Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors - a VALIDATE-SWEDEHEART Substudy.

Background The clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithromboticmedications. Methods and Results The VALIDATE-SWEDEHEART study (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) included 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST-segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out-of-laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05-7.12; P<0.001). Conclusions IPST is a rare but dangerous complication during percutaneous coronary intervention, independently associated with poor prognosis, even in the current era of potent antiplatelet agents. Future treatment studies are needed to reduce the rate of IPST and to improve the poor outcome among these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

Incidence and outcome of myocardial infarction treated with percutaneous coronary intervention during COVID-19 pandemic.

OBJECTIVE: Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19. METHODS: We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019. RESULTS: A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), p<0.001. Results were consistent in all investigated patient subgroups, indicating no change in patient category seeking cardiac care. Kaplan-Meier event rates for 7-day case fatality were 439 (2.3%) compared with 37 (2.9%) (HR: 0.81, 95% CI (0.58 to 1.13), p=0.21). Time to percutaneous coronary intervention (PCI) was shorter during the pandemic and PCI was equally performed, indicating no change in quality of care during the pandemic. CONCLUSION: The COVID-19 pandemic has significantly reduced the incidence of MI referred for invasive treatment strategy. No differences in overall short-term case fatality or quality of care indicators were observed.

Radial versus femoral access in patients with acute coronary syndrome undergoing invasive management: A prespecified subgroup analysis from VALIDATE-SWEDEHEART.

AIMS: In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with acute coronary syndrome undergoing invasive management. We assessed whether the access site had an impact on the primary endpoint of death, myocardial infarction or major bleeding at 180 days and whether it interacted with bivalirudin/unfractionated heparin. METHODS AND RESULTS: A total of 6006 patients with acute coronary syndrome planned for percutaneous coronary intervention were randomised to either bivalirudin or unfractionated heparin. Arterial access was left to the operator discretion. Overall, 90.5% of patients underwent transradial access and 9.5% transfemoral access. Baseline risk was higher in transfemoral access. The unadjusted hazard ratio for the primary outcome was lower with transradial access (hazard ratio 0.53, 95% confidence interval 0.43-0.67, p<0.001) and remained lower after multivariable adjustment (hazard ratio 0.56, 95% confidence interval 0.52-0.84, p<0.001). Transradial access was associated with lower risk of death (hazard ratio 0.41, 95% confidence interval 0.28-0.60, p<0.001) and major bleeding (hazard ratio 0.57, 95% confidence interval 0.44-0.75, p<0.001). There was no interaction between treatment with bivalirudin and access site for the primary endpoint (p=0.976) or major bleeding (p=0.801). CONCLUSIONS: Transradial access was associated with lower risk of death, myocardial infarction or major bleeding at 180 days. Bivalirudin was not associated with less bleeding, irrespective of access site.

Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction.

BACKGROUND: The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use. METHODS: In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days. RESULTS: A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78-1.18, p=0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68-1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58-1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77-1.24, p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30-5.93, p=0.82). CONCLUSION: Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

Percutaneous haemodynamic and renal support in patients presenting with decompensated heart failure: A multi-centre efficacy study using the Reitan Catheter Pump (RCP).

BACKGROUND: Worsening heart failure complicated by congestion, hypotension, and renal dysfunction is difficult to manage, increasingly common and predicts a poor outcome. Novel therapies are required to facilitate diuresis and implementation of disease-modifying interventions in preparation for hospital discharge. Accordingly, we investigated the haemodynamic and renal effects of the Reitan Catheter Pump (RCP) percutaneous support device in patients admitted with decompensated heart failure (DHF). METHODS: This was a prospective observational study of 20 patients admitted with DHF, ejection fraction < 30%, and Cardiac index (CI) < 2.1 L/min/m2 in need of inotropic/mechanical support. RESULTS: Patients underwent RCP support for a mean of 18.3 (±6.3) hours. The RCP increased CI from 1.84 L/min/m2 (±0.27), to 2.41 L/min/m2 (±0.45, p = 0.04), increased urine output (71 mL/h (±65) to 227 ml/h (±179) (p = 0.006) with a concomitant reduction in serum creatinine (188 µmol/L (±87) to 161 µmol/L (±78) (p = 0.0007). There were no clinically significant haemolysis, vascular injury, or thrombo-embolic complications. CONCLUSIONS: For patients admitted with DHF, the RCP improves cardiac index, diuresis and renal function without causing important complications.

Tailored nurse-led cardiac rehabilitation after myocardial infarction results in better risk factor control at one year compared to traditional care: a retrospective observational study.

BACKGROUND: Cardiac rehabilitation improves prognosis after an acute myocardial infarction (AMI), however, the optimal method of implementation is unknown. The aim of the study was to evaluate the effect of individually-tailored, nurse-led cardiac rehabilitation on patient outcomes. METHOD: This single-centre retrospective observational study included 217 patients (62 ± 9 years, 73% men). All patients attended cardiac rehabilitation including at least two follow-up consultations with a nurse. Patients receiving traditional care (n = 105) had a routine cardiologist consultation, while for those receiving tailored care (n = 112) their need for a cardiologist consultation was individually evaluated by the nurses. Regression analysis was used to analyse risk factor control and hospital readmissions at one year. RESULTS: Patients in the tailored group achieved better control of total cholesterol (- 0.1 vs + 0.4 mmol/L change between baseline (time of index event) and 12-14-month follow-up, (p = 0.01), LDL cholesterol (- 0.1 vs + 0.2 mmol/L, p = 0.02) and systolic blood pressure (- 2.1 vs + 4.3 mmHg, p = 0.01). Active smokers, at baseline, were more often smoke-free at one-year in the tailored group [OR 0.32 (0.1-1.0), p = 0.05]. There was a no significant difference in re-admissions during the first year of follow-up. In the tailored group 60% of the patients had a cardiologist consultation compared to 98% in the traditional group (p < 0.001). The number of nurse visits was the same in both groups, while the number of telephone contacts was 38% higher in the tailored group (p = 0.02). CONCLUSION: A tailored, nurse-led cardiac rehabilitation programme can improve risk factor management in post-AMI patients.

Blood lactate is a predictor of short-term mortality in patients with myocardial infarction complicated by heart failure but without cardiogenic shock.

BACKGROUND: Mortality in patients with acute myocardial infarction (AMI) has improved substantially with modern therapy including percutaneous coronary interventions (PCI) but remains high in certain subgroups such as patients presenting with overt cardiogenic shock. However, the risk for AMI in patients presenting acutely with signs of heart failure but without cardiogenic shock is less well described. We aimed to identify risk factors for mortality in AMI patients with heart failure without overt cardiogenic shock. METHODS: Using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we identified patients with operator-registered heart failure (Killip class II-IV), and evaluated predictors of mortality based on clinical factors from review of patient records. RESULTS: A total of 1260 unique patients with acute myocardial infarction underwent PCI in 2014, of which 77 patients (7%) showed signs of heart failure (Killip II-IV) Overall 30-day mortality in patients with Killip class II-IV was 20% (N = 15). In patients classified Killip IV (1%), 30-day mortality was 50% (N = 6). In patients presenting with mild to moderate heart failure (Killlip class II-III), 30-day mortality was 14% (N = 9). In patients with Killip class II-III, lactate ≥2.5 mmol/L was associated with 30-day mortality, whereas systolic blood pressure < 90 mmHg, age, sex and BMI were not. In patients with lactate < 2.5 mmol/L 30-day mortality was 5% (N = 2) whereas mortality was 28% (N = 7) with lactate ≥2.5 mmol/L. This cut-off provided discriminative information on 30-day mortality (area under ROC curve 0.74). CONCLUSIONS: In patients with AMI and signs of mild to moderate heart failure, lactate ≥2.5 mmol/L provides additional prognostic information. Interventions to reduce risk may be targeted to these patients.

Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

BACKGROUND: The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS: In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS: A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). CONCLUSIONS: Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).

Cangrelor in combination with ticagrelor provides consistent and potent P2Y12-inhibition during and after primary percutaneous coronary intervention in real-world patients with ST-segment-elevation myocardial infarction.

Patients pretreated with ticagrelor with less than 1 hour from percutaneous coronary intervention (PCI) or receiving ticagrelor in cath lab were prospectively included and received cangrelor. Cangrelor was infused for 2 hours and platelet function was assessed as P2Y12 reactivity units (PRU) with the VerifyNow P2Y12 function assay before start of infusion, 15 min after the start of infusion, and 30 min after the end of infusion. A total of n = 32 patients with an average age of 68 (±13) years with n = 22 (69%) males were included. The level of P2Y12 inhibition before cangrelor infusion was started was 249 PRU (IQR 221-271). After 15 min of cangrelor infusion the P2Y12 reactivity was markedly decreased to 71 PRU (IQR 52-104, p < 0.001). At 30 min after end of infusion PRU remained within the therapeutic range, 89 PRU (IQR 50-178; p < 0.001 for comparison with preinfusion) with only n = 4 (12.5%) patients with PRU >225. Results were consistent between patients receiving ticagrelor prehospital or in the cath lab and no statistical differences in PRU were noted between the two groups in any of the three measurements. In conclusion, cangrelor in combination with ticagrelor results in consistent and strong P2Y12 inhibition during and after infusion and cangrelor may bridge the gap until oral P2Y12 inhibitors achieve effect in real-world STEMI patients undergoing primary PCI.

Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial).

BACKGROUND: The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs. METHODS/DESIGN: The VALIDATE-SWEDEHEART trial is a multicenter, prospective, randomized, registry-based, controlled, and open-label clinical trial in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing PCI pretreated with ticagrelor, prasugrel, or cangrelor. We hypothesize that bivalirudin is superior to heparin alone in reducing death, myocardial infarction, and major bleeding events at 180 days (primary end point). The trial will enroll 3,000 patients with STEMI and 3,000 patients with non-STEMI undergoing PCI. The trial will use a hybrid registry-based randomized clinical trial design where inclusion, randomization, and baseline data collection are performed using The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. The primary composite end point (death, myocardial infarction, or major bleeding events at 180 days) will be identified through active screening after 7 and 180 days and adjudicated by a blinded central end point committee. Secondary end points and long-term outcomes will be recorded from national registries. CONCLUSION: The VALIDATE-SWEDEHEART trial is founded on a nationwide clinical registry and uses a hybrid registry-based randomized clinical trial (RRCT) design methodology to evaluate efficacy and safety of bivalirudin as compared to heparin alone for acute coronary syndrome, in a large population receiving contemporary recommended therapies including predominantly radial invasive approach and pretreatment with potent P2Y12 inhibitors.

Outcome after percutaneous coronary intervention for different indications: long-term results from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

AIMS: The aim of this study was to evaluate clinical outcome for different indications for PCI in an unselected, nationwide PCI population at short- and long-term follow-up. METHODS AND RESULTS: We evaluated clinical outcome up to six years after PCI in all patients undergoing a PCI procedure for different indications in Sweden between 2006 and 2010. A total of 70,479 patients were treated for stable coronary artery disease (CAD) (21.0%), unstable angina (11.0%), non-ST-elevation myocardial infarction (NSTEMI) (36.6%) and ST-elevation myocardial infarction (STEMI) (31.4%). Mortality was higher in STEMI patients at one year after PCI (9.6%) compared to NSTEMI (4.7%), unstable angina (2.2%) and stable CAD (2.0%). At one year after PCI until the end of follow-up, the adjusted mortality risk (one to six years after PCI) and the risk of myocardial infarction were comparable between NSTEMI and STEMI patients and lower in patients with unstable angina and stable CAD. The adjusted risk of stent thrombosis and heart failure was highest in STEMI patients. CONCLUSIONS: The risk of short-term mortality, heart failure and stent thrombosis is highest for STEMI patients after PCI. Therapies to reduce stent thrombosis and heart failure appear to be most important in decreasing mortality in patients with STEMI or NSTEMI undergoing PCI.

Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome.

INTRODUCTION: Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS). MATERIALS AND METHODS: We identified all ACS patients on DT upon discharge from Helsingborg Hospital and Skåne University Hospital in Malmö and Lund, Sweden, during 2013. Patients on DT were compared with historical controls discharged with TT. Major bleeding was defined in accordance with the HAS-BLED derivation study. Patients were retrospectively followed for three months. RESULTS: In total, 107 DT patients were identified and compared with 159 controls on TT. Mean HAS-BLED bleeding risk score and duration of treatment were similar between the groups (HAS-BLED 2.2+/-0.8 vs 2.2+/-1.0 units, p=NS; duration 2.7+/-0.8 vs 2.5+/-0.9months, p=NS; DT vs TT). The incidence of spontaneous major bleeding was similar between the groups, as was a composite of all thrombotic events, i.e. peripheral embolism, stroke/TIA and acute coronary syndrome (bleeding 8/106 (7.5%) vs 11/157 (7.0%), p=NS; thrombosis 5/106 (4.7%) vs 5/157 (3.2%), p=NS; DT vs TT). CONCLUSIONS: Rates of thrombotic and bleeding events were similar in patients with TT and patients with ticagrelor and warfarin.

A pharmacodynamic comparison of 5 anti-platelet protocols in patients with ST-elevation myocardial infarction undergoing primary PCI.

BACKGROUND: Despite advances in anti-platelet treatments, there still exists an early increase in both ischemic as well as bleeding events following primary PCI in patients with ST-elevation myocardial infarction (STEMI). Platelet inhibition data of different anti-platelet treatments in the acute phase of a myocardial infarction might offer some insight into these problems. The aim of this study was to evaluate the pharmacodynamic profile of 5 different anti-platelet treatments in the acute phase of STEMI in patients undergoing primary PCI. METHODS: A total of 223 STEMI patients undergoing primary PCI were prospectively included. Patients received either pre-hospital clopidogrel only, pre-hospital clopidogrel followed by prasugrel switch in the cath lab, prasugrel treatment only, pre-hospital clopidogrel followed by ticagrelor switch in the cath lab or pre-hospital ticagrelor only. Platelet reactivity was measured serially using vasodilator-stimulated phosphoprotein (VASP). RESULTS: Patients receiving pre-hospital clopidogrel followed by prasugrel switch showed similar platelet inhibition data as patients receiving prasugrel only, with more than 90% being good responders the day after PCI. Average time from prasugrel administration to a VASP value of <50% was 1.5 hours. In patients receiving pre-hospital ticagrelor, 50% were good responders at completion of PCI and average time to a VASP-value of <50% was 2.3 hours. Only 32% of patients receiving clopidogrel only were responders the day after PCI. CONCLUSIONS: Switching from an upstream bolus dose of clopidogrel to prasugrel at the time of PCI, appeared as a safe and feasible option with no tendency for overshoot or attenuation of platelet inhibition. Pre-hospital administration of ticagrelor was associated with a 50% good responder rate at completion of PCI.

Delay from first medical contact to primary PCI and all-cause mortality: a nationwide study of patients with ST-elevation myocardial infarction.

BACKGROUND: Early reperfusion in the setting of an ST-elevation myocardial infarction (STEMI) is of utmost importance. However, the effects of early versus late reperfusion in this patient group undergoing primary percutaneous coronary intervention (PCI) have so far been inconsistent in previous studies. The purpose of this study was to evaluate in a nationwide cohort the effects of delay from first medical contact to PCI (first medical contact [FMC]-to-PCI) and secondarily delay from symptom-to-PCI on clinical outcomes. METHODS AND RESULTS: Using the national Swedish Coronary Angiography and Angioplasty Register (SCAAR) registry, STEMI patients undergoing primary PCI between the years 2003 and 2008 were screened for. A total of 13 790 patients were included in the FMC-to-PCI analysis and 11 489 patients were included in the symptom-to-PCI analyses. Unadjusted as well as multivariable analyses showed an overall significant association between increasing FMC-to-PCI delay and 1-year mortality. A statistically significant increase in mortality was noted at FMC-to-PCI delays exceeding 1 hour in an incremental fashion. FMC-to-PCI delays in excess of 1 hour were also significantly associated with an increase in severe left ventricular dysfunction at discharge. An overall significant association between increasing symptom-to-PCI delays and 1-year mortality was noted. However, when stratified into time delay cohorts, no symptom-to-PCI delay except for the highest time delay showed a statistically significant association with increased mortality. CONCLUSIONS: Delays in FMC-to-PCI were strongly associated with increased mortality already at delays of more than 1 hour, possibly through an increase in severe heart failure. A goal of FMC-to-PCI of less than 1 hour might save patient lives.

Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score.

AIMS: The aim of this study was to evaluate the prevalence of triple antithrombotic therapy (TT) (warfarin, aspirin and clopidogrel) in patients following an acute coronary syndrome (ACS), the bleeding risk compared to double antiplatelet therapy (DAPT) (aspirin and clopidogrel) and evaluate the accuracy of the HAS-BLED risk score in predicting serious bleeding events in TT patients. METHODS AND RESULTS: We retrospectively identified all ACS patients on TT upon discharge from the Coronary Care Unit at Skane University Hospital between 2005 and 2010. TT patients were compared to age- and sex-matched control patients discharged with DAPT. Major bleeding was defined in accordance with the HAS-BLED derivation study. A total of 2,423 patients were screened, of whom 159 (6.6%) were on TT. The mean age was 67.2 (±0.9) years. The most common indication for TT was atrial fibrillation (n=63, 39.6%) followed by apical akinesia (n=60, 37.8%), and the mean duration of TT was 3.7 (±0.3) months. Upon termination of TT, warfarin was discontinued in 82 (52.2%) patients and clopidogrel in 57 (36.3%) patients. The cumulative incidence of spontaneous bleeding events was significantly higher with TT compared to DAPT at one year (10.2% vs. 3.2%; p=0.01). The HAS-BLED score significantly predicted spontaneous bleeding events in TT patients (area under the receiver operating characteristic [ROC] curve 0.67; 95% CI=0.54-0.79; p=0.048). CONCLUSIONS: TT was relatively common following acute coronary syndrome and was associated with a threefold increase in major bleeding compared to DAPT at one year. The HAS-BLED risk score predicted bleeding events with moderate accuracy.

Long-term safety and efficacy of drug-eluting and bare metal stents in saphenous vein grafts.

BACKGROUND: Long-term safety and efficacy data of drug-eluting stents (DESs) in saphenous vein grafts (SVGs) are lacking. This study sought to compare the clinical outcomes of DES versus bare metal stents (BMS) in SVGs. METHODS: We studied all stent implantations in SVGs in Sweden during 74 months between 2005 and 2011 registered in the Swedish Coronary Angiography and Angioplasty Registry. We evaluated outcome in patients who received DES compared with those who received BMS after adjustments for differences in clinical, vessel, and lesion characteristics. RESULTS: Mean follow-up time was 3 years and 4 months. A total of 4,576 stents, implanted at 3,063 procedures, were included in the analysis of which 2,499 stents (54.6 %) were BMS and 2,077 (45.4%) were DES. The outcome analysis was based on 190 stent thromboses, 898 restenoses, and 523 deaths. The incidence of stent thrombosis did not differ between groups. When adjusted for baseline characteristics, including a propensity score for receiving DES, the incidence of restenosis was significantly lower with DES as compared with BMS (risk ratio 0.83, 95% CI 0.70-0.97, P = .019). There was a difference in mortality in the crude analysis between DES and BMS, and after multivariable adjustment, this difference remained statistically significant (risk ratio 0.80, CI 0.65-0.99, P = .038). CONCLUSIONS: The use of DES compared with BMS in SVGs was associated with a significantly lower adjusted incidence of restenosis and death in this large, national, all-encompassing propensity adjusted observational study.

Safety and efficacy of prasugrel compared with clopidogrel in different regions of the world.

BACKGROUND: Among patients with acute coronary syndrome (ACS), demographics, procedural characteristics and adjunctive medications differ globally. We examined whether there were differential effects of prasugrel compared with clopidogrel in the multinational TRITON-TIMI 38 study. METHODS: We divided the enrollment into 5 pre-specified geographic regions. Patients were randomized to prasugrel or clopidogrel without regard to country of enrollment. End points are expressed as Kaplan-Meier failure estimates through 15 months. Heterogeneity was evaluated using Cox proportional hazards model. Additional sensitivity analyses were performed by dividing countries into categories based on the Human Development Index (HDI), which is a composite measure of social and economic development. RESULTS: 13,608 patients were enrolled. Clinical characteristics including age, comorbidities, ACS presentation, stent types, and adjunctive medications differed broadly among regions. Despite these differences, no regional heterogeneity was observed with prasugrel compared to clopidogrel in the reduction of ischemic events (HR range: 0.76-0.87, p(interaction)>0.10 for each) and stent thrombosis (HR range: 0.34-0.72, p(interaction)>0.10 for each) or in the increased rate of non-CABG TIMI major bleeding (HR range: 1.16-1.76, p(interaction)>0.10 for each). There was a consistent trend in net clinical benefit (all cause death/MI/stroke/non-CABG TIMI major bleeding) favoring prasugrel (HR range: 0.81-0.97, p(interaction)>0.10 for each). Consistent results were also observed regarding the safety and efficacy of prasugrel compared with clopidogrel in both developed and developing countries. CONCLUSIONS: Despite differences in patient demographics, procedural techniques and adjunctive medications, consistent reduction in ischemic events and increased bleeding were seen with prasugrel compared with clopidogrel throughout the world.

Effect of upstream clopidogrel treatment in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

AIMS Immediate treatment with a loading dose of clopidogrel at diagnosis of ST-segment elevation myocardial infarction (STEMI) is recommended by ESC/AHA/ACC guidelines in patients eligible for primary percutaneous coronary intervention (PCI). However, the evidence for this practice is scarce. METHODS AND RESULTS All patients who underwent PCI for STEMI in Sweden between 2003 and 2008 were identified from the national Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Patients with concomitant warfarin treatment and patients not having received aspirin upstream were excluded, leaving 13 847 patients for the analysis. Groups were compared for death and myocardial infarction (MI) during 1-year of follow-up using Cox regression models with adjustment for differences in baseline characteristics by propensity score methods. The combined primary endpoint of death or MI during 1-year follow-up occurred in 1325 of 9813 patients with upstream clopidogrel and in 364 out of 4034 patients without upstream treatment. After propensity score adjustment, a significant relative risk reduction (HR 0.82, 95% CI 0.73-0.93) in death/MI at 1 year was observed. The secondary endpoint of total 1-year death was significantly reduced (HR 0.76, 95% CI: 0.64-0.90), while the incidence of 1-year MI did not show any significant reduction (HR 0.90, 95% CI 0.77-1.06). Similar results were observed in multivariate analysis on top of propensity scoring and in sensitivity analyses excluding patients without clopidogrel and aspirin at discharge. CONCLUSION This large observational study suggests that upstream clopidogrel treatment prior to arrival at the catheterization lab is associated with a reduction in the combined risk of death or MI as well as death alone in patients with STEMI treated with primary PCI.

Safety and efficacy of drug-eluting vs. bare metal stents in patients with diabetes mellitus: long-term follow-up in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

AIMS: Patients with diabetes mellitus have more extensive coronary artery disease, more disease progression, and restenosis. The use of drug-eluting stents (DES) in these patients is widespread, despite uncertain long-term safety and efficacy. METHODS AND RESULTS: All consecutive patients with diabetes mellitus in Sweden who underwent percutaneous coronary intervention were entered into the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) during 2003-06 with complete follow-up for 1-4 years (median 2.5). Patients who received at least one DES (n = 4754) were compared with those who received only bare metal stents (BMS) (n = 4956) at the index procedure. Combined outcome of death or myocardial infarction (MI) showed no difference for DES vs. BMS, relative risk (RR), 0.91 [95% confidence interval (CI), 0.77-1.06]. Myocardial infarction was significantly less common with DES in patients who received only one stent RR, 0.80 (95% CI, 0.66-0.96). The restenosis rate was 50% lower in DES-treated patients RR, 0.50 (95% CI, 0.35-0.70) and was associated with a higher adjusted RR of MI, RR, 5.03 (95% CI, 4.25-5.97). DES was associated with reduced restenosis rates in all subgroups of diabetic patients with the greatest benefit in stent diameters <3 mm or stent length >20 mm. The number of lesions treated with DES to prevent one restenosis ranged from 11 to 47 in various subgroups. CONCLUSION: This real-life registry study shows that restenosis was halved by DES in diabetic patients with stable or unstable coronary disease, with similar risk of death or MI up to 4 years compared with BMS.