patients who underwent CABG (mean logistic EuroSCORE in 1278 patients: 1993-1997: 3.7%; 1998-2002: 4.6%; 2003-2006: 5.4%; P<0.0001). Thirty-day mortality decreased during the last period (1993-1997: 2.5%; 1998-2002: 3.0%; 2003-2006: 1.6%; P=0.49). The area under the ROC curve of logistic EuroSCORE (1993-1997: 0.86; 1998-2002: 0.78; 2003-2006: 0.99) for prediction of 30-day postoperative mortality markedly improved during the last study period. Despite the increased operative risk, off-pump coronary surgery was associated with lower immediate postoperative mortality rates. Contrary to on-pump surgery, immediate postoperative death occurred after off-pump surgery only in patients with additive EuroSCORE >or=6. The results of this study suggest that improved perioperative care as well as changes in operative strategy are positively faced with the increased burden of comorbidities and operative risk of patients currently undergoing CABG.