Fluvastatin reduces the 4-year cardiac risk in patients with multivessel disease.

BACKGROUND: To evaluate the impact of the extent of coronary disease (single- or multivessel) and of fluvastatin treatment on the incidence of long-term cardiac atherosclerotic complications in the Lescol Intervention Prevention Study (LIPS). METHODS: A total of 1063 patients with single-vessel disease and 614 patients with multivessel disease were randomized to receive fluvastatin (40 mg bid) or placebo for at least 3 years following a first successful percutaneous coronary intervention. The incidence of cardiac atherosclerotic events (cardiac death, non-fatal myocardial infarction, and coronary re-interventions not related to restenosis) was evaluated. RESULTS: Patients with multivessel disease tended to be older and presented a higher prevalence of associated risk factors and cardiovascular antecedents. The presence of multivessel disease markedly increased the risk of cardiac atherosclerotic events compared with single-vessel disease among patients allocated to placebo (RR 1.67 [95% CI: 1.24-2.25]; p<0.001). In patients treated with fluvastatin, however, no significant differences in long-term outcomes were observed between patients with multivessel disease and patients single-vessel disease (RR 1.28 [95% CI: 0.90-1.81]; p=0.2). CONCLUSIONS: Multivessel coronary disease impaired the 4-year outcomes after percutaneous intervention. However, the hazardous effect of multivessel disease was significantly reduced by long-term fluvastatin treatment.

Beta blockade in neurocardiogenic dysfunction: results of a clinical study.

BACKGROUND: Few placebo-controlled studies with ß-blockers have been performed in patients suffering from neurocardiogenic syncope. METHODS: We investigated the efficacy of metoprolol in 26 patients with recurrent syncope, suspected to be of neurocardiogenic origin, and positive tilt table test (TTT) outcome in a single-centre, double-blind, placebo-controlled, crossover study, with treatment periods of two weeks. Therapeutic efficacy was defined as a negative TTT after metoprolol and a positive TTT after placebo. Therapeutic failure was defined as a positive TTT after metoprolol and a positive or negative TTT after placebo. Patients with a negative TTT test after both metoprolol and placebo comprised the third group. RESULTS: The 24 patients who completed the study consisted of 14 females and 10 males, mean age 53 years, range 18-75 years. Therapeutic efficacy was observed in nine patients, therapeutic failure in eight patients and seven patients had a negative TTT after both placebo and metoprolol. According to the exact binomial test for paired proportions, the 95% confidence interval is 12 to 38% and p<0.01 in favour of treatment with metoprolol. CONCLUSION: These findings indicate a favourable effect of metoprolol.

Removal of thrombus from aortocoronary bypass grafts and coronary arteries using the 6Fr Hydrolyser.

This study evaluates the feasibility and safety of a 6Fr hydrodynamic thrombectomy catheter, the Hydrolyser, in native coronary arteries and aortocoronary bypass grafts. With use of a conventional contrast injector, saline solution is injected into the narrow lumen of the catheter which makes a 180 degrees bend at the tip. The resultant high-velocity jet (150 km/hour) is directed over a sidehole near the tip into a wide exhaust lumen. As a consequence of the Venturi effect, thrombus is sucked into that sidehole, fragmented, and removed through the wide exhaust lumen into a collection bag. Thirty-one thrombotic lesions were treated in 31 patients. The culprit vessel was a venous graft in 21 patients (15 with Thrombolysis in Myocardial Infarction Trial [TIMI] grade 0 or 1 flow) and a coronary artery in 11 patients (9 with grade 0 or 1 flow). Twenty-six patients had angina New York Heart Association functional class III or IV heart failure and 5 an acute myocardial infarction. In 26 patients, Hydrolyser therapy was the primary treatment, whereas in 5 patients coronary angioplasty preceded Hydrolyser therapy. In 1 patient the Hydrolyser could not reach the lesion. Thrombus was removed in 29 of the 31 patients. Successful reperfusion (TIMI grade 2 or 3 flow) by Hydrolyser therapy alone was achieved in 14 of the 24 patients with TIMI grade 0 or 1 flow before the procedure. Adjunctive therapy (coronary angioplasty, stent, or thrombolysis) was performed in 28 of the 31 patients. At the end of the total procedure 24 patients had TIMI grade 3 flow. Distal embolization during thrombectomy occurred in 2 patients, which led to a non-Q-wave infarction in 1. No patient died or needed emergency coronary bypass due to the Hydrolyser procedure. Thus, thrombectomy using the 6Fr Hydrolyser is feasible and was performed safely in 31 patients.

A new thrombosuction catheter for coronary use: initial results with clinical and angiographic follow-up in seven patients.

The presence of thrombus in a coronary vessel during percutaneous revascularisation can prevent adequate restoration of flow; it is also associated with an increased risk of distal embolization. We report the acute results and longer-term outcome of seven patients who underwent treatment with a new hydrodynamic thrombectomy catheter (Hydrolyser), designed for the rapid removal of acute, non-organised thrombus from coronary vessels. Three patients demonstrated total thrombotic occlusion of a coronary saphenous vein bypass graft (SVBG), whereas in four patients thrombus was present in a native coronary artery (NCA). In all seven patients, Hydrolyser thrombectomy resulted in removal of thrombus and restoration of flow through the occluded segment. Adjunctive balloon angioplasty or stent placement to treat residual stenosis was performed in five of the patients. Distal embolization of a free-floating thrombus mass occurred in one patient, without clinical sequelae. There were no procedure-related complications in any of the patients. One patient with a degenerated SVBG reoccluded after five days. The other six patients underwent angiographic follow-up after an interval of 3 to 8 months: A wide patent coronary artery, without restenosis, was seen in three of these patients, and the other three patients (two with treatment of an SVBG) underwent re-PTCA for restenosis. These data suggest that the Hydrolyser procedure, as reported in our experience, is safe and effective for the removal of acute thrombus in selected patients.

A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. Helvetica Investigators.

BACKGROUND: The likelihood of restenosis is a major limitation of coronary angioplasty. We studied whether hirudin, a highly selective inhibitor of thrombin with irreversible effects, would prevent restenosis after angioplasty. We compared two regimens of recombinant hirudin with heparin. METHODS: We randomly assigned 1141 patients with unstable angina who were scheduled for angioplasty to receive one of three treatments: (1) a bolus dose of 10,000 IU of heparin followed by an intravenous infusion of heparin for 24 hours and subcutaneous placebo twice daily for three days (382 patients), (2) a bolus dose of 40 mg of hirudin followed by an intravenous infusion of hirudin for 24 hours and subcutaneous placebo twice daily for three days (381 patients), or (3) the same hirudin regimen except that 40 mg of hirudin was given subcutaneously instead of placebo twice daily for three days (378 patients). The primary end point was event-free survival at seven months. Other end points were early cardiac events (within 96 hours), bleeding and other complications of the study treatment, and angiographic measurements of coronary diameter at six months of follow-up. RESULTS: At seven months, event-free survival was 67.3 percent in the group receiving heparin, 63.5 percent in the group receiving intravenous hirudin, and 68.0 percent in the group receiving both intravenous and subcutaneous hirudin (P = 0.61). However, the administration of hirudin was associated with a significant reduction in early cardiac events, which occurred in 11.0, 7.9, and 5.6 percent of patients in the respective groups (combined relative risk with hirudin, 0.61; 95 percent confidence interval, 0.41 to 0.90; P = 0.023). The mean minimal luminal diameters in the respective groups on follow-up angiography at six months were 1.54, 1.47, and 1.56 mm (P = 0.08). CONCLUSIONS: Although significantly fewer early cardiac events occurred with hirudin than with heparin, hirudin had no apparent benefit with longer-term follow-up.

Angiographic dose-finding study with r-hirudin (HBW 023) for the improvement of thrombolytic therapy with streptokinase (HIT-SK). Interim results.

To evaluate the efficacy and safety of hirudin, a direct thrombin inhibitor, in patients with acute myocardial infarction, a dose-finding, angiography study was carried out. After a pilot phase in 10 patients treated with a bolus of 0.1 mg.kg-1 and a continuous infusion of 0.06 mg.kg-1.h-1 (dose group I), two doses of hirudin, bolus 0.2 mg.kg-1.h-1 (DG II), and bolus 0.4 mg.kg-1 with 0.15 mg.kg-1.h-1 (DG III) were tested and compared with heparin as an adjunct to streptokinase and aspirin. This interim analysis was mandatory due to puncture-site related bleedings. Early and complete patency was achieved in 30% of 35 heparin patients, in 40% of 10 DG I, in 47% of 58 DG II and in 62% of 14 DG III patients. A dose-response relationship particularly between DG I and DG II, was also observed in the anti-thrombotic activity monitored by the aPTT. Apart from the catheter-related bleedings, there were low rates of serious adverse events.

Usefulness of repeat coronary angiography 24 hours after successful balloon angioplasty to evaluate early luminal deterioration and facilitate quantitative analysis.

Because of the unavoidable occurrence of vessel disruption after successful coronary balloon angioplasty, the reliability of quantitative angiographic analysis in that setting has been questioned. For this reason and the suggested occurrence of delayed elastic recoil, repeat angiography at 24 hours has been advocated in clinical interventional trials. In this study, these issues are confronted by performing comprehensive quantitative analysis (Cardiovascular Angiographic Analysis System) of coronary angiograms, acquired in multiple identical projections immediately after and 24 hours after angioplasty, in 102 patients with 110 successfully dilated lesions. Vasomotion was controlled by intracoronary nitrate before angiography and all patients were fully anticoagulated (activated partial thromboplastin time 85 to 120 seconds) for > 24 hours. Paired Student's t tests applied to angiographic measurements revealed that there was no significant deterioration in minimal luminal diameter or cross-sectional area from immediately after angioplasty to 24 hours later. It can thus be inferred that there is no phenomenon of delayed elastic recoil, at least during this time period. Measurement accuracy and precision of the Cardiovascular Angiographic Analysis System from the postangioplasty angiogram are highly acceptable, at < 0.01 and +/- 0.20 mm, respectively. Therefore, it is concluded that routine repeat 24-hour angiography is not indicated after successful angioplasty. A highly significant increase (p < 0.001) in reference diameter (+0.11 +/- 0.18 mm) was responsible for the apparent increase in percent diameter stenosis (2.4 +/- 7%), a finding that demonstrates the potential for error by selective application of percent diameter stenosis measurements alone. Preferential use of absolute luminal measurements is thus strongly recommended for clinical trials with angiographic monitoring.

Safety and efficacy of recombinant hirudin (CGP 39 393) versus heparin in patients with stable angina undergoing coronary angioplasty.

BACKGROUND: Enhanced thrombin activity has been associated with acute and long-term complications following balloon angioplasty (percutaneous transluminal coronary angioplasty (PTCA). We evaluated, in a 2-to-1 randomized, double-blind trial, the effects of recombinant hirudin, CGP 39 393, relative to unfractionated sodium heparin on periprocedural events, bleeding, early angiographic outcome, and coagulation in 113 patients with stable angina undergoing PTCA. METHODS AND RESULTS: Prior to PTCA, 20 mg CGP 39 393 was administered as a bolus, followed by continuous infusion at a rate of 0.16 mg.kg-1 x h-1, or 10,000 IU sodium heparin was administered as a bolus and continued at a rate of 12 IU.kg-1 x h-1 for 24 hours. Infusion was adjusted to activated partial thromboplastin time (APTT) levels. ST segment was monitored for 24 hours, and angiograms were analyzed with quantitative technique (QCA). In 74 CGP 39 393- and 39 heparin-treated patients, 132 lesions were dilated. Myocardial infarction and/or emergency coronary bypass surgery occurred in 1 (1.4%) CGP 39 393 patient compared with 4 (10.3%) heparin patients (relative risk, 7.6; 95% confidence interval, 0.9, 65.6). At 24 hours, complete perfusion was present in 91% heparin and 100% CGP 39 393 patients. Significant ST segment displacement was found in 11% of heparin versus 4% of CGP 39 393 subjects. Bleeding occurred only at the puncture site in 4 CGP 39 393-treated patients. QCA did not reveal significant differences between the groups. APTT values were more often in the target range and more stable in CGP 39 393 patients. Levels of thrombin-antithrombin III complexes, prothrombin fragment F1+2, and fibrinopeptide A indicated that CGP 39 393 was an effective inhibitor of thrombin activity. CONCLUSIONS: CGP 39 393 can safely be administered to patients undergoing elective PTCA for stable anginal symptoms and may have a more favorable anticoagulant profile than heparin.

Progressive development of a left ventricular thrombus.

In a patient with ischemic heart disease and terminal left ventricular failure, echocardiographic techniques (single-crystal M-mode echocardiograms and bidimensional, linear, dynamically focussed multiscan recordings) allowed the detection and follow-up of a left ventricular thrombus, later documented at autopsy.