Cynthia M. Westerhout

Statins Are Associated With a Reduced Incidence of Perioperative Mortality in Patients Undergoing Major Noncardiac Vascular Surgery

Background—Patients undergoing major vascular surgery are at increased risk of perioperative mortality due to underlying coronary artery disease. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (statins) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. Methods and Results—To evaluate the association between statin use and perioperative mortality, we performed a case-controlled study among the 2816 patients who underwent major vascular surgery from 1991 to 2000 at the Erasmus Medical Center. Case subjects were all 160 (5.8%) patients who died during the hospital stay after surgery. From the remaining patients, 2 controls were selected for each case and were stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. A vascular complication during the perioperative phase was the primary cause of death in 104 (65%) case subjects. Statin therapy was significantly less common in cases than in controls (8% versus 25%;P <0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. Conclusion—This case-controlled study provides evidence that statin use reduces perioperative mortality in patients undergoing major vascular surgery.

Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial

AIMS To examine the incidence of and propensity for non-culprit interventions performed at the time of the primary percutaneous coronary intervention (PCI) and its association with 90-day outcomes. METHODS AND RESULTS We examined the incidence, propensity for, and associated 90-day outcomes following non-culprit interventions performed at the time of primary PCI among ST-elevation myocardial infarction patients with multi-vessel coronary artery disease (MVD). Of the 5373 patients who underwent primary PCI in the APEX-AMI trial, 2201 had MVD. Of those, 217 (9.9%) underwent non-infarct-related arteries (IRA) PCI, whereas 1984 (90.1%) underwent PCI of the IRA alone. Ninety-day death and death/CHF/shock were higher in the non-IRA group compared with the IRA-only PCI group (12.5 vs. 5.6%, P (log-rank) < 0.001 and 17.4 vs. 12.0%, P (log-rank) = 0.020, respectively). After adjusting for patient and procedural characteristics as well as propensity for performing non-IRA PCI, this procedure remained independently associated with an increased hazard of 90-day mortality [adjusted hazard ratio 2.44, 95% CI (1.55-3.83), P < 0.001]. CONCLUSION Non-culprit coronary interventions were performed at the time of primary PCI in 10% of MVD patients and were significantly associated with increased mortality. Our data support current guideline recommendations discouraging the performance of such procedures in stable primary PCI patients. Prospective randomized study of this issue may be warranted.

ST-Segment Recovery and Outcome After Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction Insights From the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) Trial

Background— Primary percutaneous coronary angioplasty is an effective and widely adopted treatment for acute myocardial infarction. A simple method of determining prognosis after primary percutaneous coronary intervention (PCI) would facilitate appropriate care and expedite hospital discharge. Thus, we determined the prognostic importance of various measures of ST-segment–elevation recovery after primary PCI in a large, contemporary cohort of patients with ST-elevation myocardial infarction. Methods and Results— We analyzed ECG data describing the magnitude and extent of ST-segment elevation and deviation before and early after (ie, 30 minutes) primary PCI in the study cohort of 4866 subjects with electrocardiographically high-risk ST-elevation myocardial infarction enrolled in the Assessment of PEXelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Associations among 6 methods for calculating ST-segment recovery, biomarker estimates of infarct size (ie, peak creatine kinase, creatine kinase-MB, and troponin I and T), and prespecified clinical outcomes (ie, rates of 90-day death and 90-day death, heart failure, or shock) were examined. All ST-segment–recovery methods provided strong prognostic information regarding clinical outcomes. A simple ST-segment–recovery method of residual ST-segment elevation measurement in the most affected lead on the post-PCI ECG performed as well as complex methods that required comparison of pre- and post-PCI ECGs or calculation of summed ST-segment deviation in multiple leads (ie, worst-lead residual ST elevation: adjusted hazard ratio for 90-day death rate [reference <1 mm]: 1 to <2 mm, 1.23 [95% CI 0.74 to 2.03]; ≥2 mm, 2.22 [95% CI 1.35 to 3.65], corrected c-index=0.832; 90-day death/congestive heart failure/shock [reference <1 mm]: 1 to <2 mm, 1.55 [95% CI 1.06 to 2.26]; ≥2 mm, 2.33 [95% CI 1.59 to 3.41], corrected c-index=0.802). Biomarker estimates of infarct size declined in association with enhanced ST-segment recovery. Conclusions— An ECG performed early after primary PCI is a simple, widely available, inexpensive, and powerful prognostic tool applicable to patients with ST-elevation myocardial infarction.

Acute heart failure in the emergency department: Short and long-term outcomes of elderly patients with heart failure

Previous epidemiologic studies of acute heart failure (AHF) have involved patients admitted to hospital and fail to account for that unknown proportion discharged directly from the emergency department (ED). We examined discharge rates, and whether outcomes, including mortality, differed based on admission status in AHF.

The influence of time from symptom onset and reperfusion strategy on 1-year survival in ST-elevation myocardial infarction: a pooled analysis of an early fibrinolytic strategy versus primary percutaneous coronary intervention from CAPTIM and WEST.

BACKGROUND The CAPTIM trial suggested a survival benefit of prehospital fibrinolysis (FL) compared to primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) with a presentation delay of <2 hours. We examined the relationship between reperfusion strategy and time from symptom onset on 1-year mortality in a combined analysis of 1,168 patients with STEMI. METHODS Individual patient data from CAPTIM (n = 840, 1997-2000) and the more recent WEST trial (n = 328, 2003-2005) were pooled. RESULTS Median age was 58 years, 81% were men, and 41% had anterior myocardial infarction; 640 patients were randomized to FL versus 528 patients to PCI. Both arms received contemporary adjunctive medical therapy. Presentation delay (ie, symptom onset to randomization) was similar in FL and PCI patients (median 105 [72-158] vs 106 [74-162] minutes, P = .712). Rescue PCI after FL occurred in 26% and 27%, and 30-day PCI, in 70% and 71% in CAPTIM and WEST, respectively. Mortality was not different between FL and PCI (4.6% vs 6.5%, P = .263); however, the interaction between presentation delay and treatment was significant (P = .043). Benefit with FL was observed with time <2 hours (2.8% [FL] vs 6.9% [PCI], P = .021, hazard ratio [HR] 0.43, 95% CI 0.20-0.91), whereas beyond 2 hours, no treatment difference was observed (6.9% [FL] vs 6.0% [PCI], P = .529, HR 1.23, 95% CI 0.61-2.46). CONCLUSIONS A strategy of early FL demonstrated a reduction in 1-year mortality compared to primary PCI in early presenters. Time from symptom onset should be a key consideration when selecting reperfusion therapy for STEMI.

Differences in admission rates and outcomes between men and women presenting to emergency departments with coronary syndromes

Background: Previous studies examining sex-related differences in the treatment of coronary artery disease have focused on patients in hospital. We sought to examine sex-related differences at an earlier point in care — presentation to the emergency department. Methods: We collected data on ambulatory care and hospital admissions for 54 134 patients (44% women) who presented to an emergency department in Alberta between July 1998 and March 2001 because of acute myocardial infarction, unstable angina, stable angina or chest pain. We used logistic regression and Cox regression analyses to determine sex-specific associations between the likelihood of discharge from the emergency department or coronary revascularization within 1 year and 1-year mortality after adjusting for age, comorbidities and socioeconomic factors. Results: Following the emergency department visit, 91.3% of patients with acute myocardial infarction, 87.4% of those with unstable angina, 40.7% of those with stable angina and 19.8% of those with chest pain were admitted to hospital. Women were more likely than men to be discharged from the emergency department: adjusted odds ratio (and 95% confidence interval [CI]) 2.25 (1.75–2.90) for acute myocardial infarction, 1.71 (1.45–2.01) for unstable angina, 1.33 (1.15–1.53) for stable angina and 1.46 (1.36–1.57) for chest pain. Women were less likely than men to undergo coronary revascularization within 1 year: adjusted odds ratio (and 95% CI) 0.65 (0.57–0.73) for myocardial infarction, 0.39 (0.35–0.44) for unstable angina, 0.35 (0.29–0.42) for stable angina and 0.32 (0.27–0.37) for chest pain. Female sex had no impact on 1-year mortality among patients with acute myocardial infarction; it was associated with a decreased 1-year mortality among patients with unstable angina, stable angina and chest pain: adjusted hazard ratio (and 95% CI) 0.60 (0.46–0.78), 0.60 (0.46–0.78) and 0.74 (0.63–0.87) respectively. Interpretation: Women presenting to the emergency department with coronary syndromes are less likely than men to be admitted to an acute care hospital and to receive coronary revascularization procedures. These differences do not translate into worse outcomes for women in terms of 1-year mortality.

Use of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention: insights from the APEX-AMI trial

AIMS Controversy exists regarding the early use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial provides a unique opportunity to examine early vs. late or non-use of GPIs in a large STEMI cohort treated with PCI. METHODS AND RESULTS In the APEX-AMI trial, 3969 of 5707 patients received one of three GPIs at the operators discretion (abciximab, eptifibatide, tirofiban). Of GPI-treated patients, the median time from symptom onset to GPI administration was 180 min (25th, 75th percentile: 130, 258); 1125 received the agent prior to arriving in the catheterization laboratory [pre-sheath; GPI to sheath insertion: 37 min (16, 66)], whereas 2844 patients were treated after arrival in the catheterization laboratory [in-lab; sheath insertion to GPI: 16 min (10, 27)]. The pre-sheath use of GPIs was associated with a significantly lower hazard of 90-day mortality [adjusted hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.48-0.95, P = 0.025] and of 90-day composite of death/CHF/shock (adjusted HR 0.81, 95% CI 0.65-1.00, P = 0.054). In-hospital severe and moderate bleeding was not related to the use of GPIs. CONCLUSION This retrospective analysis from a large patient cohort with acute STEMI undergoing PCI suggests that pharmacological pre-treatment of PCI with GPIs, particularly abciximab, was associated with significantly lower occurrence of 90-day clinical outcomes and supports the pre-procedural administration of GPIs in this clinical setting.

Baseline Q-Wave Surpasses Time From Symptom Onset as a Prognostic Marker in ST-Segment Elevation Myocardial Infarction Patients Treated With Primary Percutaneous Coronary Intervention

OBJECTIVES We assessed the incremental value of baseline Q waves over time from symptom onset as a marker of clinical outcome in ST-segment elevation myocardial infarction (STEMI). BACKGROUND Time from symptom onset is a central focus in STEMI patients. The presence of Q waves on the baseline electrocardiogram (ECG) has been suggested to be of incremental value to time from symptom onset in evaluating clinical outcomes. METHODS We evaluated baseline Q waves and ST-segment resolution 30 min after primary percutaneous intervention (PCI) ECGs in 4,530 STEMI patients without prior infarction. Additionally, peak biomarkers; 90-day mortality; and the composite of death, congestive heart failure (CHF), or cardiogenic shock were assessed. RESULTS Fifty-six percent of patients had baseline Q waves: they were older, more frequently male and diabetic, and had a more advanced Killip class. Patients with baseline Q waves had greater mortality and a higher composite rate of death, CHF, and shock versus patients without baseline Q waves at 90 days (5.3% vs. 2.1% and 12.1% vs. 4.8%, respectively, both p < 0.001). Complete ST-segment resolution was highest, whereas 90-day mortality and the composite outcome were lowest among those randomized < or =3 h without baseline Q waves. After multivariable adjustment, baseline Q-wave but not time from symptom onset was significantly associated with a 78% relative increase in the hazard of 90-day mortality and a 90% relative increase in the hazard of death, shock, and CHF. CONCLUSIONS Baseline Q waves in STEMI patients treated with primary PCI provide an independent prognostic marker of clinical outcome. These data might be useful in designing future clinical trials as well as in evaluating patients for triage and potential transfer for planned primary PCI. (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction [APEX-AMI]; NCT00091637).

Reperfusion after primary angioplasty for ST-elevation myocardial infarction: predictors of success and relationship to clinical outcomes in the APEX-AMI angiographic study.

AIMS We studied the clinical, demographic, and angiographic factors associated with successful reperfusion and the relationship between angiographic indices and clinical outcomes in a subset of the APEX-AMI trial, which tested the efficacy of pexelizumab in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS Among 5745 patients enrolled in the trial, 1018 underwent independent quantitative angiographic evaluation by a core laboratory. Successful epicardial reperfusion was defined as TIMI (thrombolysis in myocardial infarction) flow grade 3 or corrected TIMI frame count (cTFC) <28 frames, and successful myocardial reperfusion as TIMI myocardial perfusion grade (TMPG) 2 or 3. TIMI 3 flow after PCI occurred in 85%, cTFC < 28 in 58% (mean cTFC was 27 +/- 20), and TMPG 2 or 3 in 91%. Overall 90 day clinical outcomes were 2.7% for mortality and 8.2% for the composite of death, congestive heart failure (CHF), or shock. After adjustment for baseline characteristics, TMPG 2/3 after PCI was associated with younger age [odds ratio (OR) for 10 year increase 0.75, 95% confidence interval (CI) 0.59-0.96, P = 0.023], pre-PCI TIMI flow 2/3 (OR 3.5, 95% CI 1.7-7.1, P = 0.001), and ischaemic time [for every hour, OR 0.81 (0.69-0.96), P = 0.015]. TMPG 2/3 after PCI was significantly associated with 90 day mortality (adjusted hazard ratio 0.26, 95% CI 0.09-0.78, P = 0.013). Neither post-PCI TMPG nor TIMI flow grade was significantly associated with 90 day death/CHF/shock. CONCLUSION Younger age, patent infarct-related artery at presentation, and ischaemic time predicted higher likelihood of successful myocardial perfusion, which was associated with improved survival.

Mortality and Morbidity Reduction by Primary Percutaneous Coronary Intervention Is Independent of the Patient's Age

OBJECTIVES The aim of this study was to obtain a valid estimate of the clinical effects of primary percutaneous coronary intervention (PPCI) in relation to age. BACKGROUND Treatment with PPCI is most beneficial in high-risk myocardial infarction patients. Paradoxically, elderly patients, who are at increased risk of adverse outcome, are often withheld PPCI. METHODS Individual patient data were obtained from 22 randomized trials (n = 6,763) evaluating the clinical effects of PPCI versus fibrinolysis (FL). Differences in 30-day death, repeat myocardial infarction, and stroke between patients randomized to FL and PPCI were determined in 5 age-strata: < or =50, >50 to 60, >60 to 70, >70 to 80, and >80 years. Treatment effects are reported as odds ratios (ORs) and 95% confidence intervals (CI). Multivariable logistic regression analyses, which included age x treatment interaction, were applied to examine evidence of heterogeneity in age-specific ORs. RESULTS Thirty-day death increased with increasing age and ranged from 1.1% (FL) and 1.8% (PPCI) in patients < or =50 years to 26.4% and 18.3% in patients >80 years of age. The point estimate of treatment effect (overall adjusted OR: 0.65; 95% CI: 0.52 to 0.79) was compatible with a mortality reduction favoring PPCI in all age-strata (except in patients < or =50 years of age), and 95% CIs were largely overlapping. There was no evidence of heterogeneity in ORs between age categories. Similar results were observed for repeat myocardial infarction and stroke. CONCLUSIONS In this analysis of randomized trials, the reduction in clinical end points by PPCI was not influenced by age. Hence, age per se should not be considered an exclusion criterion for the application of PPCI.