Dimitrios Venetsanos

Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI

Background The instantaneous wave‐free ratio (iFR) is an index used to assess the severity of coronary‐artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events. Methods We conducted a multicenter, randomized, controlled, open‐label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary‐artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization within 12 months after the procedure. Results A primary end‐point event occurred in 68 of 1012 patients (6.7%) in the iFR group and in 61 of 1007 (6.1%) in the FFR group (difference in event rates, 0.7 percentage points; 95% confidence interval [CI], ‐1.5 to 2.8; P=0.007 for noninferiority; hazard ratio, 1.12; 95% CI, 0.79 to 1.58; P=0.53); the upper limit of the 95% confidence interval for the difference in event rates fell within the prespecified noninferiority margin of 3.2 percentage points. The results were similar among major subgroups. The rates of myocardial infarction, target‐lesion revascularization, restenosis, and stent thrombosis did not differ significantly between the two groups. A significantly higher proportion of patients in the FFR group than in the iFR group reported chest discomfort during the procedure. Conclusions Among patients with stable angina or an acute coronary syndrome, an iFR‐guided revascularization strategy was noninferior to an FFR‐guided revascularization strategy with respect to the rate of major adverse cardiac events at 12 months. (Funded by Philips Volcano; iFR SWEDEHEART ClinicalTrials.gov number, NCT02166736.)

Comparison of two drug-eluting balloons: a report from the SCAAR registry.

AIMS Recently, drug-eluting balloons have received a guideline class IIa recommendation in the treatment of in-stent restenosis after bare metal stent implantation. It is not known if different balloons perform equally. Using a large real world registry, restenosis frequency was reported for two drug-eluting balloons. METHODS AND RESULTS From April 2009 until September 2011, 1,129 patients were treated with paclitaxel-eluting balloons in Sweden. Mean follow-up was 328 ± 210 days. Nine hundred and nineteen patients were treated with a balloon using a contrast agent as a drug-carrier and 217 with a balloon without a contrast agent as a drug-carrier. The indications were predominantly de novo (45.4%) or in-stent restenotic (51.8%) lesions. The overall incidence of restenosis at six months was 3.4% with the paclitaxel balloon using a contrast agent as carrier, compared with 12.5% with the paclitaxel-eluting balloon without a carrier (risk ratio: 0.42; 95% confidence interval [CI] [0.26-0.68]). After adjusting for indications, lesion types and procedural factors, the risk ratio was 0.39; 95% CI (0.24-0.65). CONCLUSIONS This observational study from a large real world population shows a major difference between two paclitaxel-eluting balloons. The findings suggest that there are no class effects for drug-eluting balloons and factors other than the drug may be important for the clinical effect.

Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets: The inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAAD-Tica) study, a randomised controlled trial

AIMS To provide pharmacodynamic data of crushed and chewed ticagrelor tablets, in comparison with standard integral tablets. METHODS Ninety nine patients with stable angina were randomly assigned, in a 3:1:1 fashion, to one of the following 180mg ticagrelor loading dose (LD) formulations: A) Integral B) Crushed or C) Chewed tablets. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60min after LD. High residual platelet reactivity (HRPR) was defined as >208 P2Y12 reaction units (PRU). RESULTS There was no significant difference in PRU values at baseline. PRU 20min after LD were 237 (182-295), 112 (53-238) and 84 (29-129) and 60min after LD, 56 (15-150), 51 (18-85) and 9 (7-34) in integral, crushed and chewed ticagrelor LD, respectively (p<0.01 for both). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60min. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20min whereas no difference was observed at 60min. At 20min, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01). CONCLUSION With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared to standard integral tablets. We also show that administration of chewed tablets is feasible and provides faster inhibition than either crushed or integral tablets. CLINICAL TRIAL REGISTRATION European Clinical Trial Database (EudraCT number 2014-002227-96).

Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR

Objectives To validate the performance of the most commonly used formulas for estimation of glomerular filtration rate (GFR) against measured GFR during the index hospitalisation for ST-elevation myocardial infarction (STEMI). Setting Single centre, methodological study. Participants 40 patients with percutaneous coronary intervention-treated STEMI were included between November 2011 and February 2013. Patients on dialysis, cardiogenic shock or known allergy to iodine were excluded. Outcome measures Creatinine and cystatin C were determined at admission and before discharge in 40 patients with STEMI. Clearance of iohexol was measured (mGFR) before discharge. We evaluated and compared the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rG-CystC) with GFR regarding correlation, bias, precision and accuracy (P30). Agreement between eGFR and mGFR to discriminate CKD was assessed by Cohens κ statistics. Results MDRD-IDMS and CKD-EPI demonstrated good performance to estimate GFR (correlation 0.78 vs 0.81%, bias −1.3% vs 1.5%, precision 17.9 vs 17.1 mL/min 1.73 m2 and P30 82.5% vs 82.5% for MDRD-IDMS vs CKD-EPI). CKD was best classified by CKD-EPI (κ 0.83). CG showed the worst performance (correlation 0.73%, bias −1% to 3%, precision 22.5 mL/min 1.73 m2 and P30 75%). The rG-CystC formula had a marked bias of −17.8% and significantly underestimated mGFR (p=0.03). At arrival, CKD-EPI and rG-CystC had almost perfect agreement in CKD classification (κ=0.87), whereas at discharge agreement was substantially lower (κ=0.59) and showed a significant discrepancy in CKD classification (p=0.02). Median cystatin C concentration increased by 19%. Conclusions In acute STEMI, CKD-EPI showed the best CKD-classification ability followed by MDRD-IDMS, whereas CG performed the worst. STEMI altered the performance of the cystatin C equation during the acute phase, suggesting that other factors might be involved in the rise of cystatin C.

Oxygen therapy in ST-elevation myocardial infarction

Aims To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes. Methods and results The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days. Conclusions Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis.

Long-term efficacy of drug coated balloons compared with new generation drug-eluting stents for the treatment of de novo coronary artery lesions

Studies comparing drug coated balloons (DCB) with new generation drug‐eluting stents (nDES) for the treatment of de novo coronary artery lesions are lacking.

No Benefit of Ticagrelor Pretreatment Compared With Treatment During Percutaneous Coronary Intervention in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Background— The effects of ticagrelor pretreatment in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) is debated. This study investigated the effects of ticagrelor pretreatment on clinical outcomes in this patient group. Methods and Results— Patients with ST-segment–elevation myocardial infarction undergoing primary PCI were included from October 2010 to October 2014 in Sweden. Screening was done using the SWEDEHEART register (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies). A total of 7433 patients were included for analysis with 5438 patients receiving ticagrelor pretreatment and 1995 patients with ticagrelor given only in the catheterization laboratory. The primary end point of the study was 30-day event rates of a composite of all-cause mortality, myocardial infarction (MI), and stent thrombosis. Secondary end points were mortality, MI, or stent thrombosis alone and major in-hospital bleeding. Crude event rates showed no difference in 30-day composite end point (6.2% versus 6.5%; P=0.69), mortality (4.5% versus 4.7%; P=0.86), MI (1.6% versus 1.7%; P=0.72), or stent thrombosis (0.5% versus 0.4%; P=0.80) with ticagrelor pretreatment. Three different statistical models were used to correct for baseline differences. No difference in the composite end point, mortality, MI, or stent thrombosis was seen between the 2 groups after statistical adjustment. No increase in in-hospital major bleeding rate was observed with ticagrelor pretreatment. Conclusions— Ticagrelor pretreatment versus ticagrelor given in the catheterization laboratory in patients with ST-segment–elevation myocardial infarction undergoing primary PCI did not improve the composite end point of all-cause mortality or MI or stent thrombosis or its individual components at 30 days.

Pretreatment with ticagrelor may offset additional inhibition of platelet and coagulation activation with bivalirudin compared to heparin during primary percutaneous coronary intervention

BACKGROUND It remains unknown if bivalirudin compared to heparin confers any additional inhibition of platelet and coagulation activation during primary percutaneous coronary intervention (PPCI) after pretreatment with ticagrelor. METHODS In this substudy of VALIDATE-SWEDEHEART trial, 103 patients pretreated with ticagrelor were randomized before PPCI to heparin or bivalirudin. Blood samples were collected before and 1 and 12 h after PPCI. We measured platelet reactivity (PR) using Multiplate, soluble P-selectin, thrombin-antithrombin complexes (TAT) and prothrombin fragments 1 + 2 (F1 + 2) as markers of platelet and coagulation activation. RESULTS The median (IQR) time from ticagrelor administration to randomization was 63 (29) vs 60 (24) minutes, p = 0.28. ADP-induced PR did not significantly differ between groups over time (heparin vs bivalirudin, AUC 73 (62) vs 74 (68), p = 0.74, 32 (42) vs 43 (51), p = 0.38, 15 (15) vs 19 (15), p = 0.29, before, 1 and 12 h after PPCI). Soluble P-selectin did not significantly differ between groups. At 1 h TAT significantly increased with bivalirudin (3.0 (1.3) to 4.3 (4.2) ug/L; p < 0.01), but not with UFH (3.1 (2.1) to 3.5 (1.6) ug/L, p = 0.24). F1 + 2 increased in both groups but the rise was numerically higher with bivalirudin (170 (85) to 213 (126) pmol/L vs 168 (118) to 191 (103) pmol/L). At 12 h, a comparable significant increase in thrombin generation was observed in both groups. CONCLUSION In patients treated with ticagrelor, we found no major differences between bivalirudin and heparin in platelet aggregation or coagulation markers, which is in agreement with the neutral clinical results of the VALIDATE-SWEDEHEART study.

Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A subgroup analysis of the VALIDATE-SWEDEHEART trial

Aims: Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients. Methods: This study was a prespecified analysis of 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) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days. Results: There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60–1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89–1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54–1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94–1.43) in men, p for interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54–1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93–1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women. Conclusion: In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.

Bivalirudin versus heparin with primary percutaneous coronary intervention

Background: Optimal adjunctive therapy in ST‐segment elevation myocardial infarction (STEMI) patients treated with primary PCI (PPCI) remains a matter of debate. Our aim was to compare the efficacy and safety of bivalirudin to unfractionated heparin (UFH), with or without glycoprotein IIb/IIIa inhibitors (GPI) in a large real‐world population, using data from the Swedish national registry, SWEDEHEART. Method: From 2008 to 2014 we identified 23,800 STEMI patients presenting within 12 hours from symptom onset treated with PPCI and UFH ± GPI or bivalirudin±GPI. Primary outcomes included 30‐day all‐cause mortality and major in‐hospital bleeding. Multivariable regression models and propensity score modelling were utilized to study adjusted association between treatment and outcome. Results: Treatment with UFH ± GPI was associated with similar risk of 30‐day mortality compared to bivalirudin±GPI (5.3% vs 5.5%, adjusted HR 0.94; 95% CI 0.82–1.07). The adjusted risk for 1‐year mortality, 30‐day and 1‐year stent thrombosis and re‐infarction did not differ significantly between UFH ± GPI and bivalirudin±GPI. In contrast, treatment with UFH ± GPI was associated with a significant higher risk of major in‐hospital bleeding (adjusted OR 1.62; 95% CI 1.30–2.03). When including GPI use in the multivariable analysis, the difference was attenuated and no longer significant (adjusted OR 1.25; 95% CI 0.92–1.70). Conclusion: Bivalirudin±GPI was associated with significantly lower risk for major inhospital bleeding but no significant difference in 30‐day or one year mortality, stent thrombosis or re‐infarction compared with UFH ± GPI. The bleeding reduction associated with bivalirudin could be explained by the greater GPI use with UFH.