Medical decision making in the choice of a thrombolytic agent for acute myocardial infarction. Quebec Acute Coronary Care Working Group.

Little is known about how physicians make decisions when the evidence is incomplete or controversial. While thrombolysis improves survival following acute myocardial infarction (AMI), conflicting evidence exists as to any specific agent's superiority, particularly if cost-effectiveness is considered. Using a Bayesian hierarchical model, the authors examined the patient, physician, and hospital characteristics that are related to the decision-making process concerning the choice of thrombolytic agent in a prospective registry of 1,165 AMI patients receiving thrombolysis. Tissue plasminogen activator (t-PA) was administered to 432 patients (31.8%) and streptokinase (SK) to the remainder. The presence of an anterior infarction, a previous myocardial infarction, low blood pressure, a cardiologist decision maker, younger age, and receiving treatment within six hours after the start of symptoms were independent predictors of receiving t-PA. The levels of importance that physicians accorded to these patient characteristics differed according to their practicing institutions. Generally, they followed evidence-based medicine and reasonably targeted high-risk patients to receive the more expensive t-PA. However, they also preferentially treated younger patients, where only a small absolute advantage appears to exist.     

Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release: results from the GUARDIAN trial

OBJECTIVES: We sought to determine if elevated cardiac serum biomarkers after coronary artery bypass graft surgery (CABG) are associated with increased medium-term mortality and to identify patients that may benefit from better postoperative myocardial protection. BACKGROUND: The relationship between the magnitude of cardiac serum protein elevation and subsequent mortality after CABG is not well defined, partly because of the lack of large, prospectively studied patient cohorts in whom postoperative elevations of cardiac serum markers have been correlated to medium- and long-term mortality. METHODS: The GUARD during Ischemia Against Necrosis (GUARDIAN) study enrolled 2,918 patients assigned to the entry category of CABG and considered as high risk for myocardial necrosis. Creatine kinase-myocardial band (CK-MB) isoenzyme measurements were obtained at baseline and at 8, 12, 16 and 24 h after CABG. RESULTS: The unadjusted six-month mortality rates were 3.4%, 5.8%, 7.8% and 20.2% for patients with a postoperative peak CK-MB ratio (peak CK-MB value/upper limits of normal [ULN] for laboratory test) of < 5, > or = 5 to <10, > or =10 to < 20 and > or =20 ULN, respectively (p < 0.0001). The relationship remained statistically significant after adjustment for ejection fraction, congestive heart failure, cerebrovascular disease, peripheral vascular disease, cardiac arrhythmias and the method of cardioplegia delivery. Receiver operating characteristic curve analysis revealed an area under the curve of 0.648 (p < 0.001); the optimal cut-point to predict six-month mortality ranged from 5 to 10 ULN. CONCLUSIONS: Progressive elevation of the CK-MB ratio in clinically high-risk patients is associated with significant elevations of medium-term mortality after CABG. Strategies to afford myocardial protection both during CABG and in the postoperative phase may serve to improve the clinical outcome.     

Recurrence of prinzmetal angina seven years following aortocoronary bypass surgery: A clinical and angiographic follow-up

A patient with Prinzmetal angina and ST segment elevation in the anterior ECG leads became asymptomatic after a 50% left anterior descending coronary artery stenosis was bypassed. However, seven years later Prinzmetal angina recurred but with ST segment elevation in the inferior ECG leads. Although the coronary bypass graft had remained patent, the proximal and distal left anterior descending coronary artery was occluded. No significant stenosis was present in the right coronary artery. Perhexiline maleate controlled his symptoms but when the drug was stopped because of side effects an acute inferior myocardial infarction occurred.     

An integrated clinical approach to predicting the benefit of tirofiban in non-ST elevation acute coronary syndromes. Application of the TIMI Risk Score for UA/NSTEMI in PRISM-PLUS.

AIMS: We evaluated the TIMI Risk Score for Unstable Angina and Non-ST Elevation Myocardial Infarction for predicting clinical outcomes and the efficacy of tirofiban in non-ST elevation acute coronary syndromes. METHODS AND RESULTS: Developed in TIMI 11B, the risk score is calculated as the sum of seven presenting characteristics (age > or =65 years, > or =3 cardiac risk factors, documented coronary disease, recent severe angina, ST deviation > or =0.5 mm, elevated cardiac markers, prior aspirin use). The risk score was validated in the PRISM-PLUS database (n=1915) and tested for interaction with the efficacy of tirofiban+heparin vs heparin alone. The risk score revealed an increasing gradient of risk for death, myocardial infarction or recurrent ischaemia at 14 days ranging from 7.7-30.5% (P<0.001). Dichotomized at the median, patients with a score > or =4 derived a greater relative risk reduction with tirofiban (P((Interaction))=0.025). Among patients with normal creatine kinase myocardial bands, the risk score showed a 3.5-fold gradient of risk (P<0.001) and identified a population that derived significant benefit from tirofiban (RR 0.73, P=0.027). CONCLUSION: The TIMI Risk Score is a simple clinical tool for risk assessment that may aid in the early identification of patients who should be considered for treatment with potent antiplatelet therapy.     

Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS)

The Cardiac Arrhythmia Pilot Study (CAPS) was a 1 year trial that analyzed the safety and effectiveness of arrhythmia suppression in 502 patients surviving acute myocardial infarction who had greater than or equal to 10 ventricular premature depolarizations/h or greater than or equal to 5 runs of ventricular tachycardia on a Holter recording obtained 6 to 60 days after the acute infarction. Because 100 of these patients received placebo in a double-blind fashion for 1 year, a comprehensive objective analysis was performed of spontaneous arrhythmia changes based on real data rather than statistical estimates. In the CAPS placebo group, 19% developed some serious clinical event in 1 year (death, heart failure, proarrhythmia) that could likely be attributable to antiarrhythmic drug toxicity. A significant reduction in the frequency of ventricular premature depolarizations (p = 0.004) occurred in the first few weeks of "therapy" with a further significant (p less than 0.04) decrease between 3 to 12 months. After initiation of placebo antiarrhythmic therapy, 27% had "apparent ventricular premature depolarization suppression" (greater than or equal to 70% reduction) after one Holter recording evaluation and nearly half (48%) after six Holter recordings to assess suppression were performed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ergonovine testing to detect spontaneous remissions of variant angina during long-term treatment with calcium antagonist drugs

A subgroup of 22 patients with variant angina who had responded well to calcium antagonist drugs were studied to determine if ergonovine testing could help assess the need for continued therapy. Before treatment all 22 patients exhibited angina with S-T elevation during ergonovine testing done in the coronary care unit according to a previously described protocol with sequential ergonovine doses of 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4 mg administered at 5 minute intervals. After 9.4 ± 4.7 (range 1 to 24) months of treatment (nifedipine 7 patients, diltiazem 3, verapamil 8, perhexiline 3, nifedipine and diltiazem 1), all patients were free from anginal attacks. Medication was discontinued and ergonovine testing repeated 24 to 48 hours later (3 weeks for perhexiline). In 12 of the 22 patiénts, angina or S-T segment shifts did not occur during the second ergonovine test to a maximal dose of 0.4 mg. Treatment was not restarted in these patients and all 12 remain free of variant anginal attacks 4.2 ± 2.9 (range 1 to 13) months later. In seven patients angina and S-T elevation occurred during the second ergonovine test, in the same electrocardiographic leads as during the test before treatment. In three patients the ergonovine test induced angina with S-T depression in the leads where S-T elevation had occurred during the previous test. Treatment was reinstituted in these 10 patients with a positive test. No complications resulted from ergonovine testing in any patient.We conclude that in many patients with variant angina, symptoms will disappear spontaneously and the ergonovine test will revert to negative. Treatment with calcium antagonist drugs can probably be safely discontinued in some patients with variant angina; ergonovine testing appears to be helpful in identifying such patients. Longer periods of follow-up are required to confirm that symptoms do not recur.     

Antiplatelet Therapy in Coronary Disease: What Agent to Use,When, and How?

The striking efficacy of aspirin in preventing the thrombotic complications associated with cardiovascular diseases has stimulated the development and clinical evaluation of a new antiplatelet therapy. Some of the new agents are less effective than aspirin and others are as effective, or slightly better in certain circumstances. Many new antiplatelet agents interfere with platelet function by mechanisms other than inhibition of cyclooxygenase. Selective inhibition of thromboxane synthase, and/or thromboxane receptor, and infusion of prostacyclin or analogues have not resulted in benefits superior to those of aspirin. Ticlopidine and clopidogrel provide an alternative pathway to inhibit platelet aggregation and are very effective drugs. The benefits derived from interventions targeting different pathways to platelet aggregation stress a potential for added benefits with combination of various drugs. Platelet aggregation can now be inhibited by occupying the GPIIb/IIIA receptor with pharmacological agents preventing part or all fibrinogen binding to the receptor. The use of abciximab, an antibody against the receptor, has resulted in a significant reduction of the acute complications associated with coronary angioplasty. The antibody is not specific against the receptor versus other synthetic peptidic and nonpeptidic compounds that have been developed, widening the spectrum of potential interventions. The antibody and the new agents are now being evaluated in unstable angina and myocardial infarction. Orally active inhibitors are also under development, extending the range of clinical investigation to secondary prevention of acute coronary syndromes. Other promising approaches include inhibition of platelets interaction with endothelium and with leukocytes, and inhibition of active platelet secretion products.