Amparo Casanova

Routine Early Angioplasty after Fibrinolysis for Acute Myocardial Infarction

BACKGROUND Patients with a myocardial infarction with ST-segment elevation who present to hospitals that do not have the capability of performing percutaneous coronary intervention (PCI) often cannot undergo timely primary PCI and therefore receive fibrinolysis. The role and optimal timing of routine PCI after fibrinolysis have not been established. METHODS We randomly assigned 1059 high-risk patients who had a myocardial infarction with ST-segment elevation and who were receiving fibrinolytic therapy at centers that did not have the capability of performing PCI to either standard treatment (including rescue PCI, if required, or delayed angiography) or a strategy of immediate transfer to another hospital and PCI within 6 hours after fibrinolysis. All patients received aspirin, tenecteplase, and heparin or enoxaparin; concomitant clopidogrel was recommended. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening congestive heart failure, or cardiogenic shock within 30 days. RESULTS Cardiac catheterization was performed in 88.7% of the patients assigned to standard treatment a median of 32.5 hours after randomization and in 98.5% of the patients assigned to routine early PCI a median of 2.8 hours after randomization. At 30 days, the primary end point occurred in 11.0% of the patients who were assigned to routine early PCI and in 17.2% of the patients assigned to standard treatment (relative risk with early PCI, 0.64; 95% confidence interval, 0.47 to 0.87; P=0.004). There were no significant differences between the groups in the incidence of major bleeding. CONCLUSIONS Among high-risk patients who had a myocardial infarction with ST-segment elevation and who were treated with fibrinolysis, transfer for PCI within 6 hours after fibrinolysis was associated with significantly fewer ischemic complications than was standard treatment. (ClinicalTrials.gov number, NCT00164190.)

Understanding Physicians' Risk Stratification of Acute Coronary Syndromes: Insights From the Canadian ACS 2 Registry

BACKGROUND An important treatment-risk paradox exists in the management of acute coronary syndromes (ACSs). However, the process of risk stratification by physicians and its relationship to the management of ACS have not been well studied. Our objective was to examine patient risk assessment by physicians in relation to treatment and objective risk score evaluation and the underlying patient characteristics that physicians consider to indicate high risk. METHODS The prospective Canadian ACS 2 Registry recruited 1956 patients admitted for non-ST-segment elevation ACS in 36 hospitals in October 2002 to December 2003. We recorded patient risk assessment by the treating physician and case management on standardized case report forms and calculated the Thrombolysis in Myocardial Infarction (TIMI), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Global Registry of Acute Cardiac Events (GRACE) risk scores. RESULTS Of the 1956 patients with ACS, 347 (17.8%) were classified as low risk, 822 (42.0%) as intermediate risk, and 787 (40.2%) as high risk by their treating physicians. Patients considered as high risk were more likely to receive aggressive medical therapies and to undergo coronary angiography and revascularization. However, there were only weak correlations between risk assessment by physicians and all 3 validated risk scores. In multivariable analysis, history of stroke, worse Killip class, presence of ST-segment deviation, T-wave inversion, and positive cardiac biomarker status were all independently associated with high-risk categorization by the treating physician, while advanced age and previous coronary bypass surgery were independent negative predictors. There was no significant association between the high-risk category and several established prognosticators, such as history of heart failure, hemodynamic variables, and creatinine level. CONCLUSIONS Contemporary risk stratification of ACS appears suboptimal and may perpetuate the treatment-risk paradox. Physicians may not recognize and incorporate the most powerful adverse prognosticators into overall patient risk assessment. Routine use of validated risk score may enhance risk stratification and facilitate more appropriate tailoring of intensive therapies toward high-risk patients.

Validation of the Global Registry of Acute Coronary Event (GRACE) risk score for in-hospital mortality in patients with acute coronary syndrome in Canada

BACKGROUND The Global Registry of Acute Coronary Event (GRACE) risk score was developed in a large multinational registry to predict in-hospital mortality across the broad spectrum of acute coronary syndromes (ACS). Because of the substantial regional variation and temporal changes in patient characteristics and management patterns, we sought to validate this risk score in a contemporary Canadian population with ACS. METHODS The main GRACE and GRACE(2) registries are prospective, multicenter, observational studies of patients with ACS (June 1999 to December 2007). For each patient, we calculated the GRACE risk score and evaluated its discrimination and calibration by the c statistic and the Hosmer-Lemeshow goodness-of-fit test, respectively. To assess the impact of temporal changes in management on the GRACE risk score performance, we evaluated its discrimination and calibration after stratifying the study population into prespecified subgroups according to enrollment period, type of ACS, and whether the patient underwent coronary angiography or revascularization during index hospitalization. RESULTS A total of 12,242 Canadian patients with ACS were included; the median GRACE risk score was 127 (25th and 75th percentiles were 103 and 157, respectively). Overall, the GRACE risk score demonstrated excellent discrimination (c statistic 0.84, 95% CI 0.82-0.86, P < .001) for in-hospital mortality. Similar results were seen in all the subgroups (all c statistics >/=0.8). However, calibration was suboptimal overall (Hosmer-Lemeshow P = .06) and in various subgroups. CONCLUSIONS GRACE risk score is a valid and powerful predictor of adverse outcomes across the wide range of Canadian patients with ACS. Its excellent discrimination is maintained despite advances in management over time and is evident in all patient subgroups. However, the predicted probability of in-hospital mortality may require recalibration in the specific health care setting and with advancements in treatment.

Treatment gaps in the management of cardiovascular risk factors in patients with type 2 diabetes in Canada

OBJECTIVES To evaluate vascular protection treatment patterns and attainment of the 2003 Canadian Diabetes Associations recommended targets in ambulatory patients with type 2 diabetes. METHODS Between 2005 and 2006, 3002 outpatients with type 2 diabetes were enrolled by 229 primary health care settings across Canada. Baseline characteristics, therapeutic regimens and treatment success - defined as the achievement of a blood pressure (BP) of 13080 mmHg or lower, glycosylated hemoglobin (A1C) of 7% or lower, low-density lipoprotein cholesterol (LDL-C) lower than 2.5 mmolL and total cholesterolhigh-density lipoprotein cholesterol ratio lower than 4.0 - are reported. RESULTS Overall, 46% of individuals had a BP that was above the Canadian Diabetes Associations recommended target. Of these, 11% were untreated, 28% were receiving monotherapy, 38% were not receiving an angiotensin-converting enzyme inhibitor and 16% were not receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Optimal A1C levels were achieved in 53% of patients. Of those who did not attain A1C targets, 3% were not on glucose- lowering pharmacotherapy and 27% were receiving monotherapy. A total of 74% of patients were treated with statins. Overall, 64% and 62%, respectively, met the target LDL-C and the target total cholesterolhigh-density lipoprotein cholesterol ratio. Statins were not prescribed to 43% of patients with LDL-C above target. Antiplatelet therapy was implemented in 81% of patients. In total, 21% achieved the combined targets for BP, A1C and LDL-C. INTERPRETATION A substantial proportion of patients did not achieve guideline-recommended targets and were not receiving evidence- based therapy for vascular protection two years after publication of the Canadian guidelines. More research is warranted, and novel and effective strategies must be tested and implemented to correct this ongoing treatment gap.

Applying the Evidence: Do Patients With Stroke, Coronary Artery Disease, or Both Achieve Similar Treatment Goals?

Background and Purpose— The importance of early and aggressive initiation of secondary prevention strategies for patients with both coronary artery disease (CAD) and cerebrovascular disease (CVD) is emphasized by multiple guidelines. However, limited information is available on cardiovascular protection and stroke prevention in an outpatient setting from community-based populations. We sought to evaluate and compare differences in treatment patterns and the attainment of current guideline-recommended targets in unselected high-risk ambulatory patients with CAD, CVD, or both. Methods— This multicenter, prospective, cohort study was conducted from December 2001 to December 2004 among ambulatory patients in a primary care setting. The prospective Vascular Protection and Guidelines-Oriented Approach to Lipid-Lowering Registries recruited 4933 outpatients with established CAD, CVD, or both. All patients had a complete fasting lipid profile measured within 6 months before enrollment. The primary outcome measure was the achievement of blood pressure (BP) <140/90 mm Hg (or <130/80 mm Hg for patients with diabetes) and LDL cholesterol <2.5 mmol/L (<97 mg/dL) according to the Canadian guidelines in place at that time (similar to the National Cholesterol Education Program’s value of 100 mg/dL). Secondary outcomes include use of antithrombotic, antihypertensive, and lipid-modifying therapies. Results— Of the 4933 patients, 3817 (77%) had CAD only; 647 (13%) had CVD only; and 469 (10%) had both CAD and CVD. Mean±SD age was 67±10 years, and 3466 (71%) were male. Mean systolic and diastolic BPs were 130±16 and 75±9 mm Hg, respectively. Minor but significant differences were observed on baseline BP, total cholesterol, and LDL cholesterol measurements among the 3 groups. Overall, 83% of patients were taking a statin and 93% were receiving antithrombotic therapy (antiplatelet and/or anticoagulant agents). Compared with patients with CAD, those with CVD only were less likely to achieve the recommended BP (45.3% vs 57.3%, respectively; P<0.001) and lipid (19.4% vs 30.5%, respectively; P<0.001) targets. Among patients with CVD only, women were less likely to achieve the recommended BP and lipid targets compared with their male counterparts (for LDL cholesterol <2.5 mmol/L, 18.7% vs 23.8%, respectively; P=0.048). In multivariable analysis, patients with CVD alone were less likely to achieve treatment success (BP or lipid targets) after adjusting for age, sex, diabetes, and use of pharmacologic therapy. Conclusions— Despite the proven benefits of available antihypertensive and lipid-lowering therapies, current management of hypertension and dyslipidemia continues to be suboptimal. A considerable proportion of patients failed to achieve guideline-recommended targets, and this apparent treatment gap was more pronounced among patients with CVD and women. Quality improvement strategies should target these patient subgroups.

Relationship between risk stratification at admission and treatment effects of early invasive management following fibrinolysis: insights from the Trial of Routine ANgioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)

AIMS We sought to determine the effectiveness of early routine percutaneous coronary intervention (PCI) post-fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to baseline risk status. METHODS AND RESULTS In this post hoc subgroup analysis of Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), we stratified 1059 STEMI patients receiving tenecteplase into low-intermediate [Global Registry of Acute Coronary Events (GRACE) risk score<155; n=889] vs. high-risk (GRACE risk score ≥155; n=170) groups, based on the GRACE risk score for in-hospital mortality. There was a significant interaction between treatment assignment and risk status for the composite endpoint of death/re-MI at 30 days (P for interaction<0.001). Compared with the standard treatment, pharmacoinvasive therapy (early routine PCI) was associated with a lower rate of death/re-MI at 30 days in the low-intermediate risk stratum (8.1 vs. 2.9%, P<0.001), but a higher rate of death/re-MI in the high-risk group (13.8 vs. 27.8%, P=0.025). We found similar heterogeneity in the treatment effects on 30-day mortality and death/re-MI at 1 year (P for interaction=0.008 and 0.001, respectively), when the GRACE risk score was analysed as a continuous variable (P for interaction<0.001) and when patients were stratified by the Thrombolysis In Myocardial Infarction (TIMI) risk score (P for interaction=0.001). CONCLUSION We observed a strong heterogeneity in the treatment effects of a pharmacoinvasive strategy after fibrinolysis for STEMI, which is associated with improved outcomes only among patients with a low-intermediate GRACE risk score. Conversely, the early invasive strategy is associated with worse outcomes in high-risk patients. These novel findings should be considered exploratory only and require confirmation in other trials and meta-analyses. CLINICAL TRIAL REGISTRATION INFORMATION http://www.clinicaltrials.gov/ct2/show/NCT00164190 ClinicalTrials.gov number, NCT00164190.

Poor achievement of guidelines-recommended targets in type 2 diabetes: findings from a contemporary prospective cohort study.

Aims:  To prospectively evaluate diabetes management in the primary care setting and explore factors related to guideline‐recommended triple target achievement [blood pressure (BP) ≤ 130/80 mmHg, A1C ≤ 7% and low‐density lipoprotein (LDL)‐cholesterol < 2.5 mmol/l].

Relation Between Hemoglobin Level and Recurrent Myocardial Ischemia in Acute Coronary Syndromes Detected by Continuous Electrocardiographic Monitoring

Anemia has been associated with adverse outcomes in patients with acute coronary syndromes (ACS). However, the underlying pathophysiologic mechanisms have not been well elucidated. We sought to determine the independent relation between the hemoglobin level and recurrent ischemia in patients with non-ST-segment elevation ACS using continuous electrocardiographic monitoring. In the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial, 746 patients presenting with non-ST-segment elevation ACS underwent continuous ST-segment monitoring for 48 hours. The data were analyzed independently at a core laboratory. We stratified the study population according to their hemoglobin level on presentation. The primary outcome of the study was recurrent ischemia, defined as ST-segment shifts on continuous electrocardiographic monitoring. Of the 705 patients with analyzable data, 64 had a baseline hemoglobin level <120 g/L, 259 had a level of 120 to 139 g/L, 315 had a level of 140 to 159 g/L, and 67 had a level >160 g/L. The corresponding rates of recurrent ischemia were 39.1%, 22.0%, 15.6%, and 11.9% (p for trend <0.001). A lower hemoglobin level was associated with advanced age, co-morbidities, and a higher GRACE risk score. In multivariable analysis adjusting for these confounders, lower hemoglobin levels retained a significant independent association with recurrent ischemia (p for trend = 0.004). In conclusion, a lower hemoglobin level at presentation was independently associated with recurrent ischemia detected by continuous electrocardiographic monitoring in the setting of non-ST-segment elevation ACS. This suggests that anemia might predispose patients to recurrent ischemia, which could be an important underlying mediator of worse outcomes in patients with lower hemoglobin levels.

QRS prolongation in patients with acute coronary syndromes

BACKGROUND QRS prolongation with or without bundle branch block (BBB) has been associated with adverse outcome in myocardial infarction; we examined the relationship between QRS duration and outcome in a broad spectrum of patients with acute coronary syndrome (ACS). METHOD AND RESULTS Core laboratory evaluation of the presenting electrocardiogram in Canadian ACS Registry patients (n = 5,003) showed 4,289 (85.7%) had QRS <120 milliseconds, 202 (4.0%) patients had QRS > or =120 milliseconds without BBB, 262 (5.2%) had left BBB (LBBB), and 250 (5.0%) had right BBB. Compared to patients with QRS <120 milliseconds, patients with QRS > or =120 milliseconds without BBB had higher in-hospital (3.5% vs 1.9%, odds ratio [OR] 1.87, 95% CI 0.85-4.09, P = .12) and 1-year mortality (14.9% vs 7.7%, OR 2.10, 95% CI 1.38-3.18, P = .001). In-hospital and 1-year mortality was significantly higher in patients with BBB (eg, LBBB compared with QRS <120 milliseconds) (5.0% vs 1.9%, OR 2.71, 95% CI 1.49-4.94, P = .001, and 23.8% vs 7.7%, OR 3.74, 95% CI 2.72-5.13, P < .001). Analyzed as a continuous variable and after adjustment for validated prognosticators, QRS duration was an independent predictor of 1-year death (OR 1.11, 95% CI 1.06-1.16, P < .001) and death/myocardial infarction (OR 1.06, 95% CI 1.02-1.11, P = .003). However, when using clinically applicable QRS duration evaluation, only LBBB was an independent predictor of 1-year mortality (OR 1.93, 95% CI 1.28-2.90, P = .002). CONCLUSIONS In patients presenting with a broad spectrum of suspected ACS, QRS prolongation-particularly in the setting of LBBB-is an independent predictor of in-hospital and 1-year mortality.

Impact of delayed presentation on management and outcome of non-ST-elevation acute coronary syndromes.

BACKGROUND The impact of delayed presentation on the management and outcomes of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) has not been well studied. Furthermore, the prognostic value of initial biomarker level in relation to the time of presentation has not been determined. METHODS The Canadian ACS II registry was a national, multicenter, prospective observational study of 1,956 patients with NSTE-ACS (October 2002-December 2003). We compared the baseline characteristics, treatment, and outcomes in early (within 6 hours of symptom onset) versus late presenters (>6 hours). A logistic regression model was developed to examine the independent association of late presentation with 1-year mortality. We also evaluated the prognostic value of initial biomarker level in relation to early versus late presentation. RESULTS A total of 1,219 (62.3%) patients presented early, whereas 727 (37.7%) presented late; their rates of in-hospital revascularization were similar (40.5% vs 42.5%, respectively, P = .39). There was also no significant difference in hospital mortality (1.6% vs 2.2%, P = .30) or 1-year mortality (7.6% vs 5.7%, P = .13) between early and late presenters. After adjusting for other prognosticators, late presentation was not an independent predictor of 1-year mortality (adjusted odds ratio 0.78, 95% confidence interval 0.48-1.26, P = .3). Elevated initial biomarker was independently associated with higher 1-year mortality (adjusted odds ratio 2.17, 95% CI 1.31-3.58, P = .002) regardless of whether hospital presentation was early or late (P for interaction = .74). CONCLUSIONS There is still considerable delay between symptom onset of NSTE-ACS and hospital presentation in the contemporary era. In contrast to studies of ST-elevation myocardial infarction, we found no significant differences in the management and outcome of early presenters as compared with late presenters with NSTE-ACS. Nevertheless, measures to reduce patient delay time should continue to be implemented. Initial biomarker status is a useful prognosticator irrespective of the delay time.