Platelet glycoprotein IIb/IIIa inhibitors for acute coronary syndromes: initiate treatment early or wait for the catheterization laboratory?

Treatment of patients with acute coronary syndromes (ACS) incorporates several approaches to reverse or mitigate the thrombus, which invariably is at the center of the pathophysiologic process of ACS. Pharmacologic and mechanical strategies are designed to prevent death, reduce myocardial necrosis, and stabilize the plaque to prevent later sequelae. Conventional antithrombotic therapy includes antiplatelet and anticoagulant drugs. Medications that inhibit the platelet glycoprotein IIb/IIIa receptor have been shown to be especially efficacious in the treatment of ACS. Recent clinical trials have validated a strategy of aggressive revascularization, particularly catheter-based percutaneous procedures. This review summarizes new trial results and provides a working algorithm for care of the patient with ACS.     

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.     

Is there a gender paradox in the early invasive strategy for non ST-segment elevation acute coronary syndromes?

This editorial refers to "Do men benefit more than women from aninterventional strategy in patients with unstable angina or non-ST-elevationmyocardial infarction? The impact of gender in the RITA 3 trial".by T.C. Clayton on page 1641 Coronary artery disease and, in particular, acute coronary syndromes(ACS), is the leading cause of mortality and morbidity in industrialisednations.¹ While major advances in the diagnosis and treatmentof ACS, both in terms of pharmacotherapy and catheter-basedrevascularisation, have resulted in a continuing, steady decreasein coronary heart disease (CHD) mortality over the last decadeamong men, the cardiovascular event rate among women has eitherlevelled off or increased – especially in older age groupsand among various ethnic minorities.^2–4 One of these advances, percutaneous coronary intervention (PCI),has become a standard treatment option for many patients –both men and women – with     

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.     

In-hospital outcome of elderly patients with acute coronary syndromes treated with platelet glycoprotein Ⅱb/Ⅲa blockers

Background and objective The safety of intravenous glycoproteinⅡb/Ⅲa inhibitors (GPI) in elderly patients admitted with acute coronary syndrome (ACS) has not yet been established. The purpose of this study was to evaluate the safety of GPI in elderly patients with ACS. Methods Ninety consecutive patients≥70 years of age admitted to a county hospital between 1999-2004 were included. All patients had typical ACS symptoms along with high-risk markers. Results There was no difference in the TIMI risk score between patients who received GPI (n=47) and those who did not (n=43). Patients who received GPI had a lower creatinine clearance (40 cc/min vs. 47cc/min, p= 0.04). Patients who received GPI had a lower incidence of death, reinfarction or major bleeding (19% vs. 4%, p=0.03). There was no significant difference in major bleeding between the 2 groups. None of the patients in either group developed thrombocytopenia. Conclusion This retrospective small study suggests that the use of GPI in a selected group of elderly patients with acute coronary syndrome may be safe. (J Geriatr Cardiol 2005; 2(4):203-205 )     

Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin?

This article will review the results of recent clinical trials evaluating low molecular weight heparins (LMWHs) in the management of patients with acute coronary syndromes of unstable angina and non-ST segment elevation MI. Low molecular weight heparins are a new class of anticoagulants that have a number of advantages over unfractionated heparin (UFH) leading to their increasing use for thrombotic vascular disorders. There is convincing evidence that LMWH is more effective than placebo and at least as effective as UFH in reducing the hard end points of death and recurrent myocardial infarction. Convincing evidence for a superior efficacy is mostly limited to the least robust but most prevalent end point of recurrent angina, and benefits appear to be confined predominantly to high-risk patients. The benefits are sustained long-term, but there appears to be no incremental benefit with prolonged treatment. The risk for major bleeding is approximately equivalent to UFH, but minor hemorrhage is clearly increased, especially with vascular instrumentation. The increased bleeding risk together with its long half-life and absence of specific antidote warrants exercising caution when using LMWH with coronary intervention. Low molecular weight heparins have the potential of being cost-neutral or even cost-saving by reducing resource utilization, especially in the setting of aggressive interventional practice pattern. Last, the issue of whether one LMWH preparation is more effective and cost-effective than others remains an open question that can be answered only by direct head-to-head comparison of different LMWH preparations in randomized trials. In conclusion, subcutaneous weight-adjusted LMWH is as effective and safe as intravenous UFH in the management of patients with acute coronary syndromes. The logistic ease of administration without the need for monitoring anticoagulation appears to be the major advantage over UFH.     

Age,treatment, and outcomes in high-risk non‐ST-segment elevation acute coronary syndrome patients: Insights from the EARLY ACS trial

Background

Elderly patients with acute coronary syndromes (ACS) are at high risk for death and recurrent thrombotic events. We evaluated the efficacy and safety of intensive treatment with glycoprotein IIb/IIIa inhibitors in an elderly population, and the relationships between age, timing of administration, and clinical outcomes.

Methods

We used data from high-risk non–ST-segment elevation ACS patients randomized to early eptifibatide vs. delayed provisional use at percutaneous coronary intervention. In multivariable models, we included age × treatment interaction terms to assess whether treatment effect varied by age after adjusting for confounders.

Results

Of 9406 patients, 13.9% were aged < 55 years; 27.6%, 55–64 years; 33.2%, 65–74 years; and 25.3%, ≥ 75 years. For each 10-year age increase, the adjusted odds ratio (OR) (95% confidence interval [CI]) for 96-hour death, myocardial infarction (MI), recurrent ischemia requiring urgent revascularization, or thrombotic bailout was 1.13 (1.04–1.23) and for 30-day death or MI was 1.13 (1.04–1.22). Increasing age was also associated with greater 1-year mortality (adjusted hazard ratio per 10 years: 1.44, 95% CI 1.30–1.60). There was no interaction between age and treatment (p interaction = 0.99, 0.54, and 0.87, respectively). Increasing age was associated with more non‐coronary artery bypass grafting-related TIMI major bleeding (adjusted OR and 95% CI per 10 years: 1.54 [1.24–1.92]), GUSTO moderate/severe bleeding (1.52 [1.33–1.75]), and transfusion (1.25 [1.07–1.45]). The amount by which TIMI major bleeding was increased with early vs. delayed provisional eptifibatide use was significantly greater with increasing age (p interaction = 0.02), but the age × treatment interactions were not significant for GUSTO moderate/severe bleeding or transfusion (p interaction = 0.33 and 0.54, respectively).

Conclusion

Increasing age was associated with greater risk for ischemic events and more bleeding. Despite higher baseline ischemic risk in older patients, there was no preferential benefit of early vs. delayed provisional eptifibatide use for ischemic outcomes as age increased, but the incremental bleeding risk was amplified.     

Impact of distal embolization on myocardial perfusion and survival among patients undergoing primary angioplasty with glycoprotein IIb–IIIa inhibitors: insights from the EGYPT cooperation

Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb–IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ‘‘cutoff’’ in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2–3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 ± 356 U/l vs. 259 ± 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2–3 (adjusted OR [95% CI] = 3.14 [2.06–4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84–1.92], P = 0.26). At 208 ± 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73–6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1–4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb–IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.     

Intracoronary glycoprotein IIb/IIIa inhibitor infusion via a perfusion coronary catheter to decrease thrombus burden: Results from the ClearWay™ Multicenter Registry

ObjectivesThis multicenter registry aimed to assess the ClearWay? (CW) perfusion catheter in reduction of thrombus burden and improvement of the coronary flow during percutaneous coronary intervention (PCI).BackgroundThe presence or development of thrombus during PCI is associated with poor prognosis.MethodsThe utility of the CW perfusion catheter was assessed in patients who presented with intracoronary thrombus and were subjected to PCI. Data were collected by online survey from 15 US sites. Angiographic assessment of the coronary thrombus burden and the coronary flow after intracoronary infusion of glycoprotein (GP) IIb/IIIa inhibitors via the CW catheter was evaluated at baseline, immediately after infusion, and at the end of the procedure. The cohort included 102 patients; 71.6% presented with ST-elevation myocardial infarction (MI), 21.6% with non-ST-elevation MI, 5.9% with stable angina pectoris, and 2.9% with silent ischemia. The mean cohort age was 59.9 ± 14.5 years and comprised mostly of men (72.5%).ResultsGP IIb/IIIa inhibitors were infused via the CW catheter on average 1.1 ± 0.3 times, with a mean pressure of 4.2 ± 2.7 atm and a mean infusion time of 55 ± 55 s. Following the infusion, Thrombolysis In Myocardial Infarction (TIMI) flow improved by 1° in 71 patients (69.6%) and by 2° in 51 patients (50%), while visible thrombus was reduced by 52% (p < 0.001). In the final angiogram, TIMI flow was restored in 90.2% and clearance of a visible thrombus was obtained in 91.8% of the lesions.ConclusionIntracoronary infusion of GP IIb/IIIa inhibitors via the perfusion CW catheter is associated with significant reduction in thrombus burden and with improvement of the coronary flow in patients presenting or developing thrombus burden during PCI.