Impact of advanced age on myocardial perfusion, distal embolization, and mortality patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb–IIIa inhibitors

Despite mechanical reperfusion, the outcome is still unsatisfactory in elderly patients with ST-segment elevation myocardial infarction (STEMI). The vast majority of studies have been conducted without extensive use of glycoprotein (Gp) IIb–IIIa inhibitors, which have been associated with improved perfusion and survival. Thus the aim of the current study was to evaluate the impact of age on the angiographic and clinical outcome patients with STEMI undergoing primary angioplasty with Gp IIb–IIIa inhibitors. Our population is represented by a total of 1,662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials comparing early versus late administration of Gp IIb–IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. A total of 231 (13.9 %) patients were older than 75 years. Elderly patients showed a larger prevalence of female gender, hypertension, and diabetes, more advanced Killip class at presentation and longer time to treatment, but a smaller prevalence of smoking. All patients were treated with GP IIb–IIIa inhibitors. Elderly patients showed a significantly impaired postprocedural thrombolysis in myocardial infarction (TIMI) flow (TIMI 0–2: 17.7 vs 10.3 %, P = 0.002) and myocardial perfusion (myocardial blush grade 0–1: 38.3 vs 26.5 %, P = 0.001), and higher prevalence of distal embolization (19.2 vs 9.8 %, P < 0.001), whereas no difference was observed in terms of ST-segment resolution. At follow-up, elderly patients showed a significantly higher mortality (3.2 vs 11.0 %, hazard ratio (HR) (95 % confidence interval (CI)) = 3.78 (2.31–6.16), P < 0.001), which was confirmed after adjustment for baseline confounding factors (HR (95 % CI) = 5.01 (2.63–9.55), P < 0.0001). This study showed that among patients with STEMI undergoing primary angioplasty, advanced age is an independent predictor of mortality after primary angioplasty. Higher rates of distal embolization and poor myocardial perfusion, in addition to the worse risk profile, contribute toward explaining the impact of aging on mortality.     

Gender-related differences in outcome after ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb–IIIa inhibitors: insights from the EGYPT cooperation

Several studies have found that among patients with ST-elevation myocardial infarction (STEMI) treated by thrombolysis, female sex is associated with a worse outcome. The aim of this study was to investigate sex-related differences in clinical and angiographic findings in patients with STEMI treated with primary angioplasty and Gp IIb–IIIa inhibitors. Our population is represented by 1662 patients undergoing primary angioplasty included in the EGYPT database. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Among 1662 patients, 379 were women (22.8%). Female sex was associated with more advanced age, higher prevalence of diabetes, hypertension, more advanced Killip class, longer ischemia time, less often smokers, with higher prevalence of preprocedural recenalization. No difference was observed in terms of postprocedural TIMI flow, myocardial perfusion and distal embolization. Similar findings were observed in terms of enzymatic infarct size and preprocedural ejection fraction. Female gender was associated with higher mortality (6.4% vs. 3.6%, HR = 1.83 [1.12–3.0], P = 0.015). However, the difference disappeared after correction for baseline confounding factors (HR = 1.01 [0.56–1.83], P = 0.98). This study shows that in patients with STEMI treated by primary angioplasty, female gender is associated with higher mortality rate in comparison with men, and this is mainly due to their higher clinical and angiographic risk profiles. In fact, female sex did not emerge as an independent predictor of mortality.     

Impact of diabetes on long-term outcome in STEMI patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors and BMS or DES

Diabetes has been shown to be associated with worse survival and repeat revascularization (TVR) after primary angioplasty. Drug-eluting stent (DES) may offer benefits in terms of TVR, that may be counterbalanced by an higher risk of stent thrombosis, especially among STEMI patients. Aim of the current study was to evaluate the impact of diabetes on 5-year outcome in patients undergoing primary angioplasty with Glycoprotein IIb–IIIa inhibitors in the era of DES. Our population is represented by STEMI patients undergoing primary angioplasty and stent implantation at a tertiary center with 24-h primary PCI capability within 12 h of symptom onset. All patients received glycoprotein IIb–IIIa inhibitors. No patient was lost to follow up. From 2003 to 2005, 270 STEMI patients were treated with DES (n = 180), or BMS (n = 90). A total of 69 patients had history of diabetes at admission (25.5%). At a follow-up of 1510 ± 406 days, diabetes was associated with a higher rate of death (29.5 vs. 5.1%, P < 0.0001), reinfarction (24.1 vs. 9.1%, P < 0.0001), TVR (19.1 vs. 13.1%, P = 0.052), IST (17.2 vs. 6.8%, P < 0.001) and MACE (51.9 vs. 25.1%, P < 0.001). These results were confirmed in both patients receiving BMS or DES, except for TVR, where no difference was observed between diabetic and non-diabetic patients. This study shows that among STEMI patients undergoing primary angioplasty with Gp IIb–IIIa inhibitors, diabetes is associated with worse long-term mortality, reinfarction, and IST, even with DES implantation, that, however, were able to equalize the outcome in terms of TVR as compared to non diabetic patients.     

Low-molecular-weight heparin compared with unfractionated heparin for patients with non–ST-segment elevation acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors: Results from the CRUSADE initiative

Background: Both heparin and glycoprotein (GP) IIb/IIIa inhibitor therapy and early invasive management strategies are recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the treatment of patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS). However, controversy exists about which form of heparin—unfractionated (UF) or low-molecular-weight (LMW)—is preferable. We sought to compare the efficacy and safety of these treatment strategies in a large contemporary population of patients with NSTE ACS. Methods: Using data from the CRUSADE Initiative, we evaluated LMWH and UFH in high-risk NSTE ACS patients (positive cardiac markers and/or ischemic ST-segment changes) who had received early (< 24 hours) GP IIb/IIIa inhibitor therapy and underwent early invasive management. In-hospital outcomes were compared among treatment groups. Results: From a total of 11,358 patients treated at 407 hospitals in the US from January 2002–June 2003, 6881 (60.6%) received UFH and 4477 (39.4%) received LMWH. Patients treated with UFH were more often admitted to a cardiology inpatient service (73.6% vs. 65.5%, P < 0.0001) and more frequently underwent diagnostic catheterization (91.8% vs. 85.9%, P < 0.0001) and percutaneous coronary intervention (PCI) (69.7% vs. 56.9%, P < 0.0001) than patients treated with LMWH. The point estimate of the adjusted risk of in-hospital death or reinfarction was slightly lower among patients treated with LMWH (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.67–0.99) and the risk of red blood cell transfusion was similar (OR 1.01, 95% CI 0.89–1.15). Among patients who underwent PCI within 48 hours, adjusted rates of death (OR 1.14, 95% CI 0.71–1.85), death or reinfarction (OR 0.93, 0.67–1.31), and transfusion (OR 1.16, 0.89–1.50) were similar. Patients who underwent PCI more than 48 hours into hospitalization had reduced rates of death (OR 0.64, 0.46–0.88), death or reinfarction (OR 0.57, 0.44–0.73), and transfusion (OR 0.66, 0.52–0.84). Conclusions: In routine clinical practice, patients treated with GP IIb/IIIa inhibitors have slightly improved outcomes and similar bleeding risks with LMWH than with UFH. These findings are consistent with current ACC/AHA guidelines but raise important questions about the safety and effectiveness of antithrombotic therapy in real-world clinical practice. Abbreviations abstract Using data from the CRUSADE Initiative, we evaluated low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in high-risk patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS) who received early (<24 hours) glycoprotein (GP) IIb/IIIa inhibitors and early invasive management. In-hospital outcomes were compared among treatment groups. LMWH was associated with slightly improved clinical outcomes and similar rates of transfusion compared with UFH. Our results support the current ACC/AHA guidelines recommendations but raise concerns about the safety and efficacy of UFH in the setting of background use of upstream GP IIb/IIIa inhibitors for patients with NSTE ACS in routine clinical practice. CRUSADE is funded by Millennium Pharmaceuticals, Inc. (Cambridge, Massachusetts) and Schering Corporation (Kenilworth, New Jersey). Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership provides an unrestricted grant in support of the program.     

Bivalirudin versus heparin with or without glycoprotein Ⅱb/Ⅲa inhibitors in?patients with STEMI undergoing primary percutaneous coronary intervention:Pooled patient-level analysis from the

Background In the HORIZONS-AMI(Harmonizing Outcomes with Revasculari Zati ON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention(PCI) for ST-segment elevation myocardial infarction(STEMI) treated with bivalirudin had lower bleeding and mortality rates, but higher acute stent thrombosis rates compared with heparin + a glycoprotein Ⅱb / Ⅲa inhibitor(GPI). Subsequent changes in primary PCI, including the use of potent P2Y12 inhibitors, frequent radial intervention, and pre-hospital medication administration, were incorporated into the EUROMAX(European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned 2,218 patients to bivalirudin versus heparin ± GPI before primary PCI.Objectives The goal of this study was to examine the outcomes of procedural anticoagulation with bivalirudin versus heparin ± GPI for primary PCI, given the evolution in primary PCI.Methods Databases from HORIZONS-AMI and EUROMAX were pooled for patient-level analysis. The Breslow-Day test evaluated heterogeneity between trials.Results A total of 5,800 patients were randomized to bivalirudin(n = 2,889) or heparin ± GPI(n = 2,911). The radial approach was used in 21.3% of patients, prasugrel / ticagrelor was used in 18.1% of patients, and GPI was used in 84.8% of the control group. Bivalirudin compared with heparin ± GPI resulted in reduced 30-day rates of major bleeding(4.2% vs. 7.8%; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to0.66; P 0.0001), thrombocytopenia(1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; P = 0.0002), and cardiac mortality(2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; P = 0.03), with nonsignificantly different rates of reinfarction, ischemia-driven revascularization, stroke, and all-cause mortality. Bivalirudin resulted in increased acute( 24 h) stent thrombosis rates(1.2% vs. 0.2%; RR: 6.04; 95% CI: 2.55 to 14.31;P 0.0001), with nonsignificantly different rates of subacute stent thrombosis. Composite net adverse clinical events were lower with bivalirudin(8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; P 0.0001). There was no significant heterogeneity between the 2 trials for these outcomes, and results were consistent across major subgroups.Conclusions Despite increased acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical outcomes, with significant reductions in major bleeding, thrombocytopenia, and transfusions compared? with heparin ± GPI, results that were consistent with evolution in PCI technique and pharmacotherapy.(Harmonizing Outcomes with Revasculari Zati ON and Stents in Acute Myocardial Infarction [HORIZONS-AMI];NCT00433966)(European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723)(From: Journal of the American College of Cardiology Volume 65, Issue 1, 6-13 January 2015, Pages 27-38)     

Bleeding-avoidance strategies and outcomes in patients ≥80 years of age with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the NCDR CathPCI Registry)

The purpose of our study was to evaluate the use of bleeding-avoidance strategies (BAS) and risk-adjusted bleeding over time in patients ≥80 years of age undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction. We analyzed data from the CathPCI Registry from July 1, 2006 through June 30, 2009. Patients were included if they were ≥80 years old, presented with ST-segment elevation myocardial infarction, and underwent primary PCI. We evaluated trends in use of BAS (direct thrombin inhibitors, vascular closure devices, and radial access) and risk-adjusted bleeding over time. Of 10,469 patients ≥80 years old undergoing primary PCI, 1,002, (9.6%) developed a bleeding complication. Use of direct thrombin inhibitors and vascular closure devices increased over time (12.8% to 24.9% and 29.2% to 32.7%, p <0.01 and <0.05 for trends, respectively). Radial access was extremely uncommon (<1%) and did not change over the course of the study. In multivariable analyses, use of BAS was associated with lower bleeding. However, over the course of the study period, overall risk-adjusted bleeding did not decrease significantly (9.9% to 9.4%, p = 0.14 for trend). In conclusion, patients ≥80 years old undergoing primary PCI are at high risk of bleeding, and despite significant increases in use of BAS, the overall rate of bleeding complications remains high.     

Synergistic effect of peptide inhibitors derived from the extracellular and intracellular domain of αIIb subunit of integrin αIIbβ3 on platelet activation and aggregation

α_IIbβ₃, the major platelet integrin, plays a central role in hemostasis and thrombosis. Upon platelet activation, conformation of α_IIbβ₃ changes and allows fibrinogen binding and, subsequently, platelet aggregation. It was previously shown that a lipid-modified platelet permeable peptide, which corresponds to the intracellular acidic membrane distal sequence ¹⁰⁰⁰LEEDDEEGE¹⁰⁰⁸ of α_IIb (pal-K-LEEDDEEGE or pal-K-1000-1008), inhibits thrombin-induced human platelet aggregation, by inhibiting talin association with the integrin. YMESRADR, a peptide corresponding to the extracellular sequence 313–320 of α_IIb, is also a potent platelet aggregation inhibitor by mimicking the effect of a clasp between the head domains of α_IIb and β₃. The aim of the present study was to investigate the synergistic effect of the intra- and extracellular- peptide inhibitors on platelet aggregation, as well as on the phosphorylation of two signaling proteins, focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). Platelet preincubation with Pal-K-LEEDDEGE followed by YMESRADR showed a synergistic inhibitory activity on platelet aggregation. Platelet incubation with threshold inhibitory concentrations of both peptides provoked almost the total inhibition of aggregation, PAC-1 binding, and fibrinogen binding, but not P-selectin exposure on activated platelets’ surface. Like RGDS peptide, this mixture inhibits FAK phosphorylation whose phosphorylation is well known to be consecutive to the aggregation (postoccupancy events). However, in contrast to RGDS peptide that enhances ERK phosphorylation and activation, the mixture of threshold inhibitory concentrations of Pal-K-LEEDDEEGE and YMESRADR inhibits ERK phosphorylation. We suggest that the use of the intracellular in combination with the extracellular peptide inhibitor, acting with a non-RGD-like mechanism, may provide an alternative way to antagonize integrin α_IIbβ₃ activation.     

Primary angioplasty versus intravenous thrombolysis in acute myocardial infarction: can we define subgroups of patients benefiting most from primary angioplasty? Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction Registry and the Myocardial Infarction Registry

OBJECTIVES: We sought to determine the effectiveness of primary angioplasty compared with thrombolysis in clinical practice. BACKGROUND: In clinical practice, primary angioplasty for the treatment of acute myocardial infarction (AMI) has not yet been proven more effective than intravenous thrombolysis, nor have subgroups of patients been identified who would perhaps benefit from primary angioplasty. METHODS: The pooled data of two AMI registries--the Maximal Individual TheRapy in Acute myocardial infarction (MITRA) study and the Myocardial Infarction Registry (MIR)--were analyzed. A total of 9,906 lytic-eligible patients with AMI, with a pre-hospital delay of < or =12 h, were treated with either primary angioplasty (n = 1,327) or thrombolysis (n = 8,579). RESULTS: Despite differences in the patients' characteristics and concomitant diseases between the two groups, the prevalence of adverse risk factors was balanced. Univariate analysis of hospital mortality showed a more favorable course for patients treated with primary angioplasty: 6.4% versus 11.3% (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.43 to 0.67). This was confirmed by logistic regression analysis (multivariate OR 0.58, 95% CI 0.44 to 0.77). Primary angioplasty was associated with a lower mortality in all subgroups analyzed. We observed a significant correlation between mortality and absolute risk reduction (r = 0.82, p < 0.0001) in the different subgroups: as mortality increased, there was an increase in absolute benefit of primary angioplasty compared with thrombolysis. CONCLUSIONS: These large registry data showed the effect of primary angioplasty to be more favorable than thrombolysis for the treatment of patients with AMI in clinical practice. This effect was not restricted to special subgroups of patients. As mortality increased, the absolute benefit of primary angioplasty also increased.     

Comparison of anti-thrombotic strategies using Bivalirudin,Heparin plus Glycoprotein IIb/IIIa inhibitors and Unfractionated Heparin Monotherapy for patients undergoing percutaneous coronary intervention – A single centre observational study

Aims

The study was planned to compare Anti-thrombotic strategies for patients undergoing PCI in a real world population with an emphasis on occurrence of major bleeding, composite ischemic end points and economic outcomes.

Methods

The present study is a single center, prospective, observational study in consecutive patients undergoing PCI at Fortis Escorts Heart Institute (FEHI) and describes Authors'' experience with three different Anti-Thrombotic Strategies in a real world population. Patients were consecutively enrolled in the study and the choice of Anti-thrombotic strategy was left to individual operator(s) based on their own clinical judgment and patient''s affordability. No specific inclusion/exclusion criteria were specified on the choice of Anti-Thrombotic Strategy.

Results

A total 1453 patients were consecutively enrolled into the study and were followed telephonically after 30 days. 252 patients were treated with Bivalirudin (Angiomax) during PCI (17.3%), 430 (29.6%) patients were treated with Heparin plus GPI & remaining 771 (53.1%) were treated with Heparin monotherapy. Incidence of major bleeding was lowest in patients treated with Bivalirudin (1.59%) when compared to Heparin plus GPI (3.49%) and Heparin monotherapy (5.97%), p = 0.005 Bivalirudin vs. Heparin Monotherapy, and p = 0.145, Bivalirudin vs. Heparin + GPI. No bleeding was observed in STEMI patients treated with Bivalirudin compared to 7.4% in patients treated with GPI and 14.3% in patients treated with UFH. Similarly non-access site bleeding was lowest in patients treated with Bivalirudin. Only 4 patients (1.6%) treated with Bivalirudin required Blood transfusion compared to 25 in Heparin plus GPI (5.8%) and 38 (5%) in Heparin Monotherapy arm. In Composite Ischemic end-points, no “All-cause Mortality” was observed in Bivalirudin group compared to 2.8% in Heparin plus GPI. Early stent thrombosis was seen in 1 patient with Heparin plus GPI and none with Heparin monotherapy and Bivalirudin group. None of the patients underwent TLR (target lesion revascularization) and TVR (target vessel revascularization) within 30 days post procedure other than one early stent thrombosis reported with Heparin plus GPI. Cost of blood product transfusion was lower with Bivalirudin as compared to Heparin plus GP IIb/IIIa arm (p = 0.01) and with Heparin alone (p = 0.001). Due to lower complications including blood transfusions and reduced hospital stay in Bivalirudin group, these benefits outweigh the incremental cost due to higher acquisition cost of the drug.

Conclusion

Bivalirudin use during PCI is associated with a distinct advantage of having lower access site and non-access site bleeding without compromising on the efficacy. We observed a reduction in blood transfusions, hospital stay and mortality for patients treated with Bivalirudin compared with Heparin plus GPI or Heparin Monotherapy. Bivalirudin can be safely adopted into our Institutional protocol for the treatment of high risk PCI such as STEMI, ACS, and Complex elective PCI.     

Influence of clinical and immunological parameters on the health-related quality of life of patients with primary Sjögren's syndrome

OBJECTIVE: To evaluate health-related quality of life (HR-QoL) in patients with primary SS patients using the SF-36 questionnaire and to analyse the association between the main clinical features and the SF-36 scales. METHODS: We studied 110 patients (105 women and 5 men, mean age of 56 years) with primary SS seen consecutively in the outpatient clinic of our Department. We used the population-based reference values for the Spanish version of the SF-36 health survey as control values for a healthy population. RESULTS: Comparison between patients with primary SS and the control population showed lower scores in all SF-36 scales (p < 0.001). Analysis of the SF-36 scales by gender showed a significant correlation between age and the values for physical functioning (p = 0.013) and bodily pain (p = 0.016) scores. No significant differences in SF-36 scores were found when comparing patients according to the presence or absence of sicca features. Women with vaginal dryness had lower scores for social functioning (61.9 vs. 74.4) and general health (37.2 vs. 44.7) than those without, although the differences were not statistically significant (p > 0.05). Patients with extraglandular involvement had lower scores for the vitality scale (40.8 vs. 54.5 p = 0.007), social functioning (67.0 vs. 79.8, p = 0.010), bodily pain (49.5 vs. 62.5, p = 0.018) and general health (38.6 vs. 49.4 p = 0.001) than those without. CONCLUSION: Patients with primary SS had clearly lower HR-QoL scores than the healthy population; with significantly lower scores in all SF-36 scales and in both summary measures. We identified several epidemiological and clinical SS features related to these lower SF-36 scores. Age at protocol correlated with physical functioning and bodily pain. Vaginal dryness was the sicca feature that most affected the HR-QoL of female SS patients, and a poor HR-QoL was also observed in those patients with a systemic expression of the disease, with pulmonary involvement being the extraglandular manifestation that most contributed to a poor HR-QoL. Our results highlight the importance of earlier diagnostic and therapeutic management of patients with primary SS, which, together with a close follow-up, may contribute to a significant improvement in their HR-QoL.     

Target versus sub-target dose of renin–angiotensin system inhibitors on survival in elderly patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis

BACKGROUND The efficiency of the target versus sub-target dose of renin–angiotensin system inhibitors(RASIs) in elderly patients with heart failure(HF) with reduced ejection fraction(HErEF) remains unclear.METHODS PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials(RCTs) and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly p...