Acute myocardial infarction (AMI) remains
a major cause of mortality and morbidity in adult cardiology. It is well established fact that primary objective in treatment of AMI is early reperfusion.
After many clinical trials established that thrombolytic therapy for acute myocardial infarction preserves left ventricular function and reduces mortality, there is enough evidence that mechanical reperfusion therapy i.e. primary angioplasty is superior in reducing the rates of death, reinfarction, intracranial bleeding. To begin with it was an alternative to thrombolytic therapy (to avoid contraindications to its use and the risk of intracranial bleeding), primary percutaneous coronary intervention is now increasingly recognized as the reperfusion therapy of choice. The ability to restore brisk coronary flow in more than 90 per cent of patients and the positive relation between patency of the infarct-related artery at 90 minutes after the initiation of reperfusion therapy and in-hospital mortality rates lend credibility to the momentum behind primary percutaneous coronary intervention for patients with myocardial infarction associated with ST-segment elevation. Review of 23 randomized trials in which PAMI was compared with thrombolytic therapy showed that the former was superior in reducing the short-term rates of death (7 per cent, vs. 9 per cent with thrombolytic therapy; P < 0.001), nonfatal reinfarction (3 per cent vs. 7 per cent; P < 0.0001), stroke (1 per cent vs. 2 per cent; P = 0.0004), and the combined end point of death, nonfatal reinfarction, and stroke (8 per cent vs. 14 per cent; P < 0.001).
Nevertheless, thrombolytic therapy remains the corner stone of reperfusion treatment around the world because it is more widely available than PAMI. Even in the United States, the majority of hospitals do not have angioplasty capabilities, and in many that do, nearly 50 per cent of the patients with myocardial infarction associated with ST-segment elevation are treated with thrombolytic agents. The widespread unavailability of primary angioplasty appears to negate the superiority of this strategy as compared with thrombolysis. It also raises the obvious question of whether primary angioplasty performed after a patient is transferred to a facility where it is available will still be superior to thrombolytic therapy administered at the referral hospital. Given the inherent delay during transfer and the risks associated with transportation during acute myocardial infarction, the answer is not intuitive and still very compelling.
Five randomized trials have attempted to address this question. The Danish Multicentre Randomized Study on Thrombolytic Therapy versus PAMI in Acute Myocardial Infarction (DANAMI-2), is noteworthy for its randomized design, its practical approach to a critical question, and its careful consideration of the time between the onset of symptoms and reperfusion in its comparisons of strategies and treatment centres. Among patients at referral hospitals who were randomly assigned to be transferred to another centre for primary angioplasty or to receive thrombolytic therapy on site, the primary end point (a composite of death, reinfarction, or disabling stroke at 30 days) was reached in 8.5 per cent of the patients in the former group, as compared with 14.2 per cent of those in the thrombolytic-therapy group (P=0.002), and the difference was driven by a reduction in the rate of reinfarction in the angioplasty group (1.6 per cent, vs. 6.3 per cent in the thrombolytic-therapy group). Interestingly, 96 per cent of the patients were transferred from the referral hospital to an angioplasty centre within two hours after randomization. In fact, an analysis of all five trials that compared transfer for primary percutaneous coronary intervention with on-site thrombolytic therapy revealed that despite the delay necessary for the transfer (43 minutes on average), PAMI was associated with significant reductions in the rates of death, nonfatal reinfarction, and total stroke. Overall, untoward events during the transfer were insignificant with half per cent of mortality seen during transfer.
These provocative data raise the question of the importance of the time to reperfusion in patients undergoing primary angioplasty. Although the time dependency of catheter-based reperfusion may be less than that for thrombolytic therapy, particularly in the case of patients presenting more than three hours after the onset of symptoms, several studies have shown that the interval between arrival at the hospital and inflation of the balloon catheter and restoration of flow to the infarct-related artery (the “door-to-balloon time”) is directly related to in-hospital mortality. Indeed, a door-to-balloon time of less than 90 to 120 minutes has been associated with better survival.
Given the practical issues associated with transport of patients during acute myocardial infarction in our country, an integrated approach to reperfusion therapy is critically important. For patients with myocardial infarction associated with ST-segment elevation who present to hospitals without facilities for angioplasty within 3 hours after the onset of symptoms, thrombolytic therapy should be administered within 30 minutes of arrival (“door-to-needle time”). Transfer to a centre capable of performing angioplasty should be strongly considered when thrombolytic therapy is unsuccessful, contraindicated or when cardiogenic shock ensues, wherein the delay in transfer of the patient should be less than 60 minutes. Data available to date reveal that the two reperfusion strategies become equivalent with respect to death as the difference between the door-to-needle time and the door-to-balloon time approaches 60 minutes and with respect to the composite end point of death, reinfarction, or stroke after a delay of 90 minutes. Furthermore, both the comparison of Primary Angioplasty and Prehospital Thrombolysis in the Acute Phase of Myocardial Infarction (CAPTIM) trial and the PRAGUE-2 trial showed that primary percutaneous coronary intervention is superior to thrombolysis when the duration of symptoms is two to three hours or more but not when the duration of symptoms is less than two hours.
Nevertheless, now is the time for evidence-based therapy to dictate optimal patient care. Now is the time to discard the practice of transporting patients with acute myocardial infarction to the nearest hospital and to transport them preferentially to centres of excellence for primary percutaneous coronary intervention. This practice will foster the availability of highly experienced angioplasty teams that can perform primarypercutaneous coronary intervention with minimal delay. Moreover, now is the time for tertiary hospitals capable of performing primary angioplasty to offer it 24 hours a day, seven days a week.
Certainly, we need to continue to promote public education about the warning signs of heart attack and to promote the immediate activation of emergency medical systems when symptoms do occur (50 per cent of patients with acute myocardial infarction transport themselves to the hospital) in the effort to minimize the delay in the provision of treatment (with a goal of 30 minutes between the onset of symptoms and the start of reperfusion therapy). We also need to determine whether primary angioplasty performed immediately after arrival at angioplasty-treatment centres is superior to that performed after transfer from referral hospitals — a finding that might compel district hospitals that do not currently perform angioplasty procedures to begin to offer this reperfusion strategy. Clearly, we must continue to evaluate optimal pharmacologic and mechanical reperfusion strategies that may combine the advantages of both. Thrombolysis before hospital arrival and facilitated percutaneous coronary intervention (combination therapy with reduced-dose thrombolytic agents and glycoprotein IIb/IIIa platelet inhibitors before transfer for angioplasty) hold promise, although the latter strategy may be associated with a little increased risk of bleeding.
when available and performed by experienced operators at high-volume centres, primary percutaneous coronary intervention saves 20 lives and results in 60 fewer events for every 1000 patients treated. This suggests that primary percutaneous coronary intervention is indeed worth the wait. However, as in Denmark and the Czech we must strive to minimize the wait by implementing systems that allow rapid transfer between hospitals and that ultimately will allow direct transport from the home or other off-site location to the nearest centre of excellence for primary coronary angioplasty.
LOW MOLECULAR WEIGHT HEPARIN PREFERRED IN PALLIATIVE CARE
Palliative care inpatients at risk of thromboembolism find low molecular weight heparin more acceptable than wearing antiembolic stockings. In a qualitative study, Noble and colleagues interviewed 28 patients with advanced malignancy who were receiving low molecular weight heparin. Many of them thought that thromboprophylaxis had a positive effect on their quality of life and gave them a feeling of safety. Thromboprophylaxis guidelines are urgently needed for palliative care inapatient units and hospices, say the authors.
BMJ, 2006; 332 : 577.