Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.

BACKGROUND: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. METHODS: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. RESULTS: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). CONCLUSIONS: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. CLINICALTRIALS: gov/study/NCT02270242.

Lower revascularization rates after high-speed rotational atherectomy compared to modified balloons in calcified coronary lesions: 5-year outcomes of the randomized PREPARE-CALC trial.

BACKGROUND: In the PREPARE-CALC trial, severely calcified lesion preparation with rotational atherectomy (RA) before biodegradable polymer sirolimus-eluting stent (SES) implantation demonstrated higher procedural success and comparable rates of acute lumen gain and late lumen loss compared to modified balloons (MB) (scoring/cutting). We aimed to analyze the 5-year outcomes of both lesion preparation strategies. METHODS: PREPARE-CALC randomly assigned 200 patients 1:1 to MB or RA, followed by SES implantation. The principal endpoint of the current analysis was target vessel failure (TVF) at 5 years. RESULTS: At 5 years, MB had comparable rates of TVF to RA (19% vs. 21%, HR 1.14, 95% CI 0.60-2.16, p = 0.687). Subgroup analysis showed a lesion length treatment interaction, favoring MB for short lesions and RA for long ones (p for interaction = 0.042). Target lesion revascularization (TLR) was significantly less common with RA (12 vs. 3%, HR 0.28, 95% CI 0.08-0.98, p = 0.048). In a multivariate analysis, RA was independently protective against TLR (adj. HR 0.17, 95% CI 0.04-0.78, p = 0.022), while ostial lesions were associated with higher TLR independent of treatment strategy (adj. HR 11.3, 95% CI 2.98-42.6, p < 0.001). CONCLUSION: In patients with severely calcified coronary lesions, using MB or RA for lesion preparation followed by biodegradable polymer SES implantation was associated with comparable rates of TVF at 5 years. However, a significant reduction of TLR was observed after RA. PREPARE-CALC is the first randomized trial showing potential clinical advantages of RA over MB during long-term follow-up. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifier: NCT02502851.

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.

Incidence of systemic inflammatory response syndrome and patient outcome following transcatheter edge-to-edge mitral valve repair.

OBJECTIVES: Systemic inflammatory response syndrome (SIRS) is a common finding after cardiovascular interventions. Data on the incidence of SIRS and its impact on outcome in patients undergoing transcatheter edge-to-edge mitral valve repair (MV-TEER) for mitral regurgitation (MR) is lacking. METHODS: From January 2013 to December 2020, 373 patients with moderate or severe MR undergoing MV-TEER were included. SIRS was defined as at least two of the following criteria within 48 h after the procedure: leucocyte count > 12.0 or < 4.0 × 109/l, respiratory rate > 20 breaths per minute or PaCO2 ≤ 4.3 kPa/32 mmHg, heart rate > 90 bpm and temperature > 38.0 °C or < 36.0 °C. The primary endpoint was 3-years all-cause mortality. RESULTS: SIRS was observed in 49.6% (185/373) of patients. Patients who developed SIRS presented more frequently with NYHA III/IV at baseline [SIRS: 82.4% (149/185) vs. no SIRS: 79.0% (147/188); p = 0.029]. Patients who developed SIRS spent more days on ICU (p < 0.001) and overall length of stay was longer (p < 0.001). Relevant residual MR, defined as MR ≥ III in-hospital, was present more often in patients who developed SIRS [SIRS: 11.3% (20/177) vs. no SIRS: 3.93% (7/178), p = 0.036]. At 3 years, all-cause mortality in the entire population was 33.5% (125/373) with an increased all-cause mortality in patients with SIRS compared to patients without SIRS (HR 1.49, [CI 95% 1.04, 2.13]; p = 0.0264). In the multivariate analysis development of SIRS (HR 1.479 [CI 95% 1.016, 2.154]; p = 0.041) was identified as predictor for 3-years all-cause mortality. CONCLUSIONS: SIRS is a common finding after MV-TEER occurring in approximately half of patients. SIRS after MV-TEER was associated with a longer in-hospital stay. In addition, we observed an increased 3-years all-cause mortality in patients with SIRS.

Systemic inflammatory response syndrome in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Data on systemic inflammatory response syndrome (SIRS) after transcatheter aortic valve implantation (TAVI) are scarce and limited to small cohorts. We aimed to investigate its incidence and mid-term impact in a large cohort of TAVI patients. METHODS: From January 2018 to December 2020, 717 patients with severe aortic valve stenosis undergoing TAVI were included. SIRS was defined as fulfilling at least two of the following criteria within 48 h from the procedure: leucocyte count >12.0 or <4.0 × 109/l, respiratory rate > 20 breaths per minute or PaCO2 ≤ 4.3 kPa/32 mmHg, heart rate > 90 beats per minute and temperature > 38.0 °C or <36.0 °C. Clinical endpoints were 1-year rehospitalization for chronic heart failure (CHF) and 2-years all-cause mortality. Event rates during follow-up were calculated as Kaplan-Meier estimates. RESULTS: SIRS developed in 56.3 % (404/717) of patients after TAVI. SIRS occurred more frequently in patients with post-dilatation (SIRS 34.7 % (140/404) vs. no SIRS 23.3 % (73/313); p < 0.001) and major vascular complications (SIRS 16.1 % (65/404) vs. no SIRS 8.6 % (27/313); p = 0.004). Further, ICU days were more in patients who developed SIRS (SIRS 1.56 ± 1.50 days vs. no SIRS 1.22 ± 1.02 days; p = 0.001). At 2-years, all-cause mortality in the entire population was 23.9 %. However, there was no difference in CHF at 1-year (5.9 % vs. 4.1 %; log-rank = 0.347) nor in all-cause mortality at 2-years (22.0 % vs. 26.2 %; log-rank = 0.690) between the groups. CONCLUSIONS: SIRS is a common finding after TAVI, which may prolong hospital stay but is without effect on mortality during 2-years follow-up.

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.

Implantation depth of balloon-expandable transcatheter heart valves and risks for permanent pacemaker implantation and midterm adverse events.

BACKGROUND: Permanent pacemaker implantation (PPI) remains a relevant complication after transcatheter aortic valve implantation (TAVI) and its impact on outcome remains controversial. AIMS: This study aimed to analyze the effects of implantation depth on PPI at 30 days and assess its impact on outcome with the balloon-expandable Sapien 3 (S3) prosthesis. METHODS: Between 2014 and 2018, 849 patients without previous pacemaker undergoing transfemoral TAVI with the S3 were included. Prosthesis implantation depth was measured and divided into Quintiles. An ordinal logistic regression was used to assess its association with PPI, while a multivariate logistic regression was performed to identify predictors of PPI. Survival analyses were performed with the Kaplan-Meier method and a multivariable Cox regression was performed to ascertain the impact of PPI on mortality. RESULTS: Overall, incidence of PPI at 30 days was 9.7%. Implantation depth decreased consistently from a median of 6.7 mm [5.55-8.00] in 2014 to 2.7 mm [2.30-3.50] in 2018 (p < 0.001). When considering Quintiles of implantation depth, incidence of PPI was significantly higher in upper Quintiles and risk for PPI was significantly lower for the 1. Quintile compared to the 5. Quintile (OR: 0.34, 95% CI: [0.16-0.73]; p = 0.003). In the adjusted multivariable logistic regression implantation depth persisted ad independent predictor of PPI at 30 days. Patients requiring PPI at 30 days displayed significantly higher mortality at 4 years compared to patients without PPI (49.5% vs. 40.0%; log-rank = 0.022). In a multivariate analysis, increased logistic EuroScore, diabetes mellitus, and history of atrial fibrillation, were independent predictors of all-cause mortality at 2 years. CONCLUSIONS: Higher prosthesis implantation relative to the virtual aortic annulus was significantly associated with reduced risk for PPI at 30 days. Patients with PPI at 30 days exhibited higher mortality during follow-up, however, only logistic EuroScore, diabetes mellitus, and history of atrial fibrillation were identified as independent predictors of mortality at 2 years.

Clinically Driven Revascularization in High-Risk Patients Treated With Ticagrelor Monotherapy After PCI: Insights from the Randomized TWILIGHT Trial.

Repeat coronary revascularization is a common adverse event after successful percutaneous coronary intervention. This analysis aimed to assess the effects of ticagrelor monotherapy on repeat clinically driven revascularization (CDR). In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomly allocated to aspirin or placebo for 1 year. The primary end point of this analysis was CDR within 12 months after randomization. The key secondary end points were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, stroke, or CDR, and net adverse clinical events (NACEs), including the individual components of MACCEs and clinically relevant bleeding. The analysis was performed in the per-protocol population. CDR occurred in 473 of 7,039 patients and was associated with a significantly higher risk of subsequent all-cause death, myocardial infarction, or stroke (adjusted hazard ratios [HRs] 2.92, 95% confidence interval [CI] 1.82 to 4.67). Ticagrelor monotherapy was associated with a similar 12-month risk of CDR (7.1% vs 6.6%; HR 1.09, 95% CI 0.90 to 1.30, p = 0.363) and MACCEs (8.9% vs 8.6%; HR 1.04, 95% CI 0.89 to 1.22, p = 0.619), and a lower risk of NACEs (12.2% vs 14.6%; HR 0.83 95% CI 0.73 to 0.94, p = 0.004) than ticagrelor plus aspirin. In conclusion, among high-risk patients who underwent percutaneous coronary intervention, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a similar risk of CDR and MACCEs and a decrease of NACEs (TWILIGHT: NCT02270242).

Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials.

BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI. METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [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], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding. RESULTS: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up. CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

Coronary No-Reflow after Primary Percutaneous Coronary Intervention-Current Knowledge on Pathophysiology, Diagnosis, Clinical Impact and Therapy.

Coronary no-reflow (CNR) is a frequent phenomenon that develops in patients with ST-segment elevation myocardial infarction (STEMI) following reperfusion therapy. CNR is highly dynamic, develops gradually (over hours) and persists for days to weeks after reperfusion. Microvascular obstruction (MVO) developing as a consequence of myocardial ischemia, distal embolization and reperfusion-related injury is the main pathophysiological mechanism of CNR. The frequency of CNR or MVO after primary PCI differs widely depending on the sensitivity of the tools used for diagnosis and timing of examination. Coronary angiography is readily available and most convenient to diagnose CNR but it is highly conservative and underestimates the true frequency of CNR. Cardiac magnetic resonance (CMR) imaging is the most sensitive method to diagnose MVO and CNR that provides information on the presence, localization and extent of MVO. CMR imaging detects intramyocardial hemorrhage and accurately estimates the infarct size. MVO and CNR markedly negate the benefits of reperfusion therapy and contribute to poor clinical outcomes including adverse remodeling of left ventricle, worsening or new congestive heart failure and reduced survival. Despite extensive research and the use of therapies that target almost all known pathophysiological mechanisms of CNR, no therapy has been found that prevents or reverses CNR and provides consistent clinical benefit in patients with STEMI undergoing reperfusion. Currently, the prevention or alleviation of MVO and CNR remain unmet goals in the therapy of STEMI that continue to be under intense research.

Reticulated Platelets Predict Cardiovascular Death and Adverse Events in Coronary Artery Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The pro-thrombotic immature or reticulated platelets (RPs) are known to be elevated in high-risk patients and in different pathological settings. It has been shown that RPs correlate with an insufficient antiplatelet response to antiplatelet agents. RPs are emerging novel predictors of adverse cardiovascular events in cardiovascular disease. This study, using the totality of existing evidence, evaluated the prognostic role of RPs in patients with coronary artery disease. METHODS: We performed a systematic review and meta-analysis including trials of acute and chronic coronary syndrome reporting clinical outcomes according to RPs levels in the peripheral blood. We compared patients with elevated RPs (RPshigh) to patients without elevated RPs (RPslow). Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were cardiovascular death, myocardial infarction, ischemic stroke, urgent coronary revascularization and bleedings. RESULTS: A total of 7 studies, including 2213 patients, were included. The risk for MACCE was significantly higher in RPshigh compared to RPslow patients (OR 2.67 [1.87; 3.81], I2 = 43.8%). RPshigh were associated with cardiovascular death (OR 2.09 [1.36; 3.22], I2 = 40.4%). No associations for RPshigh were detected with the other singular components of MACCE: myocardial infarction (OR 1.73 [0.89; 3.38] I2 = 60.5%) and stroke (OR 1.72 [0.59; 4.96] I2 = 21%). The risk of bleeding did not differ between groups(OR 0.58 [0.15; 2.22] I2 = 86.1%). CONCLUSION: Elevated RPs are significantly associated with increased risk of cardiovascular events and cardiovascular death.