Percutaneous coronary intervention (PCI) was performed in 8.1% of aspirin-only patients and 78.9% of aspirin-plus-clopidogrel patients.

At the study end point, clinically significant bleeding (TIMI major bleeding, TIMI minor bleeding, or bleeding requiring medical attention) had occurred in 15.3%, 12.7%, 10.9%, 6.1%, and 3.3% of patients who received a total daily rivaroxaban dose of 20 mg, 15 mg, 10 mg, or 5 mg or placebo, respectively. Bleeding was more frequent in patients receiving aspirin and clopidogrel than in patients receiving aspirin alone.

There was no significant difference in the rate of the composite of death, myocardial infarction (MI), stroke, and ischemia requiring revascularization between patients randomized to rivaroxaban and patients randomized to placebo. However, there was a significant 31% reduction in the risk of death, MI, or stroke in rivaroxaban-treated patients.

In both the aspirin-plus-clopidogrel and aspirin-alone groups, patients taking 2.5 mg or 5.0 mg of rivaroxaban twice daily had a bleeding rate of 1.2%. These dosages were both associated with nonsignificantly lower rates of death/MI/stroke than placebo and were therefore selected for use in a future phase III trial.

Place in Therapy: Current guidelines for the treatment of ACS recommend long-term treatment with warfarin under limited circumstances.^1,2 Guidelines for the management of UA/NSTEMI state that moderate-intensity warfarin combined with low-dose aspirin is more effective than aspirin alone for patients not treated with PCI, but with a higher bleeding risk. ¹ These guidelines also contain a class IIb, level of evidence B, recommendation that warfarin may be a reasonable option for patients with a high risk of ischemic events and a low risk for bleeding who do not need, or are intolerant of, clopidogrel. Warfarin should be continued for patients for whom it is indicated, such as those with atrial fibrillation or a mechanical heart valve. Guidelines for the management of STEMI also recommend warfarin when it is indicated, with a warning that its use with aspirin and/or clopidogrel increases bleeding risk and requires close monitoring. ² The low rate of bleeding associated with the use of low doses of rivaroxaban in combination with aspirin and clopidogrel found in ATLAS ACS-TIMI 46 suggests that it may have potential to replace warfarin in ACS patients who require long-term anticoagulation. The results of phase III trials are needed to determine its place in the management of ACS.

Gibson CM, Mega JL, Hammet CJ, et al. Anti-Xa therapy to lower cardiovascular events in addition to aspirin with or without thienopyridine therapy in subjects with acute coronary syndrome ¡V Thrombolysis in Myocardial Infarction 46 Trial. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA.

References

1. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction). J Am Coll Cardiol. 2007;50:e1¡Ve157.

2. King SB 3rd, Smith SC Jr, Hirshfeld JW Jr, et al. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2007;117:261-295.

Patients with NSTEMI were eligible for the trial if they had at least 2 of the following: age >60 years, positive cardiac biomarkers, and ST-segment change. Patients were randomized to an early invasive strategy (coronary angiography as soon as possible after presentation, followed by PCI or coronary artery bypass grafting [CABG], if indicated, within 24 hours) or a delayed invasive strategy (coronary angiography >36 hours after presentation, followed by PCI or CABG if indicated). The primary outcome measure was the 6-month occurrence of death, recurrent MI, or stroke. A secondary outcome measure was the occurrence of death, recurrent MI, or refractory ischemia. The choice of drug therapy was made by the treating physician.

A total of 3031 patients were enrolled. The median times to coronary angiography in the early and delayed invasive strategy groups were 14 and 50 hours, respectively. PCI was performed in 59.6% of the early invasive group and 55% of the delayed invasive group.

The incidence of the primary outcome of death/MI/stroke at 6 months was not significantly different between the early invasive and delayed invasive groups (9.7% vs 11.4%, hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.68ƒ{1.06, P = 0.15). However, the incidence of the secondary outcome of death/MI/refractory ischemia was significantly lower in the early invasive arm, due primarily to a significant reduction in refractory ischemia (1.0% vs 3.3%, P < 0.00001).

Separate analysis of high-risk patients (GRACE [Global Registry of Acute Coronary Events] risk score >140) found a significant reduction in the primary outcome measure in patients treated with the early invasive strategy (14.1% vs 21.6%, HR 0.65, 95% CI 0.48ƒ{0.88, P = 0.005).

There was no significant difference between treatment groups in the occurrence of major bleeding.

Overall, early and delayed intervention strategies are equally safe and effective in patients with NSTEMI. Among high-risk patients, an early invasive strategy is associated with better outcomes.

Place in Therapy: Previous studies have demonstrated the advantage of an early invasive strategy compared with a delayed invasive or conservative strategy for patients with NSTEMI, but the optimal timing of coronary catheterization has been in doubt. ^1-4 An early invasive strategy was defined as performing cardiac catheterization within 10 days in the FRISC II (Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease II) trial, within 4 to 48 hours in TACTICS-TIMI 18 (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategyƒ{TIMI 18), within 72 hours in RITA 3 (Randomized Intervention Trial of Unstable Angina 3), and within 6 hours in ISAR-COOL (Intracoronary Stenting with Antithrombotic Regimen Cooling-Off Trial). ^1-4 This trial helps clarify the issue and has several real-world applications. Most significantly, it demonstrates the importance of risk stratification for patients with NSTEMI, so that high-risk patients can receive the benefit of early (within 24 hours) intervention. It also demonstrates that early intervention reduces the rate of refractory ischemia. Finally, it shows that, for low-risk patients, delaying catheterization for approximately 48 hours does no harm. Thus a low-risk patient who presents on a weekend does not necessarily require immediate intervention, although it is an acceptable option if it is available.

Mehta S. Randomized comparison of early versus delayed invasive strategies in high risk patients with non-ST segment elevation acute coronary syndromes: main results of the TIMing of intervention in Acute Coronary Syndrome (TIMACS) Trial. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA.

References

1. Wallentin L, Lagerqvist B, Husted S, Kontny F, Stahle E, Swahn E; for the FRISC II Investigators. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. Lancet. 2000;356:9-16.

2. Cannon CP, Weintraub WS, Demopoulos LA, et al; for the TACTICS-Thrombolysis in Myocardial Infarction 18 Investigators. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344:1879-1887.

3. Fox KAA, Poole-Wilson PA, Henderson RA, et al; for the Randomized Intervention Trial of Unstable Angina (RITA) Investigators. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Lancet. 2002;360:743-751.

4. Neumann F-J, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment (¡§cooling-off¡¨ strategy) before intervention in patients with unstable coronary syndromes. A randomized controlled trial. JAMA. 2003;290:1593-1599.

From 2004 to 2006, NRMI enrolled 100,071 NSTEMI patients at 214 OHS and 52 No-OHS hospitals with capability of performing PCI. Use of PCI, administration of guideline-recommended medications, and in-hospital mortality were evaluated in the overall cohort and in a case-control analysis that matched for baseline patient characteristics.

In the overall analysis, patients presenting to OHS hospitals were significantly more likely to receive antiplatelet agents, beta-blockers, and statins within 24 hours of admission and at discharge (P < 0.001 for all). They were also more likely to undergo elective PCI (38.4% vs 14.1%, P < 0.001) and had a lower in-hospital mortality rate (5.0% vs 8.8%, P < 0.001).

In the case-control analysis, patients presenting to OHS hospitals were more likely to receive antiplatelet agents, beta-blockers, and statins (P < 0.001) and had lower mortality (5.9% vs 8.5%, P < 0.001). However, the difference in mortality was attenuated after adjustment for differences in medications and hospital characteristics (HR 1.08, 95% CI 0.90ƒ{1.29, P = 0.41). When only patients undergoing elective PCI were compared, there was no difference in in-hospital mortality at OHS and No-OHS hospitals (1.3% vs 1.0%, P = 0.49).

NSTEMI patients presenting to No-OHS hospitals had significantly higher in-hospital mortality than patients presenting to OHS hospitals, apparently because of hospital characteristics and compliance with guideline-recommended medications within the first 24 hours. Among patients who underwent PCI, there was no difference in in-hospital mortality between patients presenting to OHS and No-OHS hospitals.

Place in Therapy: Previous studies have demonstrated that use of recommended therapies for patients with ACS reduces mortality. An early study established that admission to a top-ranked hospital for treatment of acute MI was associated with lower risk of 30-day mortality, which was attributable to greater use of aspirin and beta-blockers. ¹ Analysis of data from GRACE found a 27% reduction in mortality among ACS patients admitted to hospitals in the top quartile of adherence to guideline-recommended drug therapy compared with patients admitted to hospitals in the bottom quartile. ² In the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of ACC/AHA Guidelines?) registry of UA/NSTEMI patients, it was shown that each 10% improvement in adherence to American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations for use of recommended drugs is associated with a corresponding 10% decrease in mortality. ³ The present study adds to this body of evidence by demonstrating that differences in mortality in NSTEMI patients admitted to hospitals that are or are not equipped to perform open-heart surgery result from the rates of use of recommended medications in the first 24 hours after admission.

Pride YP, Canto JG, Frederick PD, Gibson CM. Outcomes among patients with non-ST-segment elevation myocardial infarction presenting to interventional hospitals with and without on-site cardiac surgery: a NRMI 5 analysis. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 6235.

References

1. Chen J, Radford MJ, Wang Y, Marciniak TA, Krumholz HM. Do ¡§America¡¦s Best Hospitals¡¨ perform better for acute myocardial infarction? N Engl J Med. 1999;340:286-292.

2. Granger CB, Steg PG, Peterson E, et al; for the GRACE Investigators. Medication performance measures and mortality following acute coronary syndromes. Am J Med. 2005;118:858-865.

3. Peterson ED, Roe MT, Mulgund J, et al. Association between hospital process performance and outcomes among patients with acute coronary syndromes. JAMA. 2006;295:1912-1920.

In the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapyƒ{TIMI 28) trial, patients with STEMI who were undergoing fibrinolysis were randomized to receive clopidogrel or placebo to determine the effect on reperfusion of the infarct-related artery. ¹ In 1250 of the CLARITY-TIMI 28 subjects, troponin T (TnT) was measured at baseline and STRes was measured at 90 minutes. The independent association between TnT levels, STRes, and 30-day mortality was determined using multivariable logistic regression.

Among these patients, 594 had undetectable TnT at baseline, 330 had detectable TnT below the median of 0.12 ng/mL, and 326 had TnT above the median. Patients with higher baseline TnT were older, more likely to have a history of hypertension or diabetes, presented later after symptom onset, and were more likely to have anterior MI or Killip class II to IV. Thirty-day rates of cardiovascular death were 1.5%, 4.5%, and 9.5% in the 3 groups, respectively. After adjustment for baseline factors including time to presentation, the odds ratio of 30-day cardiovascular death was 2.79 (95% CI 1.13ƒ{6.88, P = 0.026) for patients with TnT below the median and 6.21 (95% CI 2.64ƒ{14.58, P < 0.0001) for patients with TnT above the median compared with patients with undetectable TnT.

In a multivariable model, both baseline TnT and STRes at 90 minutes were found to be significant predictors of 30-day cardiovascular death.

Place in Therapy: ACC/AHA guidelines for the management of patients with STEMI state that cardiac biomarker measurements provide useful prognostic information and a noninvasive estimate of whether fibrinolysis was successful and can be used to estimate infarct size. ² This study lends support to that view by demonstrating that TnT levels at admission and STRes 90 minutes after reperfusion are predictive of 30-day cardiovascular mortality. Similarly, an analysis of data from the ASSENT-2 (Assessment of Safety and Efficacy of a New Thrombolytic) and ASSENT-PLUS studies found that STEMI patients with elevated admission TnT or STRes <50% after 1 hour had a 1-year mortality rate 3 times higher than patients without those findings. ³ Thus, TnT and STRes can be used to identify patients with elevated short- and long-term risk of cardiovascular death who should be followed closely.

Sherwood MW, Morrow DA, Scirica BM, et al. Baseline troponin levels predict 30 day CV mortality in STEMI independent of clinical and electrocardiographic factors: analysis from CLARITY-TIMI 28. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 977.

References

1. Sabatine MS, Cannon CP, Gibson CM, et al; for the CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352:1179-1189.

2. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation. 2004;110:e82-e292.

3. Bjorklund E, Lindahl B, Johanson P, et al; ASSENT-2 and ASSENT-PLUS Study Groups. Admission troponin T and measurement of ST-segment resolution at 60 min improve early risk stratification in ST-elevation myocardial infarction. Eur Heart J. 2004;25:113-120.

Estimated glomerular filtration rate was <60 mL/min/1.73 m² in 30.5% of patients with STEMI and 42.9% of patients with NSTEMI. Patients with CKD and either STEMI or NSTEMI were less likely than patients without CKD to receive aspirin, beta-blockers, or clopidogrel or to undergo early catheterization, and were more likely to experience major bleeding or death. The relative increase in death with advancing CKD stage was greater in STEMI patients than in NSTEMI patients.

A large proportion of patients with ACS have CKD. They are less likely than patients without CKD to receive evidence-based therapies and are more likely to develop complications or die.

Place in Therapy: Renal impairment is a well-established risk factor for adverse cardiovascular events. In the Framingham study, stage 3 CKD was associated with a 20% increased risk of cardiovascular disease and stage 3b CKD with a 50% increased risk. ¹ This association was modified by the presence or absence of other cardiovascular risk factors. A study of Medicare patients who presented with ACS found that aspirin, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors were less likely to be administered to patients with end-stage renal disease than to other patients. ² Patients on dialysis had a 50% higher rate of 30-day mortality than patients not on dialysis. In patients on dialysis, use of aspirin, beta-blockers, and ACE inhibitors was associated with 50%, 40%, and 48% relative reductions in 30-day mortality, respectively. The present study serves as a reminder that patients with CKD and ACS are at high risk for adverse outcomes and that the treatment of such patients should be more, not less, aggressive.

Fox CS, Muntner P, Chen AY, et al. Short-term outcomes of STEMI and NSTEMI in patients with chronic kidney disease: a report from the National Cardiovascular Data ACTION Registry. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 5577.

References

1. Parikh NI, Hwang S-J, Larson MG, Levy D, Fox CS. Chronic kidney disease as a predictor of cardiovascular disease (from the Framingham Heart Study). Am J Cardiol. 2008;102:47-53.

2. Berger AK, Duval S, Krumholz HM. Aspirin, beta-blocker, and angiotensin-converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction. J Am Coll Cardiol. 2003;42:201-208.

The Canadian ACS II Registry recruited 1956 patients with NSTEMI over a 15-month period. Assessment of patient risk and treatments provided were recorded, and TIMI, PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin [eptifibatide] Therapy), and GRACE risk scores were calculated for each patient. Treating physicians classified 17.8% of patients as low risk, 42% as intermediate risk, and 40.2% as high risk. Although patients considered to be high risk were more likely to receive aggressive medical therapy and to undergo revascularization, there were only weak correlations between risk assessment by physicians and the 3 validated risk scores. Treating physicians incorrectly regarded advanced age as a negative predictor of risk, and history of heart failure, hemodynamic variables, and serum creatinine levels did not affect their risk assessments.

Many physicians do not recognize the most powerful adverse predictors in patients with ACS. Use of validated risk assessment tools may improve risk stratification and target more aggressive treatment strategies to higher-risk patients.

Place in Therapy: The CRUSADE Quality Improvement Initiative has revealed that NSTEMI patients, who by objective measures are considered high risk for adverse outcomes, are less likely than low-risk patients to receive early invasive management strategies. ¹ In a group of 17,926 patients enrolled in CRUSADE, early invasive management was used preferentially in younger patients and those without congestive heart failure or renal insufficiency. ¹ This was consistent with their overall care-patients who were treated with early invasive management were also more likely to receive ACC/AHA guideline-recommended medical therapy and had a lower rate of in-hospital mortality. In another CRUSADE analysis, 28% of high-risk and 51% of low-risk patients underwent PCI, and high-risk patients waited longer for the procedure. ² The current study suggests that this paradoxical use of aggressive management may result from physicians¡¦ inability to accurately assess patients¡¦ risk, as shown by their tendency to put older patients in lower-risk categories and to ignore the influence of heart failure, hemodynamic variables, and serum creatinine. More effective educational efforts are needed that will teach physicians how to risk-stratify NSTEMI patients so that aggressive treatments are provided to the patients who may benefit from them most.

Yan AT, Yan RT, Huynh T, et al. Understanding physicians¡¦ risk stratification of acute coronary syndromes: insights from the Canadian ACS II Registry. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 5585.

References

1. Bhatt DL, Roe MT, Peterson ED, et al; for the CRUSADE Investigators. Utilization of early invasive management strategies for high-risk patients with nonƒ{ST-segment elevation acute coronary syndromes. Results from the CRUSADE Quality Improvement Initiative. JAMA. 2004;292:2096-2104.

2. Zia MI, Goodman SG, Peterson ED, et al. Paradoxical use of invasive cardiac procedures for patients with non-ST segment elevation myocardial infarction: an international perspective from the CRUSADE Initiative and the Canadian ACS Registries I and II. Can J Cardiol. 2007;23:1073-1079.

Aspirin, unfractionated heparin, and eptifibatide were administered to all patients. Median D2R was 59 minutes (interquartile range 49ƒ{70.5 minutes) and median D2B was 65 minutes (interquartile range 53ƒ{75.5 minutes), a statistically significant difference. D2R was shorter than or equal to D2B in 55 patients (81%). In 6 (9%) cases, initial balloon inflation did not establish TIMI 2 to 3 flow and additional device and/or drug therapy was required. In 3 cases, D2B was longer than 90 minutes and D2R was less than 90 minutes. Cases in which D2R was less than D2B were attributable to the effects of drug therapy or guide-wire crossing of the occlusion.

D2B usually overestimates, but occasionally underestimates, D2R, which is a better measure of the success of treatment. Use of D2R to evaluate care of ACS patients may mitigate pressure to perform what may be unnecessary use of device therapy.

Place in Therapy: ACC/AHA guidelines for management of patients with STEMI state that the goal of reperfusion therapy is to minimize total ischemic time, defined as the period from onset of symptoms until initiation of reperfusion therapy. ¹ The guidelines recommend that the time from first medical contact to balloon inflation not exceed 90 minutes. As this study demonstrates, the time to initiation of reperfusion therapy and the time to reperfusion are 2 different things. Reperfusion may occur spontaneously, as a result of drug therapy, or as a result of the guide-wire passage through the occlusion. Thus D2R is a better measure of the success of treatment of STEMI than D2B. However, these other means by which reperfusion may be achieved are unpredictable. D2B was conceived of as a measure of the efficiency of a hospital¡¦s systems and plays an essential role in that process. It is less reliable as a measure of the success of therapy, for which D2R may be useful.

Peterman JM, George A, Giugliano GR, Schweiger MJ. Door-to-balloon time-Are we evaluating the wrong metric? Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 5604.

Reference

1. Antman EM, Hand M, Armstrong PW, et al. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008;51:296-329.

Of the 1409 NSTEMI patients enrolled in PREMIER, 686 would have been excluded from TACTICS-TIMI 18. An early invasive strategy was used for 227 (33%) and a conservative strategy was used for 459 (67%). Propensity score matching identified 174 pairs for comparison. There were no significant differences in baseline characteristics between the early intervention and conservative groups. There was no difference in the rate of 1-year rehospitalization between the 2 groups (HR 1.18, 95% CI 0.79ƒ{1.77). Patients managed with a conservative strategy had a significantly higher rate of 1-year mortality (HR 2.27, 95% CI 1.24ƒ{4.16) and 3-year mortality (HR 1.67, 95% CI 1.06ƒ{2.62).

NSTEMI patients ineligible for inclusion in TACTICS-TIMI 18 would benefit from an early invasive approach.

Place in Therapy: The TACTICS-TIMI 18 trial enrolled 2220 patients with UA/NSTEMI. ¹ All were treated with aspirin, heparin, and a glycoprotein IIb/IIIa inhibitor and were randomized either to undergo cardiac catheterization within 4 to 48 hours with revascularization as appropriate or to a conservative strategy, in which they underwent catheterization only if they had evidence of recurrent ischemia or an abnormal stress test. At 6 months, there was a 22% reduction in the composite rate of death, nonfatal MI, and rehospitalization for ACS in the early intervention group (15.9% vs 19.4%, odds ratio [OR] 0.78, 95% CI 0.62ƒ{0.97, P = 0.025). Exclusion criteria for the trial were persistent ST-segment elevation, secondary angina, history of PCI or CABG within the preceding 6 months, increased bleeding risk, left bundle-branch block or paced rhythm, severe congestive heart failure or cardiogenic shock, serious systemic disease, serum creatinine >2.5 mg/dL, and concurrent participation in another study of an investigational drug or device. Patients taking warfarin or who had received ticlopidine or clopidogrel for >3 days before enrollment were also excluded. Thus, a substantial proportion of patients who present to an emergency department with NSTEMI would not be eligible for this trial. The present analysis establishes that the findings of TACTICS-TIMI 18 extend beyond the trial population and can be applied to patients who would have been excluded.

Sajnani NV, Amin AA, Bach RG, et al. A comparison of early invasive versus conservative therapy for non-ST elevation myocardial infarction patients excluded from clinical trials. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 5615.

Reference

1. Cannon CP, Weintraub WS, Demopoulos LA, et al; for the TACTICS-Thrombolysis in Myocardial Infarction 18 Investigators. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344:1879-1887.

Over a 23-month period, 242 ECGs of patients with suspected STEMI were transmitted via the STAT-MI network. Compared with the period before STAT-MI was in use, door-to-cardiology notification time was reduced from 61.4 to -15.8 min (P < 0.001); door-to-arterial access time was reduced from 108.1 to 42.1 min (P < 0.0001); door-to-intervention (D2I) time was reduced from 145.7 to 68.8 min (P = 0.00001); hospital length of stay was reduced from 5.4 ¡Ó 4.5 days to 4.1 ¡Ó 5.0 days (not significant [NS]); and troponin elevation was reduced from 106.4 ng/mL to 73.9 ng/mL (NS). The time of presentation did not affect the improvement in treatment times, although D2I time was significantly longer if the patient presented after 5:00 PM or on a weekend than if he or she presented during a weekday (85.7 min vs 51.8 min, P = 0.001). During the first 6 months of use of the STAT-MI network, protocol refinements were introduced that further improved D2I time, which was 87 min during the first 6 months and 65 min during the subsequent 17 months (NS).

Transmission of ECGs of patients with suspected STEMI from EMS personnel simultaneously to the ED and an offsite cardiologist reduces D2I times. There were trends toward reduced length of stay and smaller infarct size. Experience gained over the first 6 months of use of the system was useful in refining its use.

Place in Therapy: The time from a STEMI patient¡¦s arrival in the ED until the use of interventional procedures influences the risk of short- and long-term mortality. Analysis of data on more than 29,000 patients enrolled in NRMI showed that in-hospital mortality increased from 3.0% in patients whose D2B time was <90 minutes to 7.4% in patients whose D2B time was >150 minutes. ¹ This finding was independent of time from symptom onset to door and the patient¡¦s risk factor status. In a series of 2322 patients, increasing D2B time was found to be associated with increasing 7-year mortality in high-risk patients. ² Use of the prehospital 12-lead ECG has previously been shown to decrease treatment time. Use of a hand-held device to transmit prehospital ECG data resulted in a reduction in door-to-reperfusion time from 101 minutes to 50 minutes. ³ Transmission of prehospital ECGs is particularly effective if evidence of STEMI triggers activation of the catheterization laboratory before the patient¡¦s arrival. ⁴ The present study adds to the evidence that making ECG data available to treating physicians before the patient¡¦s arrival at the ED improves treatment time.

Maher JM, Dhruva VN, Solanki P, Zakir R, Kaluski E, Klapholz M. ST-Segment Analysis Using Wireless Technology in Acute Myocardial Infarction (STAT-MI) trial: early vs late experience. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 549.

References

1. McNamara RL, Wang Y, Herrin J, et al; for the NRMI Investigators. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2006;47:2180-2186.

2. Brodie BR, Hansen C, Stuckey TD, et al. Door-to-balloon time with primary percutaneous coronary intervention for acute myocardial infarction impacts late cardiac mortality in high-risk patients and patients presenting early after the onset of symptoms. J Am Coll Cardiol. 2006;47:289-295.

3. Adams GL, Campbell PT, Adams JM, et al. Effectiveness of prehospital wireless transmission of electrocardiograms to a cardiologist via hand-held device for patients with acute myocardial infarction (from the Timely Intervention in Myocardial Emergency, NorthEast Experience [TIME-NE]). Am J Cardiol. 2006;98:1160-1164.

4. Brown JP, Mahmud E, Dunford JV, Ben-Yehuda O. Effect of prehospital 12-lead electrocardiogram on activation of the cardiac catheterization laboratory and door-to-balloon time in ST-segment elevation acute myocardial infarction. Am J Cardiol. 2008;101:158-161.

STD was found neither on admission nor at 12 hours in 2617 patients, only at admission in 580 patients, only at 12 hours in 181 patients, and at admission and at 12 hours in 540 patients. At 6 months, the rate of the composite of death or recurrent MI was 15.6%, 17.1%, 21.5%, and 25.7% in the 4 groups, respectively (P < 0.001). After adjustment for treatment assignment, age, gender, ethnicity, presence of diabetes, prior MI, smoking, heart rate, serum creatinine, and cardiac enzymes, STD on admission (HR per 1-mm STD 1.14, 95% CI 1.04ƒ{1.26, P = 0.003) and STD at 12 hours (HR per 1-mm STD 1.17, 95% CI 1.01ƒ{1.35, P = 0.03) each independently predicted death or reinfarction at 6 months.

In patients with NSTEMI, obtaining a routine ECG at 12 hours and quantifying the extent of STD, if present, provides prognostic information potentially helpful in risk stratification beyond that obtained from the admission ECG.

Place in Therapy: The SYNERGY trial randomized 9978 patients with NSTEMI being managed with an early interventional strategy to treatment with enoxaparin or unfractionated heparin. ¹ The 30-day rate of death or nonfatal MI was similar in the 2 treatment groups. However, 75% of patients received some form of anticoagulation before randomization and 8% assigned to one drug received the other drug after randomization. When the subgroup of patients who received the same drug throughout was analyzed, patients who received only enoxaparin had a lower rate of death or nonfatal MI at 30 days than patients who received only heparin (13.3% vs 15.9%; HR 0.82; 95% CI 0.72¡V0.94; adjusted P = 0.041). There was a nonsignificant trend toward an increased risk of bleeding in the enoxaparin group.

STD is an important element in the risk stratification of patients with NSTEMI. It has previously been shown that STD in 3 or more leads or maximal STD >=2 mV identifies patients with chest pain who are at high risk of MI. ² The cumulative sum of STD in all leads predicts 30-day mortality in NSTEMI patients; mortality increases continuously with increasing extent of STD. ³ This analysis of SYNERGY data demonstrates that STD appearing either on the admission ECG or on an ECG obtained 12 hours later is an important prognostic sign.

Yan RT, Yan AT, Mahaffey KW, et al. Prognostic significance of evolving ST-segment depression on admission and early repeat electrocardiograms in non-ST elevation acute coronary syndromes - insights from the superior yield of the new Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitor (SYNERGY) trial. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 550.

References

1. SYNERGY Executive Committee. The SYNERGY trial: study design and rationale. Am Heart J. 2002;143:952-960.

2. Lloyd-Jones DM, Camargo CA, Lapuerta P, Giugliano RP, O¡¦Donnell CJ. Electrocardiographic and clinical predictors of acute myocardial infarction in patients with unstable angina pectoris. Am J Cardiol. 1998;81:1182-1186.

3. Savonitto S, Cohen MG, Politi A, et al. Extent of ST-segment depression and cardiac events in non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2005;26:2106-2113.

Patients who had events had significantly higher levels of NT-proBNP at baseline and 24 hours than patients who did not have events. With the use of the CART model, adjusted for age, gender, and infarct location, Killip class and NT-proBNP could categorize patients into 4 strata with 90-day mortality rates of 4%, 10%, 30%, and 53%. Only 4 patients with a 24-hour NT-proBNP <999 pg/mL had an event within 90 days.

NT-proBNP performed at admission and at 24 hours provides important prognostic information for STEMI patients undergoing PCI.

Place in Therapy: NT-proBNP has been found to have multiple prognostic uses in patients with cardiovascular disease. It is a highly sensitive and specific marker for the diagnosis of congestive heart failure, with utility in the emergency department. ¹ It is an independent predictor of cardiovascular events in heart failure patients with preserved left ventricular ejection fraction. ² In patients with dyspnea, it adds to the information that can be obtained from echocardiography. ³ In patients with stable coronary heart disease, NT-proBNP can be used to identify those who do not have ventricular dysfunction and those who are at high risk for cardiovascular events. ^4,5 The present study demonstrates the usefulness of NT-proBNP in risk-stratifying STEMI patients when it is tested at admission and after 24 hours. Future studies should focus on whether NT-proBNP provides prognostic information beyond that which can be obtained from measuring other cardiac biomarkers.

Ezekowitz JA, Bakal JA, Huber K, et al. NT-proBNP is an important independent predictor of clinical events after primary PCI for STEMI. Presented at: American Heart Association Scientific Sessions; November 8ƒ{12, 2008; New Orleans, LA. Abstract 569.

References

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