Early Invasive Procedures Research Articles

Acute coronary syndromes: extending medical intervention for five days before proceeding to revascularization

Intensive medical therapy before percutaneous coronary intervention appears to improve results in patients with unstable angina and non–ST-segment elevation myocardial infarction (MI). In this review of treatment strategies for patients with acute coronary syndromes, an “aggressive conservative” approach based on that used in the FRagmin and Fast Revascularisation during InStability in Coronary artery disease (FRISC II) trial is recommended. In FRISC II, an early (but not emergent) invasive therapeutic procedure undertaken within 7 days of starting open-label dalteparin lowered the risk of death and MI in moderate- and high-risk patients and resulted in better and more rapid symptom relief and fewer hospital readmissions than the noninvasive approach. The early treatment period represents a critical juncture in the spectrum of care for patients with unstable angina and affords physicians the best opportunity to educate them about the importance of risk factor modification. Informed consent is also an important issue, particularly in the event of ad hoc coronary intervention. The optimal treatment plan must include considerations of length of hospitalization, medication requirements, and the potential for symptom recurrence or need for hospital readmission. Finally, tailoring therapy for individual patients and establishing appropriate timing of procedures will help ensure the best possible outcome.

Resolution of ST-segment elevation in acute myocardial infarction--early prognostic significance after thrombolytic therapy. Results from the COBALT trial.

In acute myocardial infarction, early identification of patients at a high mortality risk is important for planning further therapeutic strategies. Previous studies have demonstrated that the extent of early resolution of ST-segment elevation may represent a simple, quick and noninvasive assessment to identify high risk groups of patients. In a subgroup of the COBALT Study population (Continuous Infusion vs Double Bolus Administration of Alteplase), ST-segment elevation was measured before and 90 to 120 minutes after treatment with alteplase. The subgroup of n = 1,760 patients was not different from the total COBALT population of n = 7169 patients regarding most clinical parameters except Killip Class before treatment. However, the overall 30-day mortality differed significantly between the main study and the substudy (7.76% vs 3.52%; p < 0.001). Three groups of ST-segment resolution were defined: 1. complete resolution (resolution > or = 70%; 762 patients), 2. partial resolution (< 70% and > 30%; 491 patients), 3. no resolution (< 30%; 507 patients). Mortality rate at 30 days for complete, partial and no resolution of ST-segment elevation was 1.31%, 4.28% and 6.11%, respectively (p < 0.001). While this significant correlation between the extent of ST-segment resolution and mortality could be observed for inferior acute myocardial infarction, it could not be found in patients with anterior acute myocardial infarction. This in part may be due to a selection bias that leads to an extremely divergent mortality rate of anterior acute myocardial infarction in the main study and the substudy (10.1% vs 3.94%; p < 0.0001). Despite this limitation, resolution of ST-segment elevation in acute myocardial infarction after thrombolytic therapy allows to identify patients at a high mortality risk and may help to select patients for early invasive procedures such as PTCA. Patients with complete ST-segment resolution showed a particularly low mortality rate, irrespective of the alteplase regimen used (front-loaded alteplase vs double bolus alteplase).

Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study

<h2>Summary</h2><h3>Background</h3> In unstable coronary-artery disease early invasive procedures are common, despite lack of evidence for the superiority of this approach. We compared an early invasive with a non-invasive treatment strategy in unstable coronary-artery disease. <h3>Methods</h3> In a prospective randomised multicentre study, we randomly assigned 2457 patients in 58 Scandinavian hospitals (median age 66 years, 70% men) an early invasive or non-invasive treatment strategy with placebo-controlled long-term low-molecular-mass heparin (dalteparin) for 3 months. Coronary angiography was done within the first 7 days in 96% and 10%, and revascularisation within the first 10 days in 71% and 9% of patients in the invasive and non-invasive groups, respectively. We followed up patients for 6 months. Analysis was by intention to treat. <h3>Findings</h3> After 6 months there was a decrease in the composite endpoint of death or myocardial infarction of 9·4% in the invasive group, compared with 12·1% in the non-invasive group (risk ratio 0·78 [95% Cl 0·62–0·98], p=0·031). There was a significant decrease in myocardial infarction alone (7·8 <i>vs</i> 10·1%, 0·77 [0·60–0·99]; p=0·045) and non-significantly lower mortality (1·9 <i>vs</i> 2·9%, 0·65 [0·39–1·09]; p=0·10). Symptoms of angina and re-admission were halved by the invasive strategy. Results were independent of the randomised dalteparin treatment. The greatest advantages were seen in high-risk patients. <h3>Interpretation</h3> The early invasive approach should be the preferred strategy in most patients with unstable coronary-artery disease who have signs of ischaemia on electrocardiography or raised biochemical markers of myocardial damage.

Management strategies for a better outcome in unstable coronary artery disease.

Unstable coronary artery disease is a term encompassing both unstable angina and non-Q-wave (non-ST-segment elevation) myocardial infarction. Patients with these conditions are at risk of early progression to acute myocardial infarction and death. Thus, management of these conditions must aim to reduce long-term mortality and morbidity. Risk stratification is crucial for the identification of patients whose risk of early progression is high; they may require coronary angiography and (if suitable) either percutaneous transluminal coronary angioplasty or coronary artery bypass surgery. No single variable can accurately predict risk, but considerable data are emerging to show that biochemical markers of myocardial injury, such as troponin-T and troponin-I, are valuable in combination with electrocardiographic findings and clinical features. Routine early invasive procedures (coronary angiography with or without revascularization) have not yet been shown to have any significant advantage over conservative regimens for the majority of patients. Antiplatelet, anticoagulant, and anti-ischemic agents remain the mainstay of treatment in the acute phase. New agents, such as glycoprotein IIb/IIIa receptor inhibitors and low-molecular-weight heparins, as well as antithrombins and Factor Xa inhibitors add to the treatments currently available. Thrombolytic agents are contraindicated in the absence of ST-segment elevation. After clinical stabilization, ongoing assessment should include exercise testing for all patients who are able; other imaging techniques should be used for patients unable to exercise. A profile indicating a high risk of future events is an indication for elective angiography and consideration for revascularization.

Low-molecular-weight heparin during instability in coronary artery disease

Summary Background Intravenous heparin is at least as effective as aspirin in preventing new cardiac events after an episode of unstable coronary artery disease (CAD), though the benefits are short-lived. Low-molecular-weight heparin has similar antithrombotic properties but can be given subcutaneously and is therefore suitable for long-term treatment. We have investigated whether subcutaneous low-molecular-weight heparin, in addition to aspirin and antianginal drugs, is protective against new cardiac events in unstable CAD. Methods 1506 patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction) took part in a double-blind trial and were randomly assigned subcutaneous dalteparin (Fragmin; 120 IU per kg bodyweight [maximum 10 000 IU] twice daily for 6 days then 7500 IU once daily for the next 35-45 days) or placebo injections. The primary endpoint was the rate of death and new myocardial infarction during the first 6 days. Secondary endpoints were the rates of death and new myocardial infarction after 40 and 150 days, the frequency of revascularisation procedures and need for heparin infusion, and a composite endpoint. Findings During the first 6 days the rate of death and new myocardial infarction was lower in the dalteparin group than in the placebo group (13 [1·8%] vs 36 [4·8%]; risk ratio 0·37 [95% Cl 0·20-0·68]), as were the frequencies of need for intravenous heparin (28 [3·8%] vs 58 [7·7%]; 0·49 [0·32-0·75]) and need for revascularisation (3 [0·4%] vs 9 [1·2%]; 0·33 [0·10-1·10]). The composite endpoint (death, myocardial infarction, revascularisation, intravenous heparin) also showed a significant difference in favour of dalteparin (40 [5·4%] vs 78 [10·3%]; 0·52 [0·37-0·75]). At 40 days the differences in rates of death and myocardial infarction and the composite endpoint persisted, although subgroup analysis showed that the effect was confined to non-smokers (80% of sample). Survival analysis showed a risk of reactivation and reinfarction when the dose was decreased, more pronounced in smokers. 4-5 months after the end of treatment, there were no significant differences in the rates of death, new myocardial infarction, or revascularisation. The regimen was safe and compliance was adequate. Interpretation We recommend that treatment with a combination of dalteparin and aspirin for at least 6 days should be considered in patients with unstable CAD to reduce the risk of new cardiac events and to allow time for risk stratification and selection of a long-term treatment strategy. Long-term dalteparin treatment instead of or in addition to early invasive procedures warrants further assessment.

Safety of thrombolytic therapy in elderly patients with massive pulmonary embolism: A comparison with nonelderly patients

Objectives. The aim of the study was to prospectively estimate the safety of thrombolytic therapy in elderly patients with massive pulmonary embolism in comparison with that in nonelderly patients.Background. In massive pulmonary embolism, lysis of thrombi can be achieved faster with thrombolytic therapy than with conventional heparin therapy, but it is administered with great caution in elderly patients because the risk of bleeding is thought to be higher than in nonelderly patients. Yet, thrombolytic therapy might be of value in elderly patients also, in allowing potentially more rapid improvement than is achieved with conventional heparin therapy.Methods. Eighty-nine patients with massive pulmonary embolism defined as Miller score ≥ 17/34 underwent thrombolytic therapy without consideration of age if they had no contraindication for such treatment. Fifty-three patients were ≤ 70 years old (mean age ± SD 54 ± 15 years; range 18 to 70), and 36 patients were ≥ 71 years old (78 ± 5 years; range 71 to 88). Except for mean age, there were no significant differences between the two treatment groups, particularly in terms of clinical presentation, average Miller score and pulmonary artery pressure regimen. Thrombolytic therapy was administered in the form of streptokinase at a dose of 100,000 IU/h over 12 h, with an initial injection of 250,000 IU over 15 min. Heparin was introduced 12 h after initiation of thrombolytic therapy. Urokinase or tissue-type plasminogen activator was used only in case of contraindication to streptokinase.Results. The frequency of uncomplicated clinical course was the same in both treatment groups. Surgical embolectomy was necessary in three nonelderly patients (5.6%) and one elderly patient (2.7%). Changes in pulmonary pressure regimen and Miller score were identical in both groups. Three patients died during the in-hospital course: two nonelderly patients (3.7%) and one elderly patient (2.7%). Minor bleeding occurred in five nonelderly (9.4%) and five elderly (13.8%) patients (p = 0.74). Major bleeding was observed in three nonelderly (5.6%) and five elderly (13.8%) patients (p = 0.29). Bleeding subsequent to early invasive procedure accounted for six (75%) of eight patients with major bleeding: two nonelderly patients (one of whom died) and four elderly patients. No intracranial hemorrhage was observed. No predisposing factor for bleeding was identified, except the need for early vascular access for pulmonary angiography through the femoral approach or for percutaneous insertion of an intracaval device for partial interruption of the inferior vena cava.Conclusions. Thrombolytic therapy administered for massive pulmonary embolism in patients free of contraindication yields similar results and carries a similar risk for bleeding complications in elderly compared with nonelderly patients. Limiting early invasive procedures may result in less frequent major bleeding complications.

Thrombolytic Therapy in Acute Myocardial Infarction

Recombinant tissue-type plasminogen activator (rt-PA), streptokinase (SK), and anisoylated plasminogen-streptokinase activator complex (APSAC) have salutary effects on mortality when administered to patients with evolving acute myocardial infarction (MI). Studies suggest that intravenous rt-PA is more effective in reperfusing occluded infarct-related arteries than SK, and the results of ongoing studies directly comparing the influence of SK and rt-PA on mortality are awaited. The clinical role of agents such as APSAC, urokinase, and pro-urokinase, used alone or in combination, remains to be determined. It is evident that a variety of thrombolytic agents will be effective, and variables such as ease of administration, pharmacokinetics, fibrin specificity, effects on blood viscosity, and incidence of adverse effects need to be assessed to determine which agents are the most suitable for clinical use. There is an increased risk of bleeding at vascular puncture sites with all thrombolytic agents. Current indications for thrombolytic therapy include ischemic chest pain of at least 30 min duration that is unrelieved by nitroglycerin and is associated with ST-segment elevations of at least 0.1 mV in two contiguous electrocardiographic leads. Such therapy is usually reserved for patients less than 75 years old who are not at increased risk for bleeding and whose chest pain began less than 4-6 prior to treatment. Trials are under way to determine whether patients with shorter pain duration, transient ST-segment changes (ie, unstable angina patients), chest pain associated with ST-segment depressions or T-wave inversions (ie, non-Q-wave infarction patients), or patients whose pain began more than 4 to 6 h earlier will benefit from early thrombolytic therapy. Other factors such as patient age, the likelihood of the diagnosis of MI, and the estimated risk of bleeding should also be considered. The findings of available major randomized trials indicate that early invasive procedures are generally unnecessary and that meticulous care must be exercised in the selection and management of patients subjected to thrombolytic therapy.

Pulmonary infiltrates and adult acute leukaemia: empirical treatment and survival related to the extent of pulmonary radiological disease.

In a retrospective review of 141 consecutive adult patients with acute leukaemia there were 33 local and eight diffuse parenchymal pulmonary abnormalities noted on the first abnormal chest radiograph. Empirical treatment was given without any invasive diagnostic procedures. Twenty of the 41 patients (49%) with radiographic abnormalities died--10 of 31 patients (32%) in the "local" group (excluding two who were not actively treated) and all eight patients in the "diffuse" group. One patient in the local group and six in the diffuse group died within 48 hours of the first abnormal chest radiograph. The results in the local group suggest that failure to respond to the initial treatment prescribed would allow time to perform an invasive procedure in most patients that may lead to a change in management. In the diffuse group, however, an early invasive procedure would be required if the result were to have a chance to influence the outcome.