BACKGROUND Direct thrombin inhibitors are a new class of drugs that may offer a more effective and potentially simpler alternative to heparin. Hirulog is a synthetic peptide based on the leech-derived compound hirudin and, like hirudin, is a highly specific, direct inhibitor of free and clot-bound thrombin. METHODS AND RESULTS TIMI 7 was a randomized, double-blind study of Hirulog, given with 325 mg/d aspirin to 410 patients with unstable angina. Patients received a constant infusion of Hirulog for 72 hours at one of four doses: 0.02 (n = 160), 0.25 (n = 81), 0.5 (n = 88), and 1.0 (n = 81) mg.kg-1.h-1. The primary efficacy end point was "unsatisfactory outcome," defined as death, nonfatal myocardial infarction (MI), rapid clinical deterioration, or recurrent ischemic pain at rest with ECG changes by 72 hours. Unsatisfactory outcome was not different among the four dose groups: 8.1%, 6.2%, 11.4%, and 6.2% (P = NS). However, the secondary end point of death or nonfatal MI through hospital discharge occurred in 10.0% of patients treated with 0.02 mg.kg-1.h-1 compared with 3.2% of patients treated with the three higher doses of Hirulog (0.25, 0.5, and 1.0 mg.kg-1.h-1, P = .008). Only 2 of 410 patients (0.5%) experienced a major hemorrhage attributed to Hirulog. CONCLUSIONS The direct thrombin inhibitor Hirulog is a promising new antithrombotic agent that deserves further study. The results of TIMI 7 lend support to the use of an antithrombin agent with aspirin in patients with unstable angina.

Background Although coronary thrombosis plays a critical role in the pathogenesis of unstable angina and non-Q-wave myocardial infarction (NQMI), the effects of thrombolytic therapy in these disorders is not clear. Also, the role of routine early coronary arteriography followed by revascularization has not been established.Methods and Results Patients (n=1473) seen within 24 hours of ischemic chest discomfort at rest, considered to represent unstable angina or NQMI, were randomized using a 2x2 factorial design to compare (1) TPA versus placebo as initial therapy and (2) an early invasive strategy (early coronary arteriography followed by revascularization when the anatomy was suitable) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients were treated with bed rest, anti-ischemic medications, aspirin, and heparin. The primary end point for the TPA-placebo comparison (death, myocardial infarction, or failure of initial therapy at 6 weeks) occurred in 54.2% of the TPA-treated patients and 55.5% of the placebo-treated patients (P=NS). Fatal and nonfatal myocardial infarction after randomization (reinfarction in NQMI patients) occurred more frequently in TPA-treated patients (7.4%) than in placebo-treated patients (4.9%, P=.04, Kaplan-Meier estimate). Four intracranial hemorrhages occurred in the TPA-treated group versus none in the placebo-treated group (P=.06). The end point for the comparison of the two strategies (death, myocardial infarction, or an unsatisfactory symptom-limited exercise stress test at 6 weeks) occurred in 18.1% of patients assigned to the early conservative strategy and 16.2% of patients assigned to the early invasive strategy (P=NS). In the latter, the average length of initial hospitalization, incidence of rehospitalization within 6 weeks, and days of rehospitalization all were significantly lower.Conclusions In the overall trial, patients with unstable angina and NQMI were managed with low rates of mortality (2.4%) and myocardial infarction or reinfarction (6.3%) at the time of the 6-week visit. These results can be achieved using either an early conservative or early invasive strategy, the latter resulting in a reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs. The addition of a thrombolytic agent is not beneficial and may be harmful.

To determine predictors of acute coronary dissection after coronary angioplasty, we studied 170 consecutive patients who underwent arterial dilatations of 234 arteries. Coronary dissection occurred in 103 (44%) arteries. More dissections occurred in women [40/73 (55%) versus 63/161 (39%), p < 0.03] and in patients with long lesions [45/74 (61%) versus 56/158 (35%), p < 0.0005]. Balloon/arterial diameter ratio was higher in patients with dissection (1.1 +/- 0.2 versus 1.0 +/- 0.2, p < 0.02). Complications did not differ in patients with and without dissection except for non-Q wave myocardial infarctions which were more frequent in patients with coronary dissection [10/12 (83%) versus 2/12 (17%), p < 0.01]. Thus coronary dissection during angioplasty is relatively frequent. However, most dissections are not associated with complications. Balloon dilatation of lesions in female patients and in patients with long lesions are more likely to result in dissection.

Clinical and anatomic determinants of primary success of percutaneous transluminal coronary angioplasty were retrospectively evaluated in 299 patients. Successful angioplasty (residual stenosis < 50%) was achieved in 350 (94%) of 373 lesions. The success rate in patients chronically treated with aspirin was higher than that of patients not treated with aspirin (95% versus 86%, P < 0.03). An additional finding was that the success rate in patients referred for coronary angioplasty because of acute myocardial infarction or postinfarction angina was lower than that of those without these characteristics (89% versus 96%, P < 0.01). No other clinical features studied influenced the outcome of coronary angioplasty. The angiographic characteristics of the lesions did not differ between patients with successful or failed angioplasty except for the degree of stenosis prior to the procedure, being lower in patients with successful procedure (92.4 +/- 7.6% versus 97.3 +/- 3.1%), P < 0.002). Thus coronary angioplasty can be performed with a high rate of success. Long-term pretreatment with aspirin may have a beneficial effect.

Although a variety of coronary angioplasty balloon inflation protocols are employed, prior studies have not evaluated the relation of rate of inflation to the type and extent of arterial damage produced by angioplasty. We randomized 103 patients to either a gradual (gradual, incremental increase to peak inflation pressure) or rapid inflation protocol (rapid increase to peak inflation pressure). Fifty-one patients with 72 lesions underwent gradual and 52 patients with 73 lesions received rapid inflation protocols. There were no significant group differences with regard to age, sex, artery dilated, number of diseased vessels, presence of unstable angina and lesion morphological characteristics except for more lesions located on a bend in the gradual inflation group (p < 0.02). Although there was a tendency towards a higher success rate in patients with gradual inflation, the complete success rates were high in both groups (100% vs. 93%, p < 0.08). The dissection rate was higher in patients with rapid inflation (43/73 [59%] vs. 26/72 [36%], p < 0.01). The collective complication rate was higher in patients with rapid inflation (19% vs. 6%, p < 0.03). No deaths occurred in either group. Thus a gradual compared to rapid coronary angioplasty balloon inflation protocol reduces the frequency of dissection despite similar inflation pressure and balloon/vessel diameter ratio. Gradual inflations may reduce the frequency of procedure-related complications.

Catheterization and Cardiovascular DiagnosisVolume 25, Issue 1 p. 79-79 Letter to the Editor Coronary thrombosis Lamberto G. Bentivoglio MD, Lamberto G. Bentivoglio MD Philadelphia, PennsylvaniaSearch for more papers by this authorSheryl Kelsey PhD, Sheryl Kelsey PhD Philadelphia, PennsylvaniaSearch for more papers by this author Lamberto G. Bentivoglio MD, Lamberto G. Bentivoglio MD Philadelphia, PennsylvaniaSearch for more papers by this authorSheryl Kelsey PhD, Sheryl Kelsey PhD Philadelphia, PennsylvaniaSearch for more papers by this author First published: January 1992 https://doi.org/10.1002/ccd.1810250118AboutRelatedInformationPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessClose modalShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume25, Issue1January 1992Pages 79-79 SCAI Member Sign in RelatedInformation RecommendedLate coronary stent thrombosis: Early vs. late stent thrombosis in the stent eraFenwei Wang MD, George A. Stouffer MD, Sergio Waxman MD, Barry F. Uretsky MD, Catheterization and Cardiovascular InterventionsThrombosis and anticoagulation therapy in coronary ectasiaP. E. Perlman M.D., N. A. Ridgeway M.D., Clinical CardiologyTreatment of coronary stent thrombosis with rheolytic thrombectomy: Results from a multicenter experienceJose A. Silva MD, Christopher J. White MD, Stephen R. Ramee MD, Tyrone J. Collins MD, J. Stephen Jenkins MD, Kalon Ho MD, Donald S. Baim MD, Joseph P. Carrozza MD, Stephane Rinfret MD, Cindy M. Setum PhD, Jeffrey J. Popma MD, Richard E. Kuntz MD, Catheterization and Cardiovascular InterventionsLate coronary stent thrombosis associated with exercise testingGuido Parodi MD, David Antoniucci MD, Catheterization and Cardiovascular InterventionsCoronary spasm producing coronary thrombosis in a patient with acute myocardial infarctionH. Naito M.D., T. Yorozu M.D., Y. Matsuda M.D., M. Yamaguchi M.D., Y. Tanabe M.D., H. Nakashima M.D., R. Kusukawa M.D., Clinical Cardiology

To determine the success rate and the safety of percutaneous transluminal coronary angioplasty in smokers (group I) versus nonsmokers (group II), we studied 298 consecutive patients who underwent coronary angioplasty of 371 consecutive lesions. Of these patients, 164 (55%) were smokers and had angioplasty of 210 lesions (57%). The smokers were younger (P < 0.0001) and predominantly males (P < 0.01). In smokers, more long lesions and total occlusions were detected (P < 0.01, and P < 0.02, respectively). More coronary dissections (without obstructions) occurred in smokers during the angioplasty (P < 0.006). However, there was no difference between the groups in regard to major complications. The success rate was high and similar in both groups (94% and 93%, respectively). Thus, although there are typical characteristics of smokers and their lesions and a tendency to coronary dissection during angioplasty, percutaneous transluminal coronary angioplasty is as safe and successful in patients who smoke as in patients who do not smoke.

To determine the success rate and the safety of percutaneous transluminal coronary angioplasty in patients with unstable angina pectoris (group 1) versus stable angina (group 2), we studied 299 consecutive patients who underwent coronary angioplasty of 373 consecutive lesions. Of these patients, 149 had unstable angina pectoris and dilation of 188 arteries. The success rate was high and similar in both groups (95 and 93%, respectively). The groups did not differ in regard to the lesion characteristics, vessels and number of sites dilated except for an increase in the presence of thrombus in the unstable angina group (p < 0.03). Although there was a higher incidence of coronary thrombus and more acute myocardial infarction in group 1 the major complication rate did not differ from that of group 2 and was low in both of them (3 and 2%, respectively). No deaths occurred. Six patients (3 in each group) needed urgent coronary artery bypass grafting while 3 additional patients developed acute Q-wave myocardial infarction (all of them in group 1). Thus, percutaneous transluminal coronary angioplasty is a safe and successful procedure in patients with unstable angina as well as in patients with stable angina pectoris.

Intravenous thrombolytic therapy with streptokinase in the setting of acute MI has been shown to be effective in improving left ventricular function, limiting infarct size, and improving early mortality. The benefit of this therapy is greatest when administered within 3 hours and is of minimal benefit when given more than 6 hours from symptom onset. Newer second generation thrombolytic agents such as intravenous r-TPA have been shown to be more effective at establishing patency of acutely thrombosed coronary arteries. TPA treatment produces patency rates similar to those observed with intracoronary administration of streptokinase (65 to 75 per cent). This agent will probably become standard therapy for patients with acute MI. Unfortunately, there are significant problems with systemic thrombolytic therapy. The potential for bleeding complications contraindicates the use of this therapy in patients with recent cerebrovascular events, recent surgery, or other possible bleeding problems. Acute angioplasty of the infarct-related artery has been shown to be effective in restoring blood flow in 85 per cent of patients with acute MI. Preliminary studies have suggested that this therapy, when administered within 4 hours from symptom onset, improves global and regional left ventricular function to a greater degree than intracoronary streptokinase. Patients receiving acute PTCA as a primary reperfusion modality have a lower incidence of post-infarction angina and provokable ischemia by exercise testing. If facilities and skilled personnel are available to perform PTCA within 4 hours from symptom onset, this therapy remains an alternative revascularization modality in patients with acute infarction and contraindications to systemic thrombolytic therapy. However, the benefit of PTCA with regard to reduction in mortality when used in this manner is unproven. PTCA can also be used as an adjunctive therapy administered at some time following systemic thrombolytic therapy. Performing PTCA acutely offers the potential to restore blood flow in 90 per cent of the patients that initially fail thrombolytic therapy. However, despite the use of PTCA in this subgroup, benefits with regard to improved ventricular function and decreased mortality have yet to be conclusively demonstrated. Performing acute PTCA following systemic thrombolytic therapy also incurs a high incidence of bleeding complications. If initial thrombolytic therapy reestablishes vessel patency, similar improvements in ventricular function can be expected even if PTCA is deferred until clinically indicated by evidence of recurrent ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

The cardioprotective efficacy of coronary perfusion during angioplasty was evaluated. Forty-two patients underwent transcatheter infusion of oxygenated Fluosol DA, 20% emulsion (FDA-20), a perfluorocarbon oxygen transport fluid, into the distal coronary artery during balloon inflations. Left ventricular function was continuously monitored by two-dimensional echocardiography, and left ventricular ejection fraction was quantitatively analyzed from the video record by an area-length method with a validated computer algorithm. Each patient had multiple nonperfused and perfused balloon inflations lasting more than 45 seconds. Nineteen of the 42 patients also received control solutions of oxygenated Ringer's lactate and nonoxygenated FDA-20. The ejection fraction of nonperfused sequences fell from a baseline value of 57 +/- 15% to 36 +/- 14% at 45 seconds of inflation time (p less than 0.0005). Falls of similar magnitude were seen in the lactated Ringer's and nonoxygenated FDA-20 perfused balloon inflations. The ejection fraction fall was associated with a 54% rise in end-systolic volume (p less than 0.0005) and a 4% rise in end-diastolic volume (p = ns) compared to baseline. Inflations perfused with oxygenated FDA-20 showed a 45-second, left ventricular ejection fraction of 53 +/- 13% (p = ns compared to baseline), which was significantly greater (p less than 0.0001) than the 45-second ejection fraction of the nonperfused, or control solution perfused sequences. Results indicate that the profound fall in ejection fraction occurring during percutaneous transluminal coronary angioplasty can be ameliorated by distal coronary perfusion with an oxygenated perfluorocarbon emulsion.