Paclitaxel-coated versus sirolimus-coated balloon angioplasty for coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: Although use of sirolimus-based analogs has shown superiority over paclitaxel in drug-eluting stents, the relative efficacy of these two agents released from drug-coated balloons (DCB) is unclear. The present meta-analysis is aimed to compare outcomes after percutaneous coronary intervention (PCI) with paclitaxel-coated balloons (PCB) versus sirolimus-coated balloons (SCB) for either in-stent restenosis or native de novo lesions. METHODS: The study outcomes were 1) target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or target lesion revascularization, and 2) follow-up angiographic parameters including late lumen loss (LLL), diameter stenosis, and minimal lumen diameter (MLD). Pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated by using random-effects models. RESULTS: A search of PubMed, EMBASE, and Cochrane Library from their inception to January 2024 identified five randomized clinical trials and three observational studies with a total of 1861 patients (889 in PCB and 972 in SCB groups). During 9-12 months of follow-up, there was no significant difference in TLF (OR 1.01, 95% CI 0.75-1.35) between the two groups. On follow-up angiography at 6-9 months, MLD (WMD 0.10, 95% CI 0.02-0.17) was larger in PCB but there was no statistically significant difference in LLL (WMD -0.11, 95% CI -0.23-0.02) and diameter stenosis (WMD -3.33, 95% CI -8.11-1.45). CONCLUSIONS: Among patients undergoing DCB-only PCI, the risk of TLF was similar during 9-12 months of follow-up after PCB and SCB treatment. However, the MLD was larger favoring PCB over SCB on follow-up angiography.

Mechanical thrombectomy in intermediate- and high-risk acute pulmonary embolism: hemodynamic outcomes at three months.

BACKGROUND: Mechanical thrombectomy has been shown to reduce thrombus burden and pulmonary artery pressure (PAP) and to improve right ventricular (RV) function in patients with high-risk or intermediate-high-risk pulmonary embolism (PE). As hemodynamic data after mechanical thrombectomy for PE are scarce, we aimed to assess the hemodynamic effects of mechanical thrombectomy in acute PE with right heart overload. METHODS: In this prospective, open-label study, patients with acute symptomatic, computed tomography-documented PE with signs of right heart overload underwent mechanical thrombectomy using the FlowTriever System. Right heart catheterization was performed immediately before and after thrombectomy and after three months. Transthoracic echocardiography was performed before thrombectomy, discharge, and at three months. This analysis was done after 20 patients completed three months of follow-up. RESULTS: Twenty-nine patients (34% female) underwent mechanical thrombectomy, of which 20 completed three months follow-up with right heart catheterization. Most patients were at high (17%) or intermediate-high (76%) risk and had bilateral PE (79%). Before thrombectomy, systolic PAP (sPAP) was severely elevated (mean 51.3 ± 11.6 mmHg). Mean sPAP dropped by -15.0 mmHg (95% confidence interval [CI]: -18.9 to -11.0; p < 0.001) immediately after the procedure and continued to decrease from post-thrombectomy to three months (-6.4 mmHg, 95% CI: -10-0 to -2.9; p = 0.002). RV/left ventricular (LV) ratio immediately reduced within two days by -0.37 (95% CI: -0.47 to -0.27; p < 0.001). The proportion of patients with a tricuspid annular plane systolic excursion (TAPSE)/sPAP ratio < 0.31 mm/mmHg decreased from 28% at baseline to 0% before discharge and at three months (p = 0.007). There were no procedure-related major adverse events. CONCLUSIONS: Mechanical thrombectomy for acute PE was safe and immediately reduced PAP and improved right heart function. The reduction in PAP was maintained at three months follow-up.

Long-term efficacy and safety of drug-coated balloons versus drug-eluting stents for small coronary artery disease (BASKET-SMALL 2): 3-year follow-up of a randomised, non-inferiority trial.

BACKGROUND: In the treatment of de-novo coronary small vessel disease, drug-coated balloons (DCBs) are non-inferior to drug-eluting stents (DESs) regarding clinical outcome up to 12 months, but data beyond 1 year is sparse. We aimed to test the long-term efficacy and safety of DCBs regarding clinical endpoints in an all-comer population undergoing percutaneous coronary intervention. METHODS: In this prespecified long-term follow-up of a multicentre, randomised, open-label, non-inferiority trial, patients from 14 clinical sites in Germany, Switzerland, and Austria with de-novo lesions in coronary vessels <3 mm and an indication for percutaneous coronary intervention were randomly assigned 1:1 to DCB or second-generation DES and followed over 3 years for major adverse cardiac events (ie, cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation [TVR]), all-cause death, probable or definite stent thrombosis, and major bleeding (Bleeding Academic Research Consortium bleeding type 3-5). Analyses were performed on the full analysis set according to the modified intention-to-treat principle. Dual antiplatelet therapy was recommended for 1 month after DCB and 6 months after DES with stable symptoms, but 12 months with acute coronary syndromes. The study is registered with ClinicalTrials.gov, NCT01574534 and is ongoing. FINDINGS: Between April 10, 2012, and Feb 1, 2017, of 883 patients assessed, 758 (86%) patients were randomly assigned to the DCB group (n=382) or the DES group (n=376). The Kaplan-Meier estimate of the rate of major adverse cardiac events was 15% in both the DCB and DES groups (hazard ratio [HR] 0·99, 95% CI 0·68-1·45; p=0·95). The two groups were also very similar concerning the single components of adverse cardiac events: cardiac death (Kaplan-Meier estimate 5% vs 4%, HR 1·29, 95% CI 0·63-2·66; p=0·49), non-fatal myocardial infarction (both Kaplan-Meier estimate 6%, HR 0·82, 95% CI 0·45-1·51; p=0·52), and TVR (both Kaplan-Meier estimate 9%, HR 0·95, 95% CI 0·58-1·56; p=0·83). Rates of all-cause death were very similar in DCB versus DES patients (both Kaplan-Meier estimate 8%, HR 1·05, 95% CI 0·62-1·77; p=0·87). Rates of probable or definite stent thrombosis (Kaplan-Meier estimate 1% vs 2%; HR 0·33, 95% CI 0·07-1·64; p=0·18) and major bleeding (Kaplan-Meier estimate 2% vs 4%, HR 0·43, 95% CI 0·17-1·13; p=0·088) were numerically lower in DCB versus DES, however without reaching significance. INTERPRETATION: There is maintained efficacy and safety of DCB versus DES in the treatment of de-novo coronary small vessel disease up to 3 years. FUNDING: Swiss National Science Foundation, Basel Cardiovascular Research Foundation, and B Braun Medical.

Preclinical Evaluation of the Temporary Drug-Coated Spur Stent System in Porcine Peripheral Arteries.

BACKGROUND: Drug penetration into the deeper arterial wall of heavily calcified lesions is one of the limitations of drug-coated balloons and drug-eluting stents in vascular interventions. The Temporary Spur Stent (TSS) system is characterized by a self-expanding nitinol stent that is uniformly covered in radialspikes, which, when coated, should allow a deeper penetration and longer retention of the drug into the diseased artery walls by penetrating through the calcified plaques. MATERIALS AND METHODS AND RESULTS: Uncoated TSS and paclitaxel (PTX)-coated TSS systems have been deployed in porcine peripheral arteries. Four weeks after the deployment of uncoated TSS systems, no adverse vascular remodeling or neointimal formation in the treated vessel segments were noticed. PTX-coated TSS systems transferred 9%±7% of the drug that was on the device to the targeted vessel area (196±163 ng PTX/mg arterial tissue) and the addition of the fluorescent dye Nile red to the coating showed that the spikes promote the transfer of the coating to the deeper layers of the vessel wall. The PTX-coated TSS systems showed a significant reduction in neointimal proliferation compared to the uncoated TSS systems: quantitative angiography showed a vessel diameter stenosis of 37.2%±11.0% and 16.4%±8.8% 4 weeks after the treatment with uncoated and PTX-coated TSS systems, respectively. CONCLUSION: The treatment with the TSS system was well tolerated and the spikesfacilitate the transfer of the coating into deeper layers of the vessel wall. Moreover, the PTX-coated TSS systems effectively inhibit neointimal proliferation.

Valvular heart disease in patients with chronic kidney disease.

Valvular heart disease (VHD) is common in patients with impaired renal function, especially in those with end-stage renal disease (ESRD) undergoing dialysis. Progressive sclerosis and calcification of the valves and valvular annuli are major components of the etiology. These processes typically affect the aortic and mitral valve and can lead to both valvular insufficiency and stenosis. As recommended by the 2017 ESC/EACTS Guidelines for the management of VHD, surgical treatment remains the standard care for most cases of severe VHD. However, chronic kidney disease (CKD) is associated with increased mortality when compared with patients with preserved renal function. Interventional treatment options have emerged as an effective and safe alternative for patients older than 75 years and/or with increased surgical risk. Consequently, in patients with CKD at increased surgical risk who have suitable anatomical morphology, transcatheter replacement and/or repair should be discussed in the interdisciplinary "heart team."

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

BACKGROUND: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. METHODS: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

Novel, vessel anatomy adjusting drug-coated balloon-Preclinical evaluation in peripheral porcine arteries.

BACKGROUND: The diameter of balloons or stents is selected according to the estimated reference vessel diameter and do not adapt to the vessel anatomy. The aim of the present preclinical studies was to investigate a novel, vessel anatomy adjusting hypercompliant drug-coated balloon catheter (HCDCB). METHODS: Hypercompliant balloon membranes were coated in a constricted state with high drug density. Drug adherence was investigated in vitro, transfer to the porcine peripheral arteries and longitudinal distribution in vivo. In young domestic swine, neointimal proliferation was induced by vessel overstretch and continuous irritation by permanent stents. Uncoated hypercompliant balloons (HCB), and standard uncoated balloons and drug-coated balloons (DCB) served as controls. Efficacy was assessed by angiography, optical coherence tomography (OCT), and histomorphometry. RESULTS: HCDCB lost 18.0 ± 3.9% of dose during in vitro simulated delivery to the lesion. Drug transfer to the vessel wall was 13.9 ± 6.4% and drug concentration was 1,044 ± 529 ng/mg tissue. Four weeks after treatment, the histomorphometric neointimal area was smaller with HCDCB versus uncoated HCB (2.39 ± 0.55 mm2 vs. 3.26 ± 0.72 mm2 , p = .038) and area stenosis (OCT) was less (11.6 ± 6.9% vs. 24.7 ± 9.7%, p = .022). No premature death occurred and no in-life clinical symptoms or treatment-associated thrombi were observed. CONCLUSIONS: HCDCB were found to inhibit excessive neointimal proliferation. Balloon adaption to different vessel diameters and shapes may provide drug-delivery in irregular lumen and facilitate balloon selection.

Drug-coated balloons for small coronary artery disease (BASKET-SMALL 2): an open-label randomised non-inferiority trial.

BACKGROUND: Drug-coated balloons (DCB) are a novel therapeutic strategy for small native coronary artery disease. However, their safety and efficacy is poorly defined in comparison with drug-eluting stents (DES). METHODS: BASKET-SMALL 2 was a multicentre, open-label, randomised non-inferiority trial. 758 patients with de-novo lesions (<3 mm in diameter) in coronary vessels and an indication for percutaneous coronary intervention were randomly allocated (1:1) to receive angioplasty with DCB versus implantation of a second-generation DES after successful predilatation via an interactive internet-based response system. Dual antiplatelet therapy was given according to current guidelines. The primary objective was to show non-inferiority of DCB versus DES regarding major adverse cardiac events (MACE; ie, cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation) after 12 months. The non-inferiority margin was an absolute difference of 4% in MACE. This trial is registered with ClinicalTrials.gov, number NCT01574534. FINDINGS: Between April 10, 2012, and February 1, 2017, 382 patients were randomly assigned to the DCB group and 376 to DES group. Non-inferiority of DCB versus DES was shown because the 95% CI of the absolute difference in MACE in the per-protocol population was below the predefined margin (-3·83 to 3·93%, p=0·0217). After 12 months, the proportions of MACE were similar in both groups of the full-analysis population (MACE was 7·5% for the DCB group vs 7·3% for the DES group; hazard ratio [HR] 0·97 [95% CI 0·58-1·64], p=0·9180). There were five (1·3%) cardiac-related deaths in the DES group and 12 (3·1%) in the DCB group (full analysis population). Probable or definite stent thrombosis (three [0·8%] in the DCB group vs four [1·1%] in the DES group; HR 0·73 [0·16-3·26]) and major bleeding (four [1·1%] in the DCB group vs nine [2·4%] in the DES group; HR 0·45 [0·14-1·46]) were the most common adverse events. INTERPRETATION: In small native coronary artery disease, DCB was non-inferior to DES regarding MACE up to 12 months, with similar event rates for both treatment groups. FUNDING: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Basel Cardiovascular Research Foundation, and B Braun Medical AG.

Does renal function affect the efficacy or safety of a pharmacoinvasive strategy in patients with ST-elevation myocardial infarction? A meta-analysis.

BACKGROUND: The efficacy and safety of pharmacoinvasive strategy following fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to renal function have not been established. METHODS: Using patient-level data from 4 randomized controlled trials, we examined the efficacy and safety of pharmacoinvasive versus standard treatment after fibrinolysis for STEMI. Patients were stratified based on the estimated glomerular filtration rate (eGFR) on presentation (<60 mL/min/1.73 m2 vs ≥60 mL/min/1.73 m2). The primary outcome was the composite of death or reinfarction at 30 days. RESULTS: Of 2,029 patients, 457 (23%) had an eGFR<60 mL/min/1.73 m2. Patients with eGFR<60 mL/min/1.73 m2 were older and had higher Thrombolysis in Myocardial Infarction risk scores. Compared with patients with eGFR≥60 mL/min/1.73 m2, patients with renal dysfunction had higher rates of the primary outcome (5.3% vs 11.8%, respectively; P<.001). There was no significant heterogeneity in the treatment effect of pharmacoinvasive strategy on the primary outcome (P heterogeneity=.73) or the rate of death or reinfarction at 1 year (P heterogeneity=.64) in relation to eGFR. Patients with renal dysfunction had higher rates of in-hospital major bleeding compared with patients with eGFR ≥60 mL/min/1.73 m2 (7.7% vs 4.3%, respectively; P=.004); however, there was no difference in bleeding events between treatment arms in the overall cohort or in relation to eGFR (P heterogeneity=.67). CONCLUSIONS: Renal impairment is associated with increased rates of adverse events in STEMI patients treated with fibrinolysis. However, the safety and efficacy of pharmacoinvasive strategy are preserved in patients with renal impairment on presentation.

A novel drug-coated scoring balloon for the treatment of coronary in-stent restenosis: Results from the multi-center randomized controlled PATENT-C first in human trial.

BACKGROUND: Scoring balloons produce excellent acute results in the treatment of in-stent restenosis (ISR), fibro-calcific and bifurcation lesions but have not been shown to affect the restenosis rate. A novel paclitaxel-coated scoring balloon (SB) was developed and tested to overcome this limitation. METHODS AND RESULTS: SB were coated with paclitaxel admixed with a specific excipient. Patients at four clinical sites in Germany and one in Brazil with ISR of coronary bare metal stent (BMS) were randomized 1:1 to treatment with either a drug-coated or uncoated SB. Baseline and 6-month follow-up quantitative coronary angiography was performed by an independent blinded core lab and all patients will be evaluated clinically for up to one year. The primary endpoint was angiographic in-segment late lumen loss (LLL). Secondary endpoints included the rate of clinically driven target lesion revascularization (TLR), composite of major adverse cardiovascular events (MACE), stent thrombosis and other variables. Sixty-one patients were randomized (28 uncoated and 33 drug-coated SB); mean age 65 years, males 72%, and presence of diabetes 39%. At 6-month angiography, in-segment LLL was 0.48 ± 0.51 mm in the uncoated SB group versus 0.17 ± 0.40 mm in the drug-coated SB group (P = 0.01; ITT analysis). The rate of binary restenosis was 41% in the uncoated SB group versus 7% in the drug-coated SB group (P = 0.004). The MACE rate was 32% with the uncoated SB vs. 6% in the drug-coated SB group (P = 0.016). This difference was primarily due to the reduced need for clinically driven TLR in the coated SB group (3% vs. 32% P = 0.004). CONCLUSIONS: A novel paclitaxel-coated coronary SB has been developed and successfully used in a first-in-human randomized controlled trial [ClinicalTrials.gov Identifier: NCT01495533]. © 2015 Wiley Periodicals, Inc.

Results From the International Drug Coated Balloon Registry for the Treatment of Bifurcations. Can a Bifurcation Be Treated Without Stents?

OBJECTIVES: This observational study assessed the 9-month clinical outcomes in patients with coronary bifurcation lesions suitable for drug-coated balloon (DCB) angioplasty. It was the intention to use DCB's without additional stenting (DCB-only strategy) in selected patients for this chosen strategy. Bail-out main branch (MB) and/or side branch (SB) stenting, however, were permissible when flow limiting dissections or excessive recoil occurred. BACKGROUND: A multitude of interventional strategies have been studied to treat bifurcation lesions. With the availability of DCB angioplasty, investigators have been using this interventional tool with the optional implantation of bare metal stents (BMS). METHODS: This study is an international, prospective, multicenter registry enrolling patients with coronary bifurcation lesions including a side branch ≥2 mm in diameter. Patients with stable angina and documented ischemia or selected forms of unstable angina due to a culprit bifurcation lesion of any Medina classification type were recruited. The primary endpoint was clinically driven target-lesion revascularization (TLR) at 9 months. Secondary endpoints included 9-month major adverse cardiac events (death, myocardial infarction, or TLR), technical success, in-hospital outcomes and vessel thrombosis rates. RESULTS: A total 127 patients 66.1 ± 10.1 years of age were enrolled. Demographic characteristics were 80.3% (102/127) male gender, 31.5% (40/127) diabetes, 91.3% (116/127) hypertension, 7.1% (9/127) ST-elevation myocardial infarction (STEMI), and 9.4% (12/127) non ST-elevation myocardial infarction (NSTEMI). The 130 lesions were treated with 184 DCB's and 64 BMS. In 53.8% (70/130) of all lesions the DCB-only strategy could be used while 34.6% (45/130) of lesions had at least 1 stent (BMS) in the main branch, 8.5% (11/130) had at least 1 stent in the side branch and 3.1% (4/130) needed at least 1 stent in the main and side branch. 94.5% patients (121/127) were available for follow-up after 9.8 ± 2.0 months. The TLR rate was 4.6% in the absence of any thrombotic events in the treated vessels whereas the 9-month MACE rate was 6.2%. CONCLUSION: This observational study suggests that the DCB-only strategy is safe and effective to treat selected bifurcations while benefiting from a shortened dual antiplatelet therapy (DAPT).

Evaluation of occurring complications after flow diverter treatment of elastase-induced aneurysm in rabbits using micro-CT and MRI at 9.4 T.

INTRODUCTION: Flow diverters are increasingly being used to treat intracranial aneurysms. This study evaluates occurring complications of flow-diverting devices in the treatment of experimental aneurysms, involving the use of micro-CT and small animal MRI at 9.4 T, in correlation to angiographic and histological findings. METHODS: We previously published two preclinical studies, in which we assessed two different flow diverters in the treatment of elastase-induced aneurysms. Devices have been implanted across the aneurysm neck as well as in the abdominal aorta. From these studies, a total of 65 devices (prototype FD (n = 30) and Derivo embolization device (n = 35)) additionally underwent micro-CT and MRI after angiographic follow-up and before being histologically examined. RESULTS: The different architectures of both devices were precisely comparable due to high-resolution micro-CT imaging. Micro-CT revealed wire fractures in nine cases (30 %) only with the prototype FD. In three cases (10 %), severe wire fractures correlated with an in-stent stenosis due to intimal hyperplasia. Other complications, like distal stent occlusions and post-stent stenosis, were seen in both groups and verified with both imaging techniques. Osseous metaplasia were correlated to calcifications seen with micro-CT. MRI enabled visualization of the position of the implanted devices relative to the aneurysm and revealed incomplete aneurysm neck coverage with the prototype FD in two cases (6.7 %). CONCLUSION: Micro-CT and 9.4-T MRI are valid to discover and understand occurring complications of flow diverters in the preclinical phase and can serve as evaluation tools to minimize complication rates of endovascular devices in the future.

Pulsatile venoarterial perfusion using a novel synchronized cardiac assist device augments coronary artery blood flow during ventricular fibrillation.

Patients with cardiogenic shock have a very high mortality. Here we report the first use of a percutaneous pulsatile cardiac assist device, based on a diagonal pump synchronized with the heart cycle by means of an electrocardiographic signal in adult pigs. Eight domestic pigs underwent mandatory ventilation. During sinus rhythm, there were no differences between pulsatile and nonpulsatile perfusion with regard to pulmonary artery pressure, pulmonary wedge pressure, central venous pressure, mean arterial pressure (MAP), mean pulse pressure, and mean coronary artery flow (CAF). After 2 min of complete cardiac arrest (ventricular fibrillation), circulatory support with the i-cor in venoarterial nonpulsatile extracorporeal membrane oxygenation (ECMO) mode (3 L/min) restored systemic circulation, with an increase of MAP to 78.3 mm Hg and CAF to 5.27 mL/min. After changing from ECMO settings to pulsatile mode (3 L/min, 75 bpm, pulse amplitude range 3500 rpm), MAP did not change significantly (75.6 mm Hg); however, CAF increased to 8.45 mL/min. After changing back to nonpulsatile mode, MAP remained stable (83.6 mm Hg), but CAF decreased to 4.85 mL/min. Thereafter, pulsatile cardiac assist was established with a reduced blood flow of 2.5 L/min, and the pulse amplitude range was extended to 4500 rpm. Under these conditions, MAP remained stable (71.0 mm Hg), but CAF significantly increased to 15.2 mL/min (P < 0.05). Percutaneous cardiac support using a venoarterial cardiac assist device equipped with a novel diagonal pump is able to restore and increase systemic and coronary circulation during ventricular fibrillation. Electrocardiographically triggered synchronized cardiac assist provides an additional increase of coronary artery flow. These promising results are to be confirmed in humans.

Routine invasive management early after fibrinolysis: relationship between baseline risk and treatment effects in a pooled patient-level analysis of 7 randomized controlled trials.

BACKGROUND: The efficacy of a routine invasive strategy early after fibrinolysis in relation to baseline risk status is unclear. We sought to characterize the interaction between patient risk and treatment with routine invasive strategy early after fibrinolysis for ST-segment elevation myocardial infarction. METHODS: We pooled 2,974 patients from 7 randomized trials of fibrinolysis-treated patients with ST-segment elevation myocardial infarction comparing a routine early invasive strategy with a standard approach of percutaneous coronary intervention (PCI) guided by recurrent ischemia or need for rescue. Cox proportional hazards regression was used to examine the interaction between baseline patient risk classified by Thrombolysis in Myocardial Infarction risk score (low/intermediate: ≤ 5 [n = 2,697] vs high: > 5 [n = 277]) and treatment with routine early invasive strategy. RESULTS: Time to PCI after fibrinolysis was longer among patients randomized to standard treatment compared with routine early invasive strategy in the low/intermediate-risk strata (median 11.4 vs 3.5 hours), but was only marginally different between the 2 groups in the high-risk strata (median 4.1 vs 3.5 hours). There was a significant interaction between treatment assignment and risk status for the composite of 30-day death or reinfarction (P = .01). Compared with standard treatment, routine early invasive strategy was associated with lower 30-day death/reinfarction in the low/intermediate-risk stratum (7.5% vs 4.0%, P < .001), but not in the high-risk stratum (14.9% vs 19.6%, P = .45). CONCLUSIONS: Although clearly beneficial among the larger subgroup of patients at low/intermediate risk, the benefit of a routine early invasive strategy was not evident in the smaller subgroup of higher-risk patients in the context of an increased requirement for urgent PCI in the comparative standard treatment arm.