What is the relevance of the HOPE study in general practice?

The unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study strongly support extending the use of the angiotensin-converting enzyme (ACE) inhibitor ramipril as a preventive agent for patients at high risk of cardiovascular events with normal left ventricular function. In addition, ramipril provides significant benefit in diabetic patients. These findings will impact on how ramipril is used in primary care, where ACE inhibitors are currently underprescribed. Patients reflecting the inclusion criteria of the HOPE study should be considered as suitable candidates for long-term ramipril therapy as an addition to their existing drug regimen. Screening should include control of kidney function (by serum creatinine), particularly within the first two weeks of treatment, in addition to regular monitoring of serum potassium. However, the HOPE study shows that ramipril is well tolerated at high doses and over a long treatment period. The effectiveness of therapy should also be regularly reviewed and dose adjustments made where necessary. If concern remains, referral to a specialist--a cardiologist or a diabetologist--may ultimately be necessary.

Prospective use of glycoprotein IIb/IIIa receptor blockers in the emergency department setting.

Platelets play a pivotal role in the pathophysiology of acute coronary syndromes (ACS) and thus are logical therapeutic targets for treatment of this disease process. Platelet glycoprotein (GP) IIb/IIIa receptor antagonists, which interrupt the final common pathway of platelet aggregation, have been proved to reduce the 30-day incidence of death, acute myocardial infarction (MI), and urgent revascularization in both high-risk and low-risk patients undergoing percutaneous intervention procedures. Three-year follow-up has indicated that these benefits appear durable. Recent large-scale randomized trials have demonstrated the value of GP IIb/IIIa receptor inhibitors in reducing the risk of death and MI in patients with unstable angina or those with MI with non-Q-wave abnormalities who are receiving pharmacologic management. In addition, emerging evidence suggests a future role for GP IIb/IIIa receptor inhibitors as an adjunct to low-dose fibrinolytic therapy in patients with acute MI. As the list of indications for GP IIb/IIIa receptor antagonists expands to encompass the full spectrum of ACS, there is increasing interest in the potential use of these agents in the emergency department setting. The integration of GP IIb/IIIa receptor inhibitors into ED protocols will ultimately depend largely on whether these drugs prove to be safe and effective regardless of the direction of ST-segment deviation, and irrespective of whether definitive therapy will be invasive or conservative.

Prospective use of platelet glycoprotein IIb/IIIa receptor blockers in the emergency department setting.

Platelets play a pivotal role in the pathophysiology of acute coronary syndromes (ACS) and thus are logical therapeutic targets for treatment of this disease process. Platelet glycoprotein (GP IIb/IIIa receptor antagonists, which interrupt the final common pathway of platelet aggregation, have been proven to reduce the 30-day incidence of death, acute myocardial infarction (MI), and urgent revascularization in both high-risk and low-risk patients undergoing percutaneous intervention procedures. Three-year follow-up has indicated that these benefits appear durable. Recent large-scale randomized trials have demonstrated the value of GP IIb/IIIa receptor inhibitors in reducing the risk of death and MI in unstable angina/non-Q-wave MI patients receiving pharmacologic management. And, emerging evidence suggests a future role for GP IIb/IIIa receptor inhibitors as an adjunct to low-dose fibrinolytic therapy in patients with acute MI. As the list of indications for GP IIb/IIIa receptor antagonists expands to encompass the full spectrum of ACS, there is increasing interest in the potential use of these agents in the emergency department setting. The integration of GP IIb/IIIa receptor inhibitors into emergency department protocols will ultimately depend largely on whether these drugs prove to be safe and effective regardless of the direction of ST-segment deviation, and irrespective of whether definitive therapy will be invasive or conservative.

Pre-hospital thrombolysis, is it useful?

Thrombolytic treatment efficacy is greater when the delay between onset of pain and treatment is short. One way to shorten this delay is to give treatment at home, but one cannot recommend this technique if it has not been demonstrated first, that pre-hospital thrombolysis is feasible and safe, and second, that it is useful. We have been able to demonstrate that pre-hospital thrombolysis with APSAC is feasible and safe. Our findings are similar to those of other teams using other drugs. Whether pre-hospital thrombolysis is useful has not been adequately assessed; and we consider that first, the benefit of pre-hospital vs in-hospital thrombolysis must be determined, and second, the results of a study involving many centres, with various levels of training, practicing pre-hospital thrombolysis must be examined. Two large scale studies are currently being performed. One in Seattle, uses left ventricular ejection fraction as the major end-point, whereas the other, the European Myocardial Infarction Project, (EMIP) is using total mortality. Data currently available indicate that pre-hospital thrombolysis with APSAC is feasible, easy and safe. We hope that we will very soon be able to answer the last question: is it useful?

Prehospital use of APSAC: results of a placebo-controlled study.

Thrombolytic treatment efficacy is greater when the delay between onset of pain and treatment is short. To give treatment before admission to a coronary care unit, responsibility needs to be transferred from cardiologists to other physicians working in mobile care units. We conducted a 2-part feasibility study to investigate this strategy. Part 1 evaluated the diagnostic accuracy of mobile care unit physicians. Results from this study indicate that with regard to the diagnosis of acute myocardial infarction, the risk of a wrong diagnosis is low. Part 2 was a placebo-controlled trial involving 100 patients in which 57 received anisoylated plasminogen streptokinase activator complex (APSAC) (30 U) at home and 43 received placebo at home. Patients receiving placebo at home were reevaluated on arrival in a coronary care unit and received APSAC (30 U) if indicated. The main results were that (1) diagnostic accuracy was good--all patients had an acute coronary syndrome and 97 of 100 patients had myocardial infarction; (2) time gain was approximately 60 minutes; (3) coronary patency rate was 72%; (4) ejection fraction was higher in the prehospital group (56.7%) than in the control group (53.4%), but the difference was not significant; (5) there was no rhythmic or bleeding complication related to the prehospital treatment; (6) 5 patients died from cardiogenic shock--2 between home and hospital and 3 in the hospital (3 received thrombolytic treatment at home and 2 received placebo at home and APSAC in the hospital); and (7) prehospital administration of APSAC did not induce a delay in arrival to the coronary care unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Prehospital administration of anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

25 patients have been included in a randomised trial aimed to compare prehospital and hospital administration of anisoylated plasminogen streptokinase activator complex (AP-SAC). Patients were first seen, at home, by a noncardiologist doctor working in a mobile-care unit and were then evaluated for entry into the study. If they had evidence of myocardial infarction lasting for less than 3 hours and if there was no contraindication to thrombolytic therapy they were randomly allocated to APSAC 30U or placebo. They were next referred to an intensive coronary unit (ICU). On arrival in the ICU patients were reevaluated and received APSAC if they had previously received placebo. For 24 patients, diagnosis of myocardial infarction was confirmed. One patient died at home after having received placebo. There was 1 hospital death. At-home injection was made within a median of 124 minutes after the beginning of pain, whereas hospital administration was made after a median of 180 minutes. On a clinical basis reperfusion occurred in 16 out of 21 evaluable patients. Four patients had coronary artery bypass graft surgery and 9 had angioplasty. We conclude that prehospital administration of APSAC is feasible, well-tolerated and is a good way to shorten the delay of thrombolytic treatment in myocardial infarction.