Benefits and risks of thrombolysis for acute myocardial infarction

Thrombolytic therapy is a major step forward in the treatment of acute myocardial infarction and may result in up to 50% mortality reduction, provided that it is administered early (chapter 1). In 80 to 85% of patients with suspected acute myocardial infarction, a coronary artery is blocked by a clot. With thrombolytic therapy the closed coronary artery is desobstructed in may cases, is infarct size limited and left ventricular function preserved. Several thrombolytic agents are available for clinical use: streptokinase, APSAC, urokinase and more recently recombinant tissue-type plasminogen activator (rt-PA or alteplase). The latter is the genetically engineered natural occurring plasminogen activator. Which agent is superior is still a matter of debate. Unlike streptokinase, APSAC and urokinase, rt-PA dissolves blood clots without degradation of circulating fibrinogen during in vitro and in animal experiments, provided that the dose does not exceed a certain threshold. This property of rt-PA is called fibrin

Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarc

Tailored thrombolytic therapy. A perspective

BACKGROUND. In contrast with current standard regimens, it seems more appropriate to tailor thrombolytic therapy to individual patient characteristics. A proposed model for such tailored therapy is based on individual assessment of benefits and risks of thrombolytic therapy, taking into account the response of individual patients to the therapy given. METHODS AND RESULTS. Potential benefits of thrombolysis in individual patients can be predicted by use of demographic patient characteristics (age, sex, history of previous infarction) together with indicators of the ischemic area at risk (total ST segment deviation) and treatment delay. Using these parameters, the number of "lives saved" by thrombolytic therapy for specific patient characteristics can be estimated. Similarly, the risk of intracranial hemorrhage during thrombolytic therapy can be estimated from the patient's age, blood pressure at admission, and body weight. Depending on benefit/risk estimates, a choice can be made between regimens with high, medium, or modest thrombolytic efficacy. Continuous multilead ECG ischemia monitoring and rapid assays of myocardial proteins in serum can be used to assess the occurrence or absence of reperfusion and to detect signs of reocclusion. Such data help to decide whether thrombolytic therapy should be continued or intensified or might be discontinued in individual patients before the total standard dose has been administered. Such tailored reduction of the total thrombolytic dose will reduce the risk for bleeding complications in some of the patients. CONCLUSIONS. The concept of tailoring thrombolytic therapy and the models presented for benefit/risk assessment should be tested in clinical studies and may subsequently help the physician to select the optimal approach in individual patients

Trombolytische therapie van het acute hartinfarct

Trombolytische behandeling van het hartinfarct is één van de belangrijkste aanwinsten van de laatste jaren voor het therapeutisch arsenaal van de medicus practicus. Elders in dit tijdschrift worden de belangrijkste onderzoeksresultaten samengevat.1 De eerste onderzoekingen naar de baten van trombolyse bij het hartinfarct dateren van meer dan 20 jaar geleden. Doordat geen metingen van infarctgrootte of functie van de linker hartkamer werden verricht en de onderzoekingen steeds te klein waren om sterftereductie door trombolyse aan te kunnen tonen, konden er geen conclusies uit worden getrokken. Dit is wél mogelijk bij de onderzoekingen die gedurende de laatste jaren zijn uitgevoerd

Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris

Elevated plasma fibrinogen levels represent an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz. the acute phase reaction, total fibrin and fibrinogen degradation (TDP) levels and the fibrinogen G/A4 -gene polymorphism. The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study versus placebo. Functional plasma fibrinogen levels were measured with the Clauss assay and antigen levels with an enzyme immunoassay. C-reactive protein (CRP) and TOP levels were measured with an enzyme immuno assay. In the healthy volunteers the mean (SD) baseline level of functional plasma fibrinogen was 2.35 g/L (SD 0.35) and for fibrinogen antigen this was 2.49 g/L (SD 0.63). The geometrical mean (central 95% range) of CRP as 0.21 mg/L (0.02-2.36) and for TOP this was 0.18 ng/mL (0.03-1.00). After 4 weeks of ticlopidine administration, the functional fibrinogen levels had decreased with 0.20 g/L (9%, p=0.005 using the paired Student t-test) whereas the fibrinogen antigen levels, the CRP and the TOP levels had not significantly changed. In the stable angina pectoris patient the mean (SD) baseline levels of functional plasma fibrinogen were 3.44 g/L (SD 0.61) and of fibrinogen antigen they were 2.60 g/L (SD 0.49). The geometrical mean (central 95% range) of CRP was 1.45 mg/L (0.15-14.44) and for TOP this was 0.28 ng/mL (0.05-1.62). These baseline fibrinogen, CRP and TOP levels were significantly higher than in the volunteer group. After four weeks ticlopidine administration the functional fibrinogen levels had decreased with 0.39 g/L (11%, p<0.005), whereas the fibrinogen antigen, the CRP and the TDP levels had not significantly changed. The functional and antigen levels of fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen G/A~455 genotype. Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen β-gene polymorphisms. © Pearson Professional Ltd 1996

Assessment of the bradycardic and inotropic properties of ST 567 using a new scheme of administration

In 10 patients undergoing diagnostic cardiac catheterisation a bolus of 15 mg ST 567 was administered intravenously in 1.5 min followed by a 30 min infusion of 7.5 mg. The maximal plasma level was 343 +/- 131 ng ml-1 (mean +/- s.d.) 1 min after bolus injection and stabilised around 179 ng ml-1 thereafter. Heart rate decreased from 71 +/- 10 beats min-1 at baseline to 66 +/- 10 beats min-1 at the end of the bolus injection (-7%). This decrease in heart rate persisted during the whole observation period. Also there was an 8% reduction in peak positive first derivative of LV pressure. Cardiac output measured by thermodilution during atrial pacing decreased from 5.9 +/- 1.1 l min-1 to 5.3 +/- 0.7 l min-1 (P less than 0.02). In 3 patients with the largest decrease in cardiac output, the end diastolic LV pressure at the end of the observation period decreased, which may reflect a decrease in pre-load. Only in 1 patient the decrease in end diastolic LV pressure exceeded twice the standard deviation of the random error component of duplicate measurements. Thus, although normal therapeutic plasma levels were achieved, ST 567 demonstrated negative inotropic properties independent of changes in heart rate with this scheme of administration

Therapeutic reasoning: from hiatus to hypothetical model

Rationale Extensive research has been conducted on clinical reasoning to gain better understanding of this process. Clinical reasoning has been defined as the process of thinking critically about the diagnosis and patient management. However, most research has focused on the process of diagnostic reasoning. Because of the lack of understanding regarding therapeutic reasoning, education in patient management decisions lacks a solid theoretical basis. Aims and objective To improve medical education, training and refresher courses with regard to therapeutic decision making. Methods A search on the literature about clinical reasoning has been conducted. Based on this literature a hypothetical model of therapeutic reasoning is developed. Results It is assumed on the literature about diagnostic and therapeutic reasoning that after the diagnosis has been formulated, the process of determining the therapy is initiated by a concept called the therapy script. Patient cases unconsciously elicit such scripts and they consist of relevant treatments, knowledge and clinical experiences. Analytical and non-analytical processes determine the final choice of therapy. Subsequently, these processes adapt the therapy script continuously. Conclusions A hypothetical model of therapeutic reasoning has been developed in order to improve medical education, training and refresher courses with regard to therapeutic decision making. Future research should empirically test the validity of this hypothetical model in different phases of the medical education continuu