Guidelines SCA - Table 7 Flashcards
ASSENT-2
Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction
Background Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase.
Methods In 1021 hospitals, we randomly assigned 16 949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (100 mg) or single- bolus injection of tenecteplase (30–50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50–75 s). The primary outcome was equivalence in all-cause mortality at 30 days.
Findings Covariate-adjusted 30-day mortality rates were almost identical for the two groups—6·18% for tenecteplase and 6·15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0·61% and 10·00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0·93% for tenecteplase and 0·94% for alteplase), but fewer non-cerebral bleeding complications (26·43 vs 28·95%, p=0·0003) and less need for blood transfusion (4·25 vs 5·49%, p=0·0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7·11% with tenecteplase and 7·04% with alteplase (relative risk 1·01 [95% CI 0·91–1·13]).
Interpretation Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.
CAPTIM
Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction
Aims
The CAPTIM (Comparison of primary Angioplasty and Pre-hospital fibrinolysis In acute Myocardial infarction) study found no evidence that a strategy of primary angioplasty was superior in terms of 30-day outcomes to a strategy of pre-hospital fibrinolysis with transfer to an interventional facility in patients managed early at the acute phase of an
acute myocardial infarction. The present analysis was designed to compare both strategies at 5 years.
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Methods and results
The CAPTIM study included 840 patients managed in a pre-hospital setting within 6 h of an acute ST-segment
elevation myocardial infarction. Patients were randomized to either a primary angioplasty (n 1⁄4 421) or a pre-hospital
fibrinolysis (rt-PA) with immediate transfer to a centre with interventional facilities (n 1⁄4 419). Long-term follow-up
was obtained in blinded fashion from 795 patients (94.6%). Using an intent-to-treat analysis, all-cause mortality at
5 years was 9.7% in the pre-hospital fibrinolysis group when compared with 12.6% in the primary angioplasty
group [HR 0.75 (95% CI, 0.50–1.14); P 1⁄4 0.18]. For patients included within 2 h, 5 year mortality was 5.8% in the
pre-hospital fibrinolysis group when compared with 11.1% in the primary angioplasty group [HR 0.50 (95% CI,
0.25–0.97); P 1⁄4 0.04], whereas it was, respectively, 14.5 and 14.4% in patients included after 2 h [HR 1.02, (95%
CI 0.59–1.75), P 1⁄4 0.92]. ……………………………………………………………………………………………………………………………………………………………….
Conclusion The 5-year follow-up is consistent with the 30-day outcomes of the trial, showing similar mortality for primary per- cutaneous coronary intervention and a policy of pre-hospital lysis followed by transfer to an interventional center. In addition, for patients treated within 2 h of symptom onset, 5-year mortality was lower with pre-hospital lysis.
ASSENT-3
Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin
Background Current fibrinolytic therapies fail to achieve optimum reperfusion in many patients. Low-molecular-weight heparins and platelet glycoprotein IIb/IIIa inhibitors have shown the potential to improve pharmacological reperfusion therapy. We did a randomised, open-label trial to compare the efficacy and safety of tenecteplase plus enoxaparin or abciximab, with that of tenecteplase plus weight-adjusted unfractionated heparin in patients with acute myocardial infarction.
Methods 6095 patients with acute myocardial infarction of less than 6 h were randomly assigned one of three regimens: full-dose tenecteplase and enoxaparin for a maximum of 7 days (enoxaparin group; n=2040), half-dose tenecteplase with weight-adjusted low-dose unfractionated heparin and a 12-h infusion of abciximab (abciximab group; n=2017), or full-dose tenecteplase with weight-adjusted unfractionated heparin for 48 h (unfractionated heparin group; n=2038). The primary endpoints were the composites of 30-day mortality, in-hospital reinfarction, or in-hospital refractory ischaemia (efficacy endpoint), and the above endpoint plus in-hospital intracranial haemorrhage or in-hospital major bleeding complications (efficacy plus safety endpoint). Analysis was by intention to treat.
Findings There were significantly fewer efficacy endpoints in the enoxaparin and abciximab groups than in the unfractionated heparin group: 233/2037 (11·4%) versus 315/2038 (15·4%; relative risk 0·74 [95% CI 0·63–0·87], p=0·0002) for enoxaparin, and 223/2017 (11·1%) versus 315/2038 (15·4%; 0·72 [0·61–0·84], p<0·0001) for abciximab. The same was true for the efficacy plus safety endpoint: 280/2037 (13·7%) versus 347/2036 (17·0%; 0·81 [0·70–0·93], p=0·0037) for enoxaparin, and 287/2016 (14·2%) versus 347/2036 (17·0%; 0·84 [0·72–0·96], p=0·01416) for abciximab.
Interpretation The tenecteplase plus enoxaparin or abciximab regimens studied here reduce the frequency of ischaemic complications of an acute myocardial infarction. In light of its ease of administration, tenecteplase plus enoxaparin seems to be an attractive alternative reperfusion regimen that warrants further study.
ASSENT-3 PLUS
Efficacy and Safety of Tenecteplase in Combination With
the Low-Molecular-Weight Heparin Enoxaparin or
Unfractionated Heparin in the Prehospital Setting
Background—The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial infarction.
Methods and Results—In the prehospital setting, 1639 patients with ST-elevation myocardial infarction were randomly assigned to treatment with tenecteplase and either (1) intravenous bolus of 30 mg enoxaparin (ENOX) followed by 1 mg/kg subcutaneously BID for a maximum of 7 days or (2) weight-adjusted unfractionated heparin (UFH) for 48 hours. The median treatment delay was 115 minutes after symptom onset (53% within 2 hours). ENOX tended to reduce the composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia to 14.2% versus 17.4% for UFH (P0.080), although there was no difference for this composite end point plus in-hospital intracranial hemorrhage or major bleeding (18.3% versus 20.3%, P0.30). Correspondingly, there were reductions in in-hospital reinfarction (3.5% versus 5.8%, P0.028) and refractory ischemia (4.4% versus 6.5%, P0.067) but increases in total stroke (2.9% versus 1.3%, P0.026) and intracranial hemorrhage (2.20% versus 0.97%, P0.047). The increase in intracranial hemorrhage was seen in patients 75 years of age.
Conclusions—Prehospital fibrinolysis allows 53% of patients to receive reperfusion treatment within 2 hours after symptom onset. The combination of tenecteplase with ENOX reduces early ischemic events, but lower doses of ENOX need to be tested in elderly patients. At present, therefore, tenecteplase and UFH are recommended as the routine pharmacological reperfusion treatment in the prehospital setting.
ENTIRE-TIMI 23
Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction
Background—ENTIRE-TIMI 23 evaluated enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab.
Methods and Results—Patients (n483) with ST-elevation MI presenting 6 hours from symptom onset were randomized to full-dose TNK and either unfractionated heparin (UFH) (bolus 60 U/kg; infusion 12 U/kg per hour) or enoxaparin (1.0 mg/kg subcutaneously every 12 hoursinitial 30 mg intravenous bolus), or half-dose TNK plus abciximab and either UFH (bolus 40 U/kg; infusion 7 U/kg per hour) or enoxaparin (0.3 to 0.75 mg/kg subcutaneously every 12 hoursinitial intravenous bolus of 30 mg). With full-dose TNK and UFH, the rate of TIMI 3 flow at 60 minutes was 52% and was 48% to 51% with enoxaparin. Using combination therapy, the rate of TIMI 3 flow was 48% with UFH and 47% to 58% with enoxaparin. The rate of TIMI 3 flow among all UFH patients was 50% and was 51% among enoxaparin patients. Through 30 days, death/recurrent MI occurred in the full-dose TNK group in 15.9% of patients with UFH and 4.4% with enoxaparin (P0.005). In the combination therapy group, the rates were 6.5% with UFH and 5.5% with enoxaparin. The rate of major hemorrhage with full-dose TNK was 2.4% with UFH and 1.9% with enoxaparin; with combination therapy, it was 5.2% using UFH and 8.5% with enoxaparin.
Conclusions—Enoxaparin is associated with similar TIMI 3 flow rates as UFH at an early time point while exhibiting advantages over UFH with respect to ischemic events through 30 days. These findings with enoxaparin are achieved with a similar risk of major hemorrhage.
Enoxaparin is superior to unfractionated heparin in patients with ST elevation myocardial infarction undergoing fibrinolysis regardless of the choice of lytic: an ExTRACT-TIMI 25 analysis
Aims We compared outcomes of ST-elevation myocardial infarction (STEMI) patients randomized to a strategy of either enoxaparin or unfractionated heparin (UFH) to support fibrinolysis.
Methods and results In the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction Study 25 (ExTRACT-TIMI 25) trial, 20 479 patients under- going fibrinolysis for STEMI with a fibrin-specific agent (N 1⁄4 16 283) or streptokinase (SK) (N 1⁄4 4139) were randomized to enoxaparin throughout their hospitalization or UFH for at least 48 h. The primary end point of death or nonfatal recurrent MI through 30 days occurred in 12.0% of patients in the UFH and 9.8% in the enoxaparin groups when treated with fibrin-specific lytics [odds ratioadjusted (ORadj) 0.78; 95% CI 0.70– 0.87; P , 0.001] and 11.8 vs. 10.2%, respectively, when treated with SK (ORadj 0.83; 95% CI 0.66–1.04; P 1⁄4 0.10; Pinteraction 1⁄4 0.58). Major bleeding rates including intracranial hemorrhage within the fibrin- specific cohort were 1.2 and 2.0% in the UFH and enoxaparin groups, respectively (P , 0.001) and 2.0% in UFH and 2.4% in enoxaparin patients in the SK cohort (P 1⁄4 0.16). Interaction tests between antithrom- bin- and lytic-type were non-significant (P 1⁄4 0.20). Death, nonfatal MI, or major bleeding was significantly reduced with enoxaparin in the fibrin-specific cohort (ORadj 0.82; 95% CI 0.74–0.91; P , 0.001) and favoured enoxaparin in the SK cohort (ORadj 0.89; 95% CI 0.72–1.10; P 1⁄4 0.29; Pinteraction 1⁄4 0.53).
Conclusion The benefits of an enoxaparin strategy over UFH were observed in both SK and fibrin-specific- treated STEMI patients. Therefore, an enoxaparin strategy is preferred over UFH to support fibrinolysis for STEMI regardless of lytic agent.
COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial)
Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial
Background Despite improvements in the emergency treatment of myocardial infarction (MI), early mortality and morbidity remain high. The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation, but its effects in patients with ST-elevation MI were unclear.
Methods 45 852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated clopidogrel 75 mg daily (n=22 961) or matching placebo (n=22 891) in addition to aspirin 162 mg daily. 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 93% of patients completed it. The two prespecified co-primary outcomes were: (1) the composite of death, reinfarction, or stroke; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This trial is registered with ClinicalTrials.gov, number NCT00222573.
Findings Allocation to clopidogrel produced a highly significant 9% (95% CI 3–14) proportional reduction in death, reinfarction, or stroke (2121 [9·2%] clopidogrel vs 2310 [10·1%] placebo; p=0·002), corresponding to nine (SE 3) fewer events per 1000 patients treated for about 2 weeks. There was also a significant 7% (1–13) proportional reduction in any death (1726 [7·5%] vs 1845 [8·1%]; p=0·03). These effects on death, reinfarction, and stroke seemed consistent across a wide range of patients and independent of other treatments being used. Considering all fatal, transfused, or cerebral bleeds together, no significant excess risk was noted with clopidogrel, either overall (134 [0·58%] vs 125 [0·55%]; p=0·59), or in patients aged older than 70 years or in those given fibrinolytic therapy.
Interpretation In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events in hospital, and should be considered routinely.
CLARITY–TIMI 28 Investigators
Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation
Background
A substantial proportion of patients receiving fibrinolytic therapy for myocardial in- farction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death.
methods
We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel (300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were scheduled to undergo angiography 48 to 192 hours after the st art of study medication. The primary efficacy endpoint was a composite of an occluded infarct-related artery (defined by a Thrombolysis in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography.
results
The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 per-centage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds of the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P = 0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups.
Conclusions
In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.
RIKS-HIA
Pre-hospital thrombolysis delivered by paramedics is associated with reduced time delay and mortality in ambulance-transported real-life patients with ST-elevation myocardial infarction
Aims There are sparse data on the impact of pre-hospital thrombolysis (PHT) in real-life patients. We therefore evaluated treatment delays and outcome in a large cohort of ambulance-transported real-life patients with ST-elevation myocardial infarction (STEMI) according to PHT delivered by paramedics or in-hospital thrombolysis.
Methods and results Prospective cohort study used data from the Swedish Register of Cardiac intensive care on patients admitted to the coronary care units of 75 Swedish hospitals in 2001–2004. Ambulance- transported thrombolytic-treated patients younger than age 80 with a diagnosis of acute myocardial infarction were included. Patients with PHT (n 1⁄4 1690) were younger, had a lower prevalence of co-morbid conditions, fewer complications, and a higher ejection fraction (EF) than in-hospital-treated patients (n 1⁄4 3685). Median time from symptom onset to treatment was 113 min for PHT and 165 min for in-hospital thrombolysis. One-year mortality was 7.2 vs. 11.8% for PHT and in-hospital thrombolysis, respectively. In a multivariable analysis, after adjusting for baseline characteristics and rescue angio- plasty, PHT was associated with lower 1-year mortality (odds ratio 0.71, 0.55– 0.92, P 1⁄4 0.008). Conclusion When compared with regular in-hospital thrombolysis, pre-hospital diagnosis and thrombo- lysis with trained paramedics in the ambulances are associated with reduced time to thrombolysis by almost 1 h and reduced adjusted 1-year mortality by 30% in real-life STEMI patients.
CAPTIM
Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study
Background Although both prehospital fibrinolysis and primary angioplasty provide a clinical benefit over in-hospital fibrinolysis in acute myocardial infarction, they have not been directly compared. Our aim was to find out whether primary angioplasty was better than prehospital fibrinolysis.
Methods We did a randomised multicentre trial of 840 patients (of 1200 planned) who presented within 6 h of acute myocardial infarction with ST-segment elevation, initially managed by mobile emergency-care units. We assigned patients to prehospital fibrinolysis (n=419) with accelerated alteplase or primary angioplasty (n=421), and transferred all to a centre with access to emergency angioplasty. Our primary endpoint was a composite of death, non-fatal reinfarction, and non-fatal disabling stroke at 30 days. Analyses were by intention to treat.
Findings The median delay between onset of symptoms and treatment was 130 min in the prehospital-fibrinolysis group and 190 min (time to first balloon inflation) in the primary-angioplasty group. Rescue angioplasty was done in 26% of the patients in the fibrinolysis group. The rate of the primary endpoint was 8·2% (34 patients) in the prehospital-fibrinolysis group and 6·2% (26 patients) in the primary-angioplasty group (risk difference 1·96, 95% CI –1·53 to 5·46). 16 (3·8%) patients assigned prehospital fibrinolysis and 20 (4·8%) assigned primary angioplasty died (p=0·61).
Interpretation A strategy of primary angioplasty was not better than a strategy of prehospital fibrinolysis (with transfer to an interventional facility for possible rescue angioplasty) in patients presenting with early myocardial infarction.
HART II
Randomized Comparison of Enoxaparin, a Low-Molecular-Weight Heparin, With Unfractionated Heparin Adjunctive to Recombinant Tissue Plasminogen Activator Thrombolysis and Aspirin
Background—Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular- weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI.
Methods and Results—Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups.
Conclusions—Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.
The role of fondaparinux as an adjunct
to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial
Aims No antithrombotic therapy has been shown to reduce mortality when used with thrombolytics in acute myocardial
infarction (AMI). In the OASIS-6 trial, fondaparinux significantly reduced mortality and reinfarction without increasing
bleeding in 12 092 patients with acute ST elevation MI.
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Methods and results
We report the results of a subgroup analysis in the 5436 patients (45%) receiving thrombolytics. According to local
practice, 4415 patients did not have an indication for unfractionated heparin (stratum 1) and 1021 did (stratum 2).
Fondaparinux reduced the primary study outcome of death or MI at 30 days [Hazard ratio (HR) 0.79, 95% confidence
interval (CI) 0.68 – 0.92] with consistent reductions in both mortality (HR and CI) and reinfarction (HR and CI). There
was a non-significantly lower rate of stroke (HR 0.77, CI 0.48–1.25). The risk of severe bleeding was significantly
reduced (HR 0.62, CI 0.40–0.94), and thus the balance of benefit and risk (death, MI and severe haemorrhage)
was clearly reduced by fondaparinux (HR 0.77, 95% CI 0.67–0.90). Results were consistent in the two strata, by
the different types of thrombolytics and across various time intervals from symptom onset to treatment.
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Conclusion In STEMI patients treated with thrombolytic agents (predominantly streptokinase), fondaparinux significantly reduced the risk of death, re-MI and severe bleeds.
