Incidence and pattern of urgent revascularization in acute coronary syndromes treated with ticagrelor or prasugrel.

BACKGROUND: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization - TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00-1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09-2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77-1.65]; p = 0.546). CONCLUSIONS: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels.

A Ten-Year Follow-Up Study of the Association Between Uric Acid and Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

The association between uric acid (UA) and long-term mortality in patients with coronary artery disease is poorly investigated. We assessed the association between UA and 10-year mortality after percutaneous coronary intervention (PCI) in 3,998 patients who underwent PCI. Patients were categorized in groups according to UA tertiles: tertile 1 (UA <5.80 mg/100 ml, n = 1,347), tertile 2 (UA 5.80 to 7.04 mg/100 ml, n = 1,340), and tertile 3 (UA >7.94 mg/100 ml, n = 1,311). The primary outcome was 10-year all-cause mortality. All-cause deaths occurred in 1,200 patients: 320 deaths (26.5%) in patients with UA in the first tertile, 325 deaths (26.9%) in patients with UA in the second tertile, and 555 deaths (46.0%) in patients with UA in the third tertile (adjusted hazard ratio 1.22, 95% confidence interval 1.17 to 1.27, p <0.001) for 1 mg/100 ml increment in UA level. Cardiac deaths occurred in 748 patients: 194 deaths (16.5%) in patients with UA in the first tertile, 202 deaths (17.0%) in patients with UA in the second tertile, and 352 deaths (29.7%) in patients with UA in the third tertile (adjusted hazard ratio 1.24 [1.17 to 1.32], p <0.001) for 1 mg/100 ml increment in the UA level. The 10-year rates of target lesion revascularization, target vessel revascularization, or nontarget vessel revascularization did not differ significantly according to the UA level. In conclusion, in patients with coronary artery disease treated with PCI, increased UA level was associated with higher 10-year mortality. Increased UA level was not associated with the progression of atherosclerosis in nontreated coronary vessels or progression of intimal hyperplasia in stented lesions requiring intervention.

Aspirin loading and coronary no-reflow after percutaneous coronary intervention in patients with acute myocardial infarction.

BACKGROUND: The association of aspirin loading with the risk of coronary no-reflow (CNR) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has not been investigated. We assessed the association of aspirin loading before PCI with CNR in patients with AMI. MATERIALS AND METHODS: This study included 3100 patients with AMI undergoing PCI. Of them, 2812 patients received aspirin loading (a single oral [or chewed] or intravenous dose of 150-300 mg) and 288 patients did not receive aspirin loading before PCI. The primary endpoint was CNR, defined as Thrombolysis in Myocardial Infarction blood flow grade of <3 after the PCI. RESULTS: CNR occurred in 130 patients: 127 patients in the group with aspirin loading and 3 patients in the group without aspirin loading before PCI (4.5% vs. 1.0%; odds ratio [OR] = 4.50, 95% confidence interval, [1.42-14.21], p = 0.005). After adjustment, the association between aspirin loading and CNR was significant (adjusted OR = 4.49 [1.56-12.92]; p < 0.001). There was no aspirin loading-by-P2Y12 inhibitor (ticagrelor or prasugrel) interaction (pint = 0.465) or aspirin loading-by-chronic aspirin therapy on admission (pint = 0.977) interaction with respect to the occurrence of CNR after PCI. Chronic low-dose aspirin therapy on admission was not independently associated with higher risk of CNR after PCI (adjusted OR = 1.06 [0.65-1.72]; p = 0.824). CONCLUSION: In patients with AMI undergoing PCI, aspirin loading before the PCI procedure at the guideline-recommended doses was associated with higher odds of developing CNR. However, due to the limited number of events, the findings should be considered as hypothesis generating.

Recurrent Revascularization at 10 Years After Percutaneous Treatment of Drug-Eluting Stent Restenosis.

BACKGROUND: Treatment of patients with recurrence of in-stent restenosis (ISR) remains particularly challenging, with data and guideline recommendations for repeat percutaneous coronary intervention being scant. OBJECTIVES: The aim of this study was to investigate the long-term incidence of recurrent revascularization events after percutaneous treatment of drug-eluting stent (DES) ISR. METHODS: In this post hoc analysis, 402 patients (500 lesions) assigned to plain balloon (PB), drug-coated balloon (DCB), or DES treatment in the randomized ISAR-DESIRE 3 (Efficacy Study of Paclitaxel-Eluting Balloon, -Stent vs. Plain Angioplasty for Drug-Eluting Stent Restenosis) trial were followed up over a median of 10.3 years. The primary endpoint was total repeat target lesion revascularization (R-TLR) including all, first and recurrent, events. RESULTS: At the end of follow-up, first R-TLR was required in 204 lesions, 82 in the PB group, 70 in the DCB group, and 52 in the DES group. The total number of R-TLRs was 373: 162 in the PB group, 124 in the DCB group, and 87 in the DES group. During the first year of follow-up, the risk for total R-TLR was reduced by DCB (HR: 0.36; 95% CI: 0.24-0.54) and DES (HR: 0.23; 95% CI: 0.14-0.38) treatment compared with PB treatment. After 1 year, the risk for total R-TLR was nonsignificantly reduced by DCB treatment (HR: 0.77; 95% CI: 0.51-1.16) and significantly reduced by DES treatment (HR: 0.61; 95% CI: 0.39-0.95) compared with PB treatment. Risk in the DCB and DES groups was similar during (HR: 1.54; 95% CI: 0.89-2.69) and after (HR: 1.26; 95% CI: 0.82-1.92) 1 year. CONCLUSIONS: The total number of R-TLRs over 10 years after treatment of patients with DES ISR was high. DCBs and particularly DES were able to reduce the need for both first and recurrent revascularization compared with PB treatment.

In-hospital Outcomes of Rotational Atherectomy in ST-Elevation Myocardial Infarction: Results From the Multicentre ROTA-STEMI Network.

BACKGROUND: Although the use of rotational atherectomy (RA) is off-label in the setting of ST-elevation myocardial infarction (STEMI), it can be the only option in severely calcified culprit lesions to achieve procedural success. We sought to investigate the safety and feasibility of RA during primary percutaneous coronary intervention (PPCI). METHODS: This was a retrospective observational study of patients who underwent RA during PPCI from 12 European centres. The main outcomes were procedural success (defined as successful stent implantation with final thrombolysis in myocardial infarction [TIMI] flow 3 and residual stenosis < 30%) and in-hospital mortality. A comparison of patients presenting with and without shock was performed. RESULTS: In 104 patients with RA during STEMI, the mean age was 72.8 ± 9.1 years, and 35% presented with cardiogenic shock. Bailout RA was performed in 76.9% of cases. Mean burr size was 1.42 ± 0.21 mm. Procedural success was achieved in 86.5% of cases, with no difference between shocked and nonshocked patients (94.4% vs 82.4%; P = 0.13). In-hospital stent thrombosis occurred in 0.96%, perforation in 1.9% and burr entrapment in 2.9% of cases. In spite of equally high procedural success, in-hospital mortality was higher in shocked (50%) compared with nonshocked patients (1.5%; P < 0.0001). CONCLUSIONS: Patients presenting with STEMI requiring RA, represent a high-risk population, frequently presenting with cardiogenic shock. In this analysis of selected patients, RA was performed as a bailout strategy in the majority, and, as such, RA seems to be feasible with a high procedural success rate. In the absence of cardiogenic shock, RA-facilitated PCI seems to be associated with low in-hospital mortality.

Comparison of long-term outcome in patients with in-stent restenosis treated with intravascular lithotripsy or with modified balloon angioplasty.

BACKGROUND: Modified balloon angioplasty (MB) using a cutting-/scoring balloon or intravascular lithotripsy (IVL) is used in patients with in-stent restenosis (ISR). However, IVL is an off-label use in this setting. The aim of this subgroup analysis of an all-comers registry was to compare IVL to MB angioplasty in patients with ISR. METHODS: The subgroup (n = 117) included all patients with an ISR treated by MB or IVL between 2019 and 2021. Primary endpoint was strategy success (< 20% residual stenosis). The secondary endpoint was cardiac death, acute myocardial infarction (AMI) and target lesion failure/revascularization (TVR). Quantitative coronary angiography was performed in all patients. RESULTS: A total of n = 36 patients were treated by IVL and n = 81 patients by MB. No significant differences in baseline characteristics were observed between the groups. The primary endpoint was reached in 99 patients (84.6%). Patients in the IVL group had less residual stenosis (2.8% vs. 21.0%; p = 0.012). Multivariate regression analysis revealed that IVL had a significant positive effect on reaching the primary end point (Estimate 2.857; standard error (SE) 1.166; p = 0.014). During the follow-up period (450 days) there were no significant differences in rates of cardiac death (IVL n = 2 (1.7%) vs. MB n = 3 (2.6%); p = 0.643), AMI (IVL n = 2 (1.7%) vs. MB n = 4 (3.4%); p = 0.999) and TVR (IVL n = 5 (4.3%) vs. MB n = 14 (12%); p = 0.851). CONCLUSION: IVL results in a significantly lower rate of residual stenosis than MB in patients with ISR. During the long-term follow-up, no differences in rates of cardiac death, AMI or TVR were observed.

Coronary no-reflow and adverse events in patients with acute myocardial infarction after percutaneous coronary intervention with current drug-eluting stents and third-generation P2Y12 inhibitors.

BACKGROUND: The frequency and prognostic value of coronary no-reflow (CNR) was investigated in studies that have used an outdated reperfusion therapy in terms of stent technology and antithrombotic drugs. We assessed the association of CNR with adverse outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and newer antithrombotic drugs, ticagrelor or prasugrel. METHODS: This study included 3100 patients with AMI who underwent PCI with current DES and third-generation P2Y12 inhibitors. CNR was defined as Thrombolysis in Myocardial Infarction (TIMI) blood flow grade ≤ 2 at the end of PCI. The primary end point was 1-year incidence of net adverse clinical and cerebral events-a composite end point of death of any cause, myocardial infarction, stroke or major bleeding. RESULTS: CNR was diagnosed in 130 patients (4.2%). The primary end point occurred in 28 patients in the CNR group and 354 patients in the reflow group (cumulative incidence 23.2% and 12.8%; adjusted hazard ratio = 1.53, 95% confidence interval 1.01-2.33; P = 0.049). The 1-year incidences of death or myocardial infarction (14.6% vs. 7.6%; P = 0.003), myocardial infarction (8.8% vs. 3.9%; P = 0.007) and major bleeding (10.9% vs. 5.6%; P = 0.008) were significantly higher in patients with CNR than patients with reflow. The risk of adverse events in patients with CNR was highest within the first 30 days after PCI. CONCLUSION: In patients with AMI undergoing PCI with current DES and third generation P2Y12 receptor inhibitors, CNR was associated with a higher risk of adverse outcomes at 1 year.

Modified balloons to prepare severely calcified coronary lesions before stent implantation: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The performance of modified balloons (namely cutting or scoring balloons) to prepare severely calcified lesions in patients undergoing percutaneous coronary intervention (PCI) remains controversial. We investigated the clinical and imaging outcomes of patients undergoing PCI assigned to modified balloon therapy to prepare severely calcified coronary lesions before stent implantation. METHODS: In this meta-analysis, we aggregated the study-level data from trials enrolling invasively treated patients who were randomly assigned to modified balloon or control therapy to prepare severely calcified lesions before stenting. The primary outcome was major adverse cardiac events (MACE), including death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included the individual components of the primary outcome, coronary perforation and final minimal stent area (MSA) as measured by intracoronary imaging. RESULTS: A total of 648 participants in six trials were allocated to modified balloon therapy (n = 335) or control therapy (semi-compliant, non-compliant, or super high-pressure balloon, n = 313). The median follow-up was 11 months. Overall, MACE occurred in 8.96% of patients assigned to a modified balloon and 12.78% of patients assigned to control therapy [risk ratio = 0.70, 95% confidence interval (CI) 0.35-1.39; P = 0.24]. There was a significant treatment effect-by-modified balloon type interaction for the outcome MACE in patients assigned to cutting balloon compared with control therapy [RR = 0.40 (0.28-0.56), P for interaction (Pint) < 0.001]. Patients treated with a modified balloon compared with control therapy showed neither a significant difference for the other clinical outcomes nor for final MSA [standardized mean difference = 0.67 (- 0.71, 2.06); P = 0.26]. CONCLUSIONS: In patients treated with PCI for severely calcific coronary artery disease a strategy of lesion preparation with a modified balloon before stenting does not improve clinical or imaging outcomes compared with control therapy. The different performance of cutting and scoring balloons warrants further investigation.

Outcomes of endovascular treatment for popliteal artery disease.

Background: Finding the appropriate endovascular revascularization strategy for patients with peripheral artery disease and a popliteal artery lesion remains particulary challenging. Data regarding predictors for a beneficial outcome are scarce. Patients and methods: All endovascular procedures of popliteal artery lesions (n=227) performed in 197 patients between February 2009 and May 2018 at our institution were retrospectively analyzed. Hemodynamically relevant restenosis represented the primary endpoint. Results: The overall technical success rate was 98% and yielded 99% for stenoses (n=145) and 97% for occlusions (n=82). In a median follow-up of 10 months, the overall rate of restenosis was 23%. After 1 and 2 years, the primary patency rates were 76% and 55% and the secondary patency rate was 100%, respectively. The estimated probability of restenosis was significantly higher in stented lesions (stent vs. no stent; 36.0% vs. 19.1%; p=0.030). Multivariate analysis identified stent implantation (hazard ratio: 2.4; overall P=0.010) and diabetes (hazard ratio 2.0; P=0.023) as significant predictors for the development of restenosis. Conclusions: Endovascular therapy for popliteal artery disease was associated with high technical success rates and accompanied with a promising mid-term outcome, particularly in lesions treated with balloon angioplasty alone.

Ten-year outcomes after percutaneous coronary intervention of in-stent restenosis in saphenous vein grafts.

BACKGROUND: Only few data is available for long-term outcomes of patients being treated for in-stent restenosis (ISR) in saphenous vein grafts (SVG). AIMS: Thus, the aim of this observational, retrospective study was to close this lack of evidence. METHODS: Between January 2007 and February 2021 a total of 163 patients with 186 ISR lesions located in SVG were treated at two large-volume centers in Munich, Germany. Endpoints of interest were all-cause mortality, target lesion revascularization (TLR) and target vessel myocardial infarction (TVMI). Furthermore, recurrent ISR were assessed. Outcomes are presented as Kaplan-Meier event rates. RESULTS: Mean age was 72.6 ± 8.6 years, 90.8% were male, 36.8% were diabetics and 42.3% presented an acute coronary syndrome. ISR were treated with DES in 64.0% and with balloon angioplasty (BA) in 36.0%. After 10 years, the rates for all-cause mortality, TVMI and TLR were 58.2%, 15.4%, and 22.6%, respectively. No statistically relevant differences were found between the types of treatment (DES or BA) regarding all-cause mortality (55.7% vs. 63.2%, p = 0.181), TVMI (13.8% vs. 18.6%, p = 0.215) and TLR (21.8% vs. 25.0%, p = 0.764). Median time between first and recurrent ISR was 270.8 days. Recurrent ISR were treated with DES in a comparable proportion as during first ISR (p = 0.075). Independent predictor of TLR is patient age (p = 0.034). The median follow-up duration was 5.1 years (75% CI 2.8; 8.5). CONCLUSIONS: Clinical event rates after intervention of ISR located in SVG are high without statistically relevant differences regarding the type of treatment. However, further studies are needed.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Very long-term outlook of acute coronary syndromes after percutaneous coronary intervention with implantation of polymer-free versus durable-polymer new-generation drug-eluting stents.

BACKGROUND: Detailed long-term follow-up data on patients with acute coronary syndromes (ACS) in general, and those with ST-elevation myocardial infarction (STEMI) in particular, are limited. We aimed to appraise the long-term outlook of patients undergoing percutaneous coronary intervention (PCI) with state-of-the-art coronary stents for STEMI, other types of ACS and stable coronary artery disease (CAD), and also explore the potential beneficial impact of new-generation polymer-free drug-eluting stents (DES) in this setting. METHODS: Baseline, procedural and very long-term outcome data on patients undergoing PCI and randomized to implantation of new-generation polymer-free vs. durable polymer DES were systematically collected, explicitly distinguishing subjects with admission diagnosis of STEMI, non-ST-elevation ACS (NSTEACS), and stable CAD. Outcomes of interest included death, myocardial infarction, revascularization (i.e. patient-oriented composite endpoints [POCE]), major adverse cardiac events (MACE), and device-oriented composite endpoints (DOCE). RESULTS: A total of 3002 patients were included, 1770 (59.0%) with stable CAD, 921 (30.7%) with NSTEACS, and 311 (10.4%) with STEMI. At long-term follow-up (7.5±3.1 years), all clinical events were significantly more common in the NSTEACS group and, to a lesser extent, in the stable CAD group (e.g. POCE occurred in, respectively, 637 [44.7%] vs. 964 [37.9%] vs. 133 [31.5%], P<0.001). While these differences were largely attributable to adverse coexisting features in patients with NSTEACS (e.g. advanced age, insulin-dependent diabetes, and extent of CAD), the unfavorable outlook of patients presenting with NSTEACS persisted even after multivariable adjustment including several prognostically relevant factors (hazard ratio [HR] of NSTEACS vs. stable CAD 1.19 [95% confidence interval 1.03-1.38], P=0.016). Notably, even after encompassing all prognostically impactful features, no difference between polymer-free and permanent polymer drug-eluting stents appeared (HR=0.96 [0.84-1.10], P=0.560). CONCLUSIONS: Unstable coronary artery disease, especially when presenting without ST-elevation, represents an informative marker of adverse long-term prognosis in current state-of-the-art invasive cardiology practice. Even considering admission diagnosis, and despite of using no polymer, polymer-free DES showed similar results with regards to safety and efficacy when compared with DES with permanent polymer.

Comparison of long-term outcome in patients with calcified stenosis treated with intravascular lithotripsy or with modified balloon angioplasty: a propensity score-adjusted study.

Background: The aim of this two-center, all-comers registry was to compare the effectiveness and safety of intravascular lithotripsy (IVL) to that of modified balloon angioplasty (MB). MB angioplasty using a cutting or scoring balloon is commonly used in patients with calcified coronary arteries. IVL is a new technology for lesion preparation. This is the first study to compare MB with IVL. Methods: The cohort included all patients treated by MB angioplasty or IVL between 2019 and 2021. The primary endpoint was strategy success (<20% residual stenosis). The secondary endpoint was long-term safety outcomes [cardiac death, acute myocardial infarction (AMI), target lesion failure/revascularization (TVR)]. Quantitative coronary angiography (QCA) was performed in all patients. Primary and secondary endpoints were compared using inverse probability of treatment weighting (IPTW) for treatment effect estimation. Results: A total of n = 86 patients were treated by IVL and n = 92 patients by MB angioplasty. The primary endpoint was reached in 152 patients (85.4%). Patients in the IVL group had less residual stenosis (5.8% vs. 22.8%; p = 0.001) in QCA. Weighted multivariable regression analysis revealed that IVL had a significant positive effect on reaching the primary endpoint of strategy success [odds ratio (OR) 24.58; 95% confidence interval (95% CI) 7.40-101.86; p = 0.001]. In addition, severe calcification was shown to result in a lower probability of achieving the primary endpoint (OR 0.08; 95% CI 0.02-0.24; p = 0.001). During the follow-up period (450 days) there was no difference in cardiovascular mortality rate [IVL (n = 5) 2.8% vs. MB (n = 3) 1.7%; p = 0.129]. Patients with unstable angina at the time of the index procedure had the highest probability of cardiovascular death [hazard ratio (HR) 7.136; 95% CI 1.248-40.802; p = 0.027]. No differences were found in long-term rates of AMI (IVL 1.7% vs. MB 2.8%; p = 0.399; IVL HR 2.73; 95% CI 0.4-17.0; p = 0.281) or TVR (IVL 5.6% vs. MB 9%; p = 0.186; IVL HR 0.78; 95% CI 0.277-2.166; p = 0.626). Conclusion: IVL leads to a significantly better angiographic intervention outcome compared to MB angioplasty in our cohort. During long-term follow-up, no differences in cardiovascular mortality, rate of acute myocardial infarction, or target lesion failure/revascularization were observed.

Use of big data from health insurance for assessment of cardiovascular outcomes.

Outcome research that supports guideline recommendations for primary and secondary preventions largely depends on the data obtained from clinical trials or selected hospital populations. The exponentially growing amount of real-world medical data could enable fundamental improvements in cardiovascular disease (CVD) prediction, prevention, and care. In this review we summarize how data from health insurance claims (HIC) may improve our understanding of current health provision and identify challenges of patient care by implementing the perspective of patients (providing data and contributing to society), physicians (identifying at-risk patients, optimizing diagnosis and therapy), health insurers (preventive education and economic aspects), and policy makers (data-driven legislation). HIC data has the potential to inform relevant aspects of the healthcare systems. Although HIC data inherit limitations, large sample sizes and long-term follow-up provides enormous predictive power. Herein, we highlight the benefits and limitations of HIC data and provide examples from the cardiovascular field, i.e. how HIC data is supporting healthcare, focusing on the demographical and epidemiological differences, pharmacotherapy, healthcare utilization, cost-effectiveness and outcomes of different treatments. As an outlook we discuss the potential of using HIC-based big data and modern artificial intelligence (AI) algorithms to guide patient education and care, which could lead to the development of a learning healthcare system and support a medically relevant legislation in the future.

Association of De Ritis Ratio with Prognosis in Patients with Coronary Artery Disease and Aminotransferase Activity within and outside the Healthy Values of Reference Range.

BACKGROUND: The aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (De Ritis ratio), obtained from AST and ALT activities in the healthy range, has not been studied in association with mortality. METHODS: This study included 3392 patients with stable coronary heart disease and aminotransferase activity in the reference range. Patients are categorized into two groups: a group with AST and ALT activity in the healthy range (n = 1697), and a group with AST and/or ALT activity outside the healthy range but in the reference range (n = 1695). The primary endpoint was all-cause mortality at three years. RESULTS: The De Ritis ratio (median 5th-95th percentile] was 0.94 [0.61-1.41] in patients with AST and ALT in the healthy range and 0.93 [0.45-1.96] in patients with AST and/or ALT outside the healthy range (p = 0.700). At three years, there were 86 deaths in patients with AST and ALT in the healthy range: 27 deaths (3.9%) in patients with a De Ritis ratio ≤median, and 59 deaths (8.2%) in patients with the De Ritis ratio >median (adjusted hazard ratio [HR] = 1.16, 95% confidence interval [CI] 0.94 to 1.42; p = 0.159); in patients with AST and/or ALT outside the healthy range, there were 148 deaths: 49 deaths (6.6%) in patients with a De Ritis ratio ≤median, and 99 deaths (14.1%) in patients with De Ritis ratio >median (adjusted HR = 1.27 [1.09-1.48], p = 0.002), with both HRs calculated per unit higher values of the De Ritis ratio. CONCLUSIONS: The De Ritis ratio obtained from AST and ALT activity in the healthy range was not independently associated with higher risk of mortality. The De Ritis ratio obtained from aminotransferase activity outside the healthy range (but still in the reference range) was independently associated with the risk of mortality.

Machine Learning Identifies New Predictors on Restenosis Risk after Coronary Artery Stenting in 10,004 Patients with Surveillance Angiography.

OBJECTIVE: Machine learning (ML) approaches have the potential to uncover regular patterns in multi-layered data. Here we applied self-organizing maps (SOMs) to detect such patterns with the aim to better predict in-stent restenosis (ISR) at surveillance angiography 6 to 8 months after percutaneous coronary intervention with stenting. METHODS: In prospectively collected data from 10,004 patients receiving percutaneous coronary intervention (PCI) for 15,004 lesions, we applied SOMs to predict ISR angiographically 6-8 months after index procedure. SOM findings were compared with results of conventional uni- and multivariate analyses. The predictive value of both approaches was assessed after random splitting of patients into training and test sets (50:50). RESULTS: Conventional multivariate analyses revealed 10, mostly known, predictors for restenosis after coronary stenting: balloon-to-vessel ratio, complex lesion morphology, diabetes mellitus, left main stenting, stent type (bare metal vs. first vs. second generation drug eluting stent), stent length, stenosis severity, vessel size reduction, and prior bypass surgery. The SOM approach identified all these and nine further predictors, including chronic vessel occlusion, lesion length, and prior PCI. Moreover, the SOM-based model performed well in predicting ISR (AUC under ROC: 0.728); however, there was no meaningful advantage in predicting ISR at surveillance angiography in comparison with the conventional multivariable model (0.726, p = 0.3). CONCLUSIONS: The agnostic SOM-based approach identified-without clinical knowledge-even more contributors to restenosis risk. In fact, SOMs applied to a large prospectively sampled cohort identified several novel predictors of restenosis after PCI. However, as compared with established covariates, ML technologies did not improve identification of patients at high risk for restenosis after PCI in a clinically relevant fashion.

Sex Differences in 10-Year Outcomes After Percutaneous Coronary Intervention With Drug-Eluting Stents: Insights From the DECADE Cooperation.

BACKGROUND: Although some studies have investigated sex-related outcomes up to 5 years after percutaneous coronary intervention (PCI), analyses at longer follow-up (ie, to 10 years) in large cohorts treated exclusively with drug-eluting stent (DES) platforms are lacking. Therefore, this study aimed to define whether sex-related differences in long-term outcomes after PCI persist both in the DES era and at longer-term follow-up. METHODS: Individual data of patients treated with DES in 5 randomized controlled trials with 10-year follow-up were pooled. Patients were divided into 2 groups by sex. The analysis of individual participant data was performed using a 1-stage approach by entering a clustering effect by parent study in all univariable and multivariable models focusing on sex. The main outcomes of interest for this analysis included cardiovascular death, myocardial infarction, repeat revascularization, and definite stent thrombosis to 10 years after PCI. Survival was analyzed by the Kaplan-Meier method to estimate the time to first event, and differences between the 2 groups were tested with the log-rank test. Hazard ratios (HRs) and 95% CIs were calculated with a Cox proportional hazards model. Conventional multivariable analyses with adjustment for relevant variables were performed. RESULTS: Among 9700 patients undergoing PCI with DES implantation included in the present analysis, 2296 were women and 7404 were men. Through to 10 years, cardiovascular death occurred in 407 of the 2296 female patients and 1012 of the 7404 male patients (adjusted HR [HRadj], 0.94 [95% CI, 0.80-1.11]). Female sex was associated with a lower risk of repeat revascularization of the target lesion (HRadj, 0.80 [95% CI, 0.74-0.87]), target vessel (HRadj, 0.81 [95% CI, 0.76-0.87]), and nontarget vessels (HRadj, 0.69 [95% CI, 0.62-0.77]). Compared with male patients, female patients displayed an increased risk of myocardial infarction in the first 30 days after PCI with DES (HRadj, 1.65 [95% CI, 1.24-2.19]) but a comparable risk of myocardial infarction thereafter. The risk of definite stent thrombosis was not significantly different between female and male patients (HRadj, 1.14 [95% CI, 0.89-1.47]). CONCLUSIONS: Through to 10-year follow-up after PCI with DES, female patients are at increased risk of early myocardial infarction, receive fewer repeat revascularizations, and have no difference in cardiovascular mortality compared with male patients.

Derivation and validation of the ISAR score to predict the risk of repeat percutaneous coronary intervention for recurrent drug-eluting stent restenosis.

BACKGROUND: The treatment of drug-eluting stent (DES) in-stent restenosis (ISR) is challenging as it has a high risk of recurrence. AIMS: The aim of this analysis was to develop and validate a model to predict the risk of repeat percutaneous coronary intervention (PCI) for recurrent DES-ISR. METHODS: A retrospective, observational analysis was performed including consecutive patients treated with PCI for DES-ISR at two centres in Germany. Included patients were randomly divided into training and validation cohorts. Two regression analyses identified factors associated with repeat PCI for recurrent DES-ISR up to 1 year. The discriminative ability of the resultant model was then compared to a benchmark ISR classification model using bootstrap resampling. A classification and regression tree analysis and a numerical scoring system (the ISAR score) were used to predict the risk of repeat PCI for recurrent DES-ISR based on the identified predictors. RESULTS: We included 1,986 patients in the current analysis, divided randomly into training (1,471 patients, 1,778 lesions) and validation (515 patients, 614 lesions) cohorts. Four factor variables (a non-focal ISR pattern, a time interval to ISR of <6 months, ISR of the left circumflex artery and ISR in a calcified vessel) were associated with repeat PCI for recurrent DES-ISR at 1-year follow-up. On bootstrap resampling analysis, the C-statistic for the model including these four variables was 0.60 (95% confidence interval [CI]: 0.57-0.63), whereas the C-statistic for the benchmark ISR classification model was 0.54 (95% CI: 0.52-0.57), a difference that was statistically significant (delta C-statistic 0.062; 95% CI: 0.035-0.094; p<0.001). The cumulative incidence of repeat PCI for recurrent DES-ISR was over three times higher in DES-ISR lesions with an ISAR score of ≥3 in comparison to lesions with an ISAR score of 0. CONCLUSIONS: This study developed and validated a risk prediction model for repeat PCI for recurrent DES-ISR at 1-year follow-up. This model served to generate the ISAR score, a standardised tool that can be used to predict the 1-year risk of repeat PCI for recurrent DES-ISR.