Rajendra H. Mehta

Dose comparisons of clopidogrel and aspirin in acute coronary syndromes

BACKGROUNDnClopidogrel and aspirin are widely used for patients with acute coronary syndromes and those undergoing percutaneous coronary intervention (PCI). However, evidence-based guidelines for dosing have not been established for either agent.nnnMETHODSnWe randomly assigned, in a 2-by-2 factorial design, 25,086 patients with an acute coronary syndrome who were referred for an invasive strategy to either double-dose clopidogrel (a 600-mg loading dose on day 1, followed by 150 mg daily for 6 days and 75 mg daily thereafter) or standard-dose clopidogrel (a 300-mg loading dose and 75 mg daily thereafter) and either higher-dose aspirin (300 to 325 mg daily) or lower-dose aspirin (75 to 100 mg daily). The primary outcome was cardiovascular death, myocardial infarction, or stroke at 30 days.nnnRESULTSnThe primary outcome occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; 95% confidence interval [CI], 0.83 to 1.06; P=0.30). Major bleeding occurred in 2.5% of patients in the double-dose group and in 2.0% in the standard-dose group (hazard ratio, 1.24; 95% CI, 1.05 to 1.46; P=0.01). Double-dose clopidogrel was associated with a significant reduction in the secondary outcome of stent thrombosis among the 17,263 patients who underwent PCI (1.6% vs. 2.3%; hazard ratio, 0.68; 95% CI, 0.55 to 0.85; P=0.001). There was no significant difference between higher-dose and lower-dose aspirin with respect to the primary outcome (4.2% vs. 4.4%; hazard ratio, 0.97; 95% CI, 0.86 to 1.09; P=0.61) or major bleeding (2.3% vs. 2.3%; hazard ratio, 0.99; 95% CI, 0.84 to 1.17; P=0.90).nnnCONCLUSIONSnIn patients with an acute coronary syndrome who were referred for an invasive strategy, there was no significant difference between a 7-day, double-dose clopidogrel regimen and the standard-dose regimen, or between higher-dose aspirin and lower-dose aspirin, with respect to the primary outcome of cardiovascular death, myocardial infarction, or stroke. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00335452.)

Improving quality of care for acute myocardial infarction. The Guidelines Applied in Practice (GAP) initiative

CONTEXTnQuality of care of patients with acute myocardial infarction (AMI) has received intense attention. However, it is unknown if a structured initiative for improving care of patients with AMI can be effectively implemented at a wide variety of hospitals.nnnOBJECTIVEnTo measure the effects of a quality improvement project on adherence to evidence-based therapies for patients with AMI.nnnDESIGN AND SETTINGnThe Guidelines Applied in Practice (GAP) quality improvement project, which consisted of baseline measurement, implementation of improvement strategies, and remeasurement, in 10 acute-care hospitals in southeast Michigan.nnnPATIENTSnA random sample of Medicare and non-Medicare patients at baseline (July 1998--June 1999; n = 735) and following intervention (September 1--December 15, 2000; n = 914) admitted at the 10 study centers for treatment of confirmed AMI. A random sample of Medicare patients at baseline (January--December 1998; n = 513) and at remeasurement (March--August 2001; n = 388) admitted to 11 hospitals that volunteered, but were not selected, served as a control group.nnnINTERVENTIONnThe GAP project consisted of a kickoff presentation; creation of customized, guideline-oriented tools designed to facilitate adherence to key quality indicators; identification and assignment of local physician and nurse opinion leaders; grand rounds site visits; and premeasurement and postmeasurement of quality indicators.nnnMAIN OUTCOME MEASURESnDifferences in adherence to quality indicators (use of aspirin, beta-blockers, and angiotensin-converting enzyme [ACE] inhibitors at discharge; time to reperfusion; smoking cessation and diet counseling; and cholesterol assessment and treatment) in ideal patients, compared between baseline and postintervention samples and among Medicare patients in GAP hospitals and the control group.nnnRESULTSnIncreases in adherence to key treatments were seen in the administration of aspirin (81% vs 87%; P =.02) and beta-blockers (65% vs 74%; P =.04) on admission and use of aspirin (84% vs 92%; P =.002) and smoking cessation counseling (53% vs 65%; P =.02) at discharge. For most of the other indicators, nonsignificant but favorable trends toward improvement in adherence to treatment goals were observed. Compared with the control group, Medicare patients in GAP hospitals showed a significant increase in the use of aspirin at discharge (5% vs 10%; P<.001). Use of aspirin on admission, ACE inhibitors at discharge, and documentation of smoking cessation also showed a trend for greater improvement among GAP hospitals compared with control hospitals, although none of these were statistically significant. Evidence of tool use noted during chart review was associated with a very high level of adherence to most quality indicators.nnnCONCLUSIONSnImplementation of guideline-based tools for AMI may facilitate quality improvement among a variety of institutions, patients, and caregivers. This initial project provides a foundation for future initiatives aimed at quality improvement.

Acute type A aortic dissection in the elderly: clinical characteristics, management, and outcomes in the current era

OBJECTIVESnWe sought to evaluate the clinical characteristics, management, and outcomes of elderly patients with acute type A aortic dissection.nnnBACKGROUNDnFew data exist on the clinical manifestations and outcomes of acute type A aortic dissection in an elderly patient cohort.nnnMETHODSnWe categorized 550 patients with type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection into two age strata (<70 and >or=70 years) and compared their clinical features, management, and in-hospital events.nnnRESULTSnThirty-two percent of patients with type A dissection were aged >or=70 years. Marfan syndrome was exclusively associated with dissection in the young, whereas hypertension, atherosclerosis and iatrogenic dissection predominated in older patients. Typical symptoms (abrupt onset of chest or back pain) and signs (aortic regurgitation murmur or pulse deficits) of dissection were less common among the elderly. Fewer elderly patients were managed surgically than younger patients (64% vs. 86%, p < 0.0001). Hypotension occurred more frequently (46% vs. 32%, p = 0.002) and focal neurologic deficits less frequently (18% vs. 26%, p = 0.04) among the elderly. In-hospital mortality was higher among older patients (43% vs. 28%, p = 0.0006). Logistic regression analysis identified age >or=70 years as an independent predictor of hospital death for acute type A aortic dissection (odds ratio 1.7, 95% confidence interval 1.1-2.8; p = 0.03).nnnCONCLUSIONSnOur study shows significant differences between older (age >or=70 years) and younger (age <70 years) patients with acute type A aortic dissection in their clinical characteristics, management, and hospital outcomes. Future research should evaluate strategies to improve outcomes in this high-risk elderly cohort.

Acute Myocardial Infarction in the Elderly: Differences by Age

OBJECTIVESnWe evaluated the clinical characteristics and outcomes of elderly patients hospitalized with acute myocardial infarction (AMI) to describe differences by age.nnnBACKGROUNDnElderly patients with AMI are perceived as a homogeneous population, though the extent by which clinical characteristics vary among elderly patients has not been well described.nnnMETHODSnData from 163,140 hospital admissions of Medicare beneficiaries age > or =65 years between 1994 and 1996 with AMI at U.S. hospitals were evaluated for differences in clinical characteristics and mortality across five age-based strata (in years): 65 to 69, 70 to 74, 75 to 79, 80 to 84 and > or =85.nnnRESULTSnOlder age was associated with a greater proportion of patients with functional limitations, heart failure, prior coronary disease and renal insufficiency and a lower proportion of male and diabetic patients. Of note, the proportion of patients presenting with chest pain within 6 h of symptom onset, and with ST-segment elevation, was lower in each successive age group. Thirty-day mortality rates were higher in older age groups (65 to 69: 10.9%, 70 to 74: 14.1%, 75 to 79: 18.5%, 80 to 84: 23.2%, > or =85: 31.2%, p = 0.001 for trend). The effect of age persisted but was attenuated after adjustment for differences in patient characteristics; similar trends were observed for one-year mortality.nnnCONCLUSIONSnOur data indicate significant age-associated differences in clinical characteristics in elderly patients with AMI, which account for some of the age-associated differences in mortality. The practice of grouping older patients together as a single age group may obscure important age-associated differences.

Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors.

OBJECTIVESnThe purpose of this study was to examine the in-hospital outcome and influence of glycoprotein (GP) IIb/IIIa antagonists on patients with acute coronary syndromes (ACS) across a range of renal function.nnnBACKGROUNDnRecent studies demonstrate increasing cardiovascular risk with progressive renal dysfunction. Previous studies investigating GP IIb/IIIa antagonist use have excluded patients with renal dysfunction.nnnMETHODSnPatients presenting with ACS between January 1999 and May 2000 were identified, and data on demographics, in-hospital management, and clinical events were collected using standardized definitions. Patients were stratified according to renal function assessed by calculated creatinine clearance (CrCl) at presentation. Primary outcome measures included in-hospital mortality and major bleeding events.nnnRESULTSnRenal insufficiency was present in 312 of 889 patients. There were 40 in-hospital deaths. In non-dialysis-dependent patients, as CrCl worsened, there was a decline in utilization of routine diagnostics and therapeutics, an increase in in-hospital mortality (p = 0.002), and an increase in major bleeding (p = 0.03). Although the use of GP IIb/IIIa antagonists was associated with an increase in major bleeding (p < 0.001), there was a protective effect on in-hospital mortality (p = 0.04) after controlling for CrCl.nnnCONCLUSIONSnRenal dysfunction is present in a substantial proportion of patients with ACS and is associated with increased in-hospital death. Although GP IIb/IIIa antagonist use in patients with ACS and renal insufficiency resulted in increased bleeding events, its administration was associated with a decreased risk of in-hospital mortality. These preliminary findings need to be confirmed in future randomized clinical trials.

Iatrogenic aortic dissection

Given the difference in risk factors, clinical presentation, and outcomes, clinicians should be vigilant for the presence of iatrogenic AD, particularly in those patients with unexplained hemodynamic instability or myocardial ischemia following invasive vascular procedures or CABG.

Effects of age on the quality of care provided to older patients with acute myocardial infarction.

PURPOSEnOlder patients are less likely to receive guideline-recommended medical therapies during acute myocardial infarction. However, it is unclear whether the lower rates of treatment reflect elderly patients increased number of comorbid conditions, physician or hospital effects, or true age-associated variation. Furthermore, it is unclear whether age-associated variations in care are similar or vary among treatments.nnnMETHODSnWe evaluated 146,718 Medicare patients from the Cooperative Cardiovascular Project aged > or =65 years who were hospitalized between 1994 and 1996 with a confirmed myocardial infarction, to ascertain whether rates of acute reperfusion therapy and use of aspirin (admission, discharge), beta-blockers (admission, discharge), and angiotensin-converting enzyme (ACE) inhibitors varied among patients aged 65 to 69 years, 70 to 74 years, 75 to 79 years, 80 to 84 years, and > or =85 years. We identified patients who were considered eligible for each therapy and who had no treatment contraindications. Associations between age and use of therapy were assessed, adjusting for patient, physician, hospital, and geographic factors.nnnRESULTSnAdjusted treatment rates were higher for patients aged 65 to 69 years than for patients aged > or =85 years for acute reperfusion therapy (54.4% vs. 31.2%, P <0.0001 for trend), beta-blockers (admission: 52.2% vs. 43.8%, P <0.0001 for trend; discharge: 61.8% vs. 55.3%, P <0.0001 for trend), aspirin at admission (73.8% vs. 71.0%, P <0.0001 for trend), and ACE inhibitors (61.6% vs. 57.1%, P = 0.02 for trend); there were no differences in the prescription of aspirin at discharge (76.0% vs. 73.6%, P = 0.05).nnnCONCLUSIONnElderly patients are less likely to receive guideline-indicated therapies when hospitalized with myocardial infarction. The effects of age were largest for acute reperfusion and smallest for aspirin.

Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation

Objective: To assess variables associated with the occurrence of atrial fibrillation (AF) and the relation of AF with short- and long-term outcomes and with other in-hospital complications in patients with acute coronary syndromes (ACS) with and without ST-segment elevation. Design: Pooled database of 120u2009566 patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation (NSTE) ACS enrolled in 10 clinical trials. Multivariable logistic regression and Cox proportional hazards modelling were used to identify factors associated with AF and its relation with clinical outcomes. Setting: ACS complicated by AF. Patients: 120u2009566 patients with STEMI and NSTE-ACS in 10 clinical trials. Interventions: None evaluated. Main outcome measure: Short- and long-term mortality. Results: Occurrence of AF was 7.5% in the overall population (STEMI 8.0% (nu200a=u200a84u2009161); NSTE-ACSu200a=u200a6.4% (nu200a=u200a36u2009405)). Seven-day mortality was higher for patients with AF (5.1%) than for those without (1.6%). After adjusting for confounders, association of AF with 7-day mortality was present in STEMI (hazards ratio (HR)u200a=u200a1.65; 95% CI 1.44 to 1.90) and NSTE-ACS (HRu200a=u200a2.30; 95% CI 1.83 to 2.90; p interactionu200a=u200a0.015). Risk of long-term mortality (day 8 to 1 year) was also higher in STEMI (HRu200a=u200a2.37; 95% CI 1.79 to 3.15) and NSTE-ACS (HRu200a=u200a1.67; 95% CI 1.41 to 1.99). AF had a larger impact in NSTE-ACS on risk of short-term mortality (p<0.001), stroke (p<0.001), ischaemic stroke (p<0.001) and moderate or severe bleeding (p<0.001). Conclusions: AF is more common in patients with STEMI. An association of AF with short- and long-term mortality among patients with STEMI and NSTE-ACS was found. Understanding these findings may lead to better care of patients with this common arrhythmia.

Association of Painless Acute Aortic Dissection With Increased Mortality

OBJECTIVEnTo evaluate the clinical characteristics and outcomes of patients with painless acute aortic dissection (AAD).nnnPATIENTS AND METHODSnFor this study conducted from 1997 to 2001, we searched the International Registry of Acute Aortic Dissection to identify patients with painless AAD (group 1). Their clinical features and in-hospital events were compared with patients who had painful AAD (group 2).nnnRESULTSnOf the 977 patients in the database, 63 (6.4%) had painless AAD, and 914 (93.6%) had painful AAD. Patients in group 1 were older than those in group 2 (mean +/- SD age, 66.6 +/- 13.3 vs 61.9 +/- 14.1 years; P = .01). Type A dissection (involving the ascendIng aorta or the arch) was more frequent in group 1 (74.6% vs 60.9%; P = .03). Syncope (33.9% vs 11.7%; P < .001), congestive heart failure (19.7% vs 3.9%; P < .001), and stroke (11.3% vs 4.7%; P = .03) were more frequent presenting signs in group 1. Diabetes (10.2% vs 4.0%; P = .04), aortic aneurysm (29.5% vs 13.1%; P < .001), and prior cardiovascular surgery (48.1% vs 19.7%; P < .001) were also more common in group 1. In-hospital mortality was higher in group 1 (33.3% vs 23.2%; P = .05), especially due to type B dissection (limited to the descending aorta) (43.8% vs 10.4%; P < .001), and the prevalence of aortic rupture was higher among patients with type B dissection in group 1 (18.8% vs 5.9%; P = .04).nnnCONCLUSIONnPatients with painless AAD had syncope, congestive heart failure, or stroke. Compared with patients who have painful AAD, patients who have painless AAD have higher mortality, especially when AAD is type B.

Usefulness of pulse deficit to predict in-hospital complications and mortality in patients with acute type A aortic dissection

Vascular compromise seen with pulse deficits is common in patients with type A dissection. However, patient characteristics and in-hospital outcomes associated with pulse deficits have not been evaluated. Accordingly, we studied 513 patients (mean age 62 +/- 14 years, 65% men) with acute type A aortic dissection enrolled in the International Registry of Acute Aortic Dissection. Pulse deficits, defined as decreased or absent carotid or peripheral pulses as noted by clinicians and later confirmed by diagnostic imaging, at surgery or at autopsy were noted in 154 patients (30%). Age <70 years, male gender, neurologic deficit(s), altered mental status, and hypotension, shock, or tamponade on admission were all significantly higher in patients with than without pulse deficits. The etiology of aortic dissection, clinical symptoms, and imaging findings were similar in the 2 groups. In-hospital complications (hypotension, coma, renal failure, and limb ischemia) and mortality (41% vs 25%, p = 0.0002) were significantly higher in patients with pulse deficit. Cox proportional-hazards regression analysis identified pulse deficit as an independent predictor of 5-day in-hospital mortality (risk ratio 2.73, 95% confidence interval 1.7 to 4.4; p <0.0001). Further, overall mortality rates increased with an increasing number of pulse deficits (p for trend <0.0001). Pulse deficits are common findings in patients with type A aortic dissection and identify those at high risk of in-hospital adverse events. This simple clinical sign should direct physicians to consider a diagnosis of aortic dissection in patients with acute chest pain, and should help identify a subgroup of patients who would benefit from more aggressive strategies.