The Sirolimus-eluting coronary stent in daily routine practice in Germany: trends in indications over the years. Results from the prospective multi-centre German Cypher Stent Registry.

BACKGROUND: Drugeluting coronary stents (DES) are increasingly used during percutaneous coronary interventions (PCI). Due to limited budgets in Germany, no special reimbursement has been given for their use and therefore they were mainly used in selected patients. METHODS: In order to determine the change in indications in patients treated with a Sirolimus-eluting stent (SES) in daily clinical practice between 2002 and 2005, we analysed data from a prospective multi-centre DES registry, the German Cypher Stent Registry. RESULTS: From April 2002 until September 2005, 11 507 patients at 132 hospitals, who received at least one SES during their PCI, were included. Between 2002 and 2005, the median age of patients increased from 63 years to 66 years (p for trend <0.0001), whereas the prevalence of prior coronary bypass surgery (p<0.0001) and prior PCI (p<0.001) significantly decreased. Initial presentation of patients was stable over time, with a small increase of patients treated for non-ST elevation myocardial infarction (p=0.05). We found a significant increase in the treatment of complex stenoses (p<0.0001) as well as an increase in the proportion of chronic total occlusions (p<0.01). There was a steady increase in the proportion of patients treated for de novo lesions (p<0.0001), which was accompanied by a relative decrease in the proportion of patients treated for in-stent restenosis (p<0.0001). Concerning interventional characteristics a significant increase in the length of SES implanted per lesion, the numbers of SES implanted per lesion as well as an increase of the proportion of patients treated for more than one stenosis during one intervention could be observed (all p<0.0001). There was a significant decrease in the use of glycoprotein II b/IIIa antagonists during the PCI (2002: 26.5 to 14.2% in 2005, p<0.0001). MACE rates until hospital discharge did not change significantly over time. CONCLUSIONS: Between 2002 and 2005 there were two trends in the use of SES: a) a significant increase in the use of SES for de novo lesions and b) a significant trend to use SES for longer lesions, smaller arteries, more complex lesions and more SES per lesion. In summary these findings indicate that still SES are mainly used in patients with lesions that are at high risk for restenosis.

[Predictive value of an ischemia test in men and women with stable angina pectoris in clinical practice. Results of the heart catheter registry of the Working Society of Senior Hospital Cardiologists]. / Prädiktiver Wert eines Ischämietests bei Männern und Frauen mit stabiler Angina pectoris im Klinikalltag. Ergebnisse des Herzkatheter-Registers der ALKK.

BACKGROUND AND OBJECTIVE: Symptoms of coronary artery disease (CAD) and the accuracy of non-invasive tests differ between men and women. This study sought to evaluate the difference between the predictive value of a stress test in clinical practice for the diagnosis of significant coronary heart disease (CHD: stenosis > 50%) between women and men with stable angina. PATIENTS AND METHODS: 143,848 consecutive patients undergoing diagnostic coronary angiography at 99 hospitals during 2002 were included in the prospective cardiac catheter registry of the Working Party of Senior Hospital Cardiologists (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte [ALKK]). All patients with stress test and stable angina CCS class I-III (n=27387; 20.4%) were included, 10,911 (39.8%) of them female. 70.6% of women and 73.2% of men had a positive stress test. RESULTS: In 46.1% of women and 71.5% of men with positive test and stable angina had relevant CHD (p<0,001). Diabetes increased the prevalence of CHD in patients with a positive test both in women (65.5%) and men (80.5%), with CCS class III angina to 63.3% and 85.8%, respectively. CONCLUSIONS: In clinical practice a positive stress test in women with stable angina is associated significantly less often with clinically relevant CHD than in men. The low positive predictive value of 46.1% underlines the need for additional clinical features like diabetes or cardiac symptoms (CCS class) before invasive diagnosis is performed.

Incications and complications of invasive diagnostic procedures and percutaneous coronary interventions in the year 2003. Results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

BACKGROUND: The ALKK registry contains about 20% of the invasive and interventional cardiological procedures performed in Germany. METHODS: In 2003 a total of 82,282 consecutive diagnostic invasive and 30,689 interventional procedures from 75 hospitals were centrally collected and analyzed. RESULTS: The main indication for an invasive diagnostic procedure was coronary artery disease in 92.5% of cases, myocardial disease in 1.6%, impaired left ventricular function in 4.0%, valve disease in 4% and other indications in 1.9%. An acute coronary syndrome was present in 25% of the patients. The rate of severe complications in patients with a lone diagnostic invasive procedure was low (<0.5%). The indication for percutaneous coronary intervention (n=30,689) was stable angina in 44.1%, ST elevation myocardial infarction in 22.3%, non ST elevation myocardial infarction in 14.8%, unstable angina in 10.0%, silent ischemia in 2.2%, prognostic in 5.2% of patients. The majority of interventions were performed directly after the diagnostic procedure (n=23,887=78.6%). The intervention was successful in 94.6% of cases. Stent implantation was performed in 77.2%, with 1 stent in 88.4%, two stents in 7.6% and 3 or more stents in 3.3%. A drug-eluting stent was implanted in 3.6% of the cases. The complication rate after PCI was influenced by the indication for the intervention. The in-hospital mortality in patients with cardiogenic shock was 33%, while in patients with stable angina, silent ischemia and prognostic indication only 0.2% died. CONCLUSION: There is an increase of invasive diagnostic and interventional procedures in patients with acute coronary syndromes, with 47% of PCIs performed in these patient. PCIs were performed in 75% of the cases directly after the diagnostic procedure. The rate of stent implantation seems to have reached a plateau at around 80%, while drug-eluting stents were implanted only in a minority of cases. The complication rate is mainly dependent on the clinical presentation of the patients and the indication for PCI.

Sirolimus-eluting stent treatment for isolated proximal left anterior descending artery stenoses. Results from the prospective multi-center German Cypher Registry.

BACKGROUND: Stenting of isolated proximal LAD stenoses is still a controversial issue since it is associated with higher target vessel revascularization (TVR) rate than both bypass surgery using the internal mammary artery, and stenting of other coronary artery territories. The sirolimus- eluting stent (SES) has been reported to significantly reduce restenosis rates in de novo coronary lesions. Therefore, we compared patients from the German Cypher Registry treated with SES for isolated proximal LAD lesions with those stented for isolated lesions in the proximal LCX or RCA. METHODS: A total of 349 patients treated with SES were analyzed. 249 patients were treated for proximal LAD stenosis, and 100 for proximal LCX/RCA stenoses. The combined clinical endpoint was MACCE (death of any cause, non-fatal MI and non-fatal stroke) and TVR at 6 months. RESULTS: In-hospital events (death, MI and TVR) did not differ significantly between both groups (3.2% for the LAD group vs 2.0% for the LCX/RCA-group, p=0.73). The combined end point of death of any cause, non-fatal MI and non-fatal stroke at six months was 2.6% in the LAD group, and 2.2% in the LCX/RCA group (p=1.0). TVR occurred in 4.8% of the LAD group and in 6.5% of the LCX/RCA group at six months (p=0.58). The percentage of patients free from angina at daily activities was 80.6% in the LAD group, and 77.4% in the LCX/ RCA group (p=0.52). CONCLUSION: SES once implanted into isolated proximal LAD stenoses appears as effective as reported in other vessel territories. Accordingly, stenting of the proximal LAD using SES might prove a suitable alternative to surgery.

"Real life" use of sirolimus-eluting coronary stents in Germany. Results from the prospective multi-centre German Cypher Registry.

BACKGROUND: Drugeluting stents (DES) are currently judged to be a "break-through" technology for the prevention of restenosis after percutaneous coronary interventions (PCI). However, experience is limited to randomised controlled clinical trials (RCT) in selected lesions and the currently available DES are more expensive compared to conventional "bare" stents. Therefore, actual clinical practice may be very different to RCT. METHODS: We analysed the data of the German Cypher trade mark Registry, a nationwide registry which was initiated in parallel to the launch of the first DES, the Cypher trade mark sirolimus-eluting coronary stent, in April 2002. RESULTS: From April 2002 until March 2003, 1638 procedures at 88 hospitals were included in the German Cypher trade mark Registry. The mean inclusion rate per centre and month remained low (<3 procedures/month and participating hospital) during the whole inclusion period. Most patients presented with stable angina pectoris (45.8%); however, 6.4% of patients were treated for a non-ST elevation myocardial infarction, 10.3% of patients for ST elevation myocardial infarction and 1.7% in cardiogenic shock. In patients without ST elevation myocardial infarction, a de novo stenosis was treated in 68.4% of cases, a restenosis in 4.1%, and an in-stent restenosis in 25.5% of cases. Chronic total occlusions were treated in 6.1% of patients. Predilatation was performed in 68.3% of patients and 1.05 +/- 0.35 Cypher trade mark stents were implanted per patient with a median (quartiles) stent length of 18 (13-21) mm. PCI-related death occurred in 0.1% of patients and a Q-wave myocardial infarction in 1.1%. Urgent re-PCI before hospital discharge was performed in 1.3% and urgent bypass surgery in 0.1% of cases. CONCLUSIONS: The use of the sirolimus-eluting coronary stents in this "real life" registry was found to be safe concerning acute complications. In about one half of the registry patients, the DES was implanted in lesions that were excluded from RCTs.

Percutaneous transluminal coronary angioplasty of left main stenosis--results of the German PTCA registry.

In cases with protected left main stenosis by previous bypass surgery or as an emergency intervention in patients presenting with acute myocardial infarction and cardiogenic shock, percutaneous transluminal coronary angioplasty is performed as an alternative treatment strategy to bypass surgery. A review of 262 left main angioplasties revealed a procedure-related mortality in cases without protection of the left main coronary artery of 9.1% (4/44), in cases with partially protected left main stenosis by collaterals to either left coronary artery of 4.8% (1/21) and 0.5% (1/187) in cases with nonobstructed bypass grafts to either left coronary artery. Coronary angioplasty of an unprotected left main coronary artery, had an unacceptably high procedure-related mortality rate and should therefore not be performed even in cases of emergency intervention. The risk stratification of the procedure can be evaluated by the proposed grading of left main artery protection.

Audit and quality control in angioplasty in Europe: procedural results of the AQUA Study 1997: assessment of 250 randomly selected coronary interventions performed in 25 centres of five European countries. AQUA Study Group, Nucleus Clinical Issues, Working Group Coronary Circulation, of the European Society of Cardiology.

AIMS: Percutaneous transluminal coronary angioplasty (PTCA) has become the most widely used major intervention in western medicine. However, there is disparate use of this technique among different European countries and the U.S.A. In an attempt at quality assurance, the working group Coronary Circulation of the European Society of Cardiology has carried out a study on appropriateness, necessity, and performance of PTCA in Europe. The present paper reports on the procedural results of this survey. METHODS: In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the From the countries participating in the European Registry of Coronary Intervention, the three countries with the highest absolute PTCA volume (Germany, France, and the United Kingdom) and two randomly selected countries (Belgium and Italy) were chosen for investigation. In these countries, five centres were selected at random according to the following criteria: one centre with >1000, three centres with 300-1000, and one centre with <300 procedures per year. In each of these, 10 cases from the first half of 1997 were randomly identified and all pertinent documentation was collected. RESULTS: In 250 cases, 325 stenoses were addressed as target lesions. Single vessel disease was present in 41%. History included stable angina in 49%, unstable angina in 32%, atypical chest pain in 6%, no anginal pain in 12%, and acute/subacute myocardial infarction in 13%. The percentage of patients with either positive stress test and/or unstable angina, acute/subacute infarction, previous infarction (within 6 months) or coronary revascularization amounted to 98%. Single vessel intervention accounted for 90%. In 41% balloon-only angioplasty was performed and in 54% at least one stent was implanted with considerable variation among countries. The use of other new devices amounted to only 3%. In 92%, the operators documented a successful procedure. Major complications (myocardial infarction, emergency bypass surgery, or death) were found in 4.8%. CONCLUSIONS: Based on scrutinized hospital and operator data, the present study revealed a satisfactorily high percentage of justifiable indications, an adequate procedural success rate, and an acceptably low complication rate. Further analysis by an expert panel will address appropriateness, necessity, and procedural performance of the individual cases.

[Deformation of a coronary stent as a sequela of resuscitation]. / Deformation eines koronaren Stents als Reanimationsfolge.

We report a case of LAD-stent deformation by extracorporeal cardiopulmonary resuscitation (CPR) shortly after stent implantation. To our knowledge, this is the first reported case. During an emergency PTCA, stents were implanted into the RCA and LAD. Patency was proven by angiography before the patient left the cardiac laboratory. Thirty minutes later the patient underwent CPR because of ventricular fibrillation. The patient died in cardiogenic shock. Postmortem examination showed a distinctly deformed LAD-stent. The case proves the possibility of a deformation of a coronary stent by resuscitation.

[Papillary muscle rupture during stress ECG after myocardial infarct]. / Papillarmuskelriss während eines Belastungs-EKGs nach Myokardinfarkt.

The case of a 57 year old patient is reported, who suffered from an acute myocardial infarction with maximum CK and CKMB values of 821 and 84 U/l, respectively. The patient underwent bicycle exercise testing 9 days after a myocardial infarction in 25 W steps every 2 min starting with 50 W. The ergometry was interrupted at 125 W because of ST segment depression of 0.28 mV in V6. Systolic blood pressure dropped to 55 mm Hg, combined with severe angina and shock. Volume substitution and catecholamines did not elevate blood pressure. Immediate M-mode and Doppler echo revealed a "stiletto"-shaped mitral regurgitation profile typical of acute mitral valve insufficiency. The transesophageal echocardiogram showed a distinct mass moving between the left ventricle and left atrium, diagnostic of papillary muscle rupture. Despite of shock, mitral valve replacement was performed successfully. To our knowledge, this is the first report of a papillary muscle rupture during exercise testing after myocardial infarction. Papillary muscle rupture can be induced by exercise. This fateful event may not be predicted by the course of the ergometry. In case of hypotension during exercise, papillary muscle rupture should be considered. The diagnosis is to be established by transesophageal echocardiography.

Interventional cardiology in Europe 1994. Working Group Coronary Circulation of the European Society of Cardiology.

The working group Coronary Circulation of the European Society of Cardiology conducts an annual survey of cardiac interventions in Europe with the support of the national societies of cardiology. A detailed questionnaire about cardiac interventions performed during 1994 was mailed to all members of the European Society of Cardiology. Incomplete or absent data from eight national members precluded their inclusion in the final analysis. Thus, this report summarizes the cardiac interventions performed during 1994 in 29 of 37 members of the European Society of Cardiology, representing a total population of approximately 490 million inhabitants. CORONARY ANGIOGRAPHY: A total of 922,687 coronary angiograms were reported during 1994, representing an increase of 22% compared with 1993 and of 35% compared with 1992. The mean incidence of coronary angiograms was 1881/10(6) inhabitants, ranging from 4417/10(6) inhabitants in Germany to 35/10(6) inhabitants in Romania, Germany, France, Great Britain, and Italy with 50% of the European population performed 73% of all cardiac interventions. CORONARY ANGIOPLASTY: During 1994, a total of 224,722 coronary angioplasty (PTCA) procedures were reported in Europe, an increase of 22% compared with 1993 and of 52% compared with 1992. Adjusted per capita, the mean incidence of coronary angioplasty was 458/10(6) inhabitants, ranging from 1091/10(6) inhabitants in Germany to 6/10(6) inhabitants in Romania. On average, the ratio PTCA per coronary angiogram was 0.24, ranging from 0.37 in the Netherlands to 0.06 in Cyprus. Ad hoc PTCA accounted for 22% of all PTCA cases. The majority (81%) of PTCAs were restricted to a single vessel. Major complications were reported in 2% of patients undergoing PTCA, including death (0.3%), myocardial infarction (1.0%) and need for emergency coronary artery bypass grafting (0.7%). CORONARY STENTING: Coronary stents were utilized in 21,599 coronary interventions during 1994, an increase of 235% compared with 1993 and thus representing the fastest growth in interventional cardiology. The number of European countries employing stents during coronary angioplasty grew from 14 during 1993 to 24 during 1994. Elective use (38%) became the most frequent indication for coronary stenting during 1994, replacing bail-out stenting as the primary indication during 1993. OTHER NEW DEVICES: Other new interventional therapeutic devices were employed in 8827 cases. Only the Rotablator was used more frequently during 1994 as compared with 1993. All other new therapeutic devices showed a decline. Coronary ultrasound was utilized in 3032 interventions and coronary angioscopy in 304 cases during 1994. NON-CORONARY INTERVENTIONS: Valvuloplasty remained the most frequent non-coronary intervention in Europe during 1994 with a total of 2622 mitral. 609 pulmonary and 506 aortic valvuloplasties. CATHETERIZATION FACILITIES: The number of facilities per 10(6) inhabitants performing invasive cardiac procedures in Europe during 1994 ranged from 7.7 in Iceland to 0.2 in Romania (European mean 2.9). The number of trained operators per 10(6) inhabitants ranged from 24 in Germany to 0.4 in Romania (European mean 10). During 1994, a mean of 701 coronary angiograms and 170 PTCAs were performed per catheterization facility in Europe (range: 1052 coronary angiograms and 293 PTCAs per facility in Norway to 218 coronary angiograms and 37 PTCAs per facility in Romania). CONCLUSIONS: The number of both coronary angiograms and coronary angioplasties continues to grow at an annual rate of approximately 20% in Europe. There is a wide range in the amount of revascularization procedures performed between western and eastern European countries. However, countries with the lowest numbers of coronary angiograms and coronary angioplasties, e.g. Romania, also show the fastest annual growth. About one quarter of all patients undergoing coronary angiography are subsequently revascularized by coronary angioplasty. (ABSTRACT TRUN

PTCA registry of German community hospitals. Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK) Study Group.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is widely used, but no quality control has been systematically performed as yet. METHODS: A registry of all PTCA procedures has been established since October 1992 for the majority of the German community hospitals performing PTCA, representing about one third of all PTCA activity in Germany. Baseline demographic data, indication for PTCA, primary success and in-hospital clinical events were recorded. Each centre was visited at regular intervals to assure completeness and reliability of the data. RESULTS: Of 52453 procedures performed from October 1992 to December 1994 the catheter laboratory and discharge forms were 99.7% and 98.1% complete, respectively. In 85.9% a single lesion was dilated per procedure, but 48.7% of the patients had multivessel disease. The success rate was 66.5% in complete occlusions (residual stenosis < 70%) and 91.2% in non-occluded vessels (residual stenosis < 50%). Abrupt vessel closure occurred in 3.4%, of which 77.5% could be recanalized by repeat intervention. In procedures not done for acute myocardial infarction, the in-hospital mortality was 0.52%, the procedure-related mortality 0.37%. In 3.02% of all patients a severe complication occurred (procedure-related death, myocardial infarction or emergency bypass surgery). CONCLUSION: Complete recording of all PTCA procedures is feasible even on a nationwide basis. This is a pre-requisite for continuous quality control. The reporting of the procedures by itself very probably, has an impact on the quality which is, however, not measurable quantitatively.

[Hemodynamic and humoral effects of parenteral therapy with intravenously administered ACE inhibitor quinaprilat in patients with advanced heart failure]. / Hämodynamische und humorale Auswirkungen einer parenteralen Therapie mit dem intravenös verabreichbaren ACE-Hemmer Quinaprilat bei Patienten mit fortgeschrittener Herzinsuffizienz.

The hemodynamic and neurohumoral effects of single and multiple doses of intravenous quinaprilat were assessed and compared with placebo in a double-blind design. The study group included 50 patients aged between 33 and 76 years with NYHA Class III and IV heart failure. The patients were randomized into three treatment groups to receive low (0.5 and 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) intravenous doses of quinaprilat or placebo on day 1, and, based on the responses, q6h on two further days. The hemodynamic parameters were determined by right-heart catheterization. Quinaprilat is the active metabolite of quinapril, an ACE inhibitor with high affinity for the angiotensin converting enzyme, which is formulated for oral application. Compared with placebo, single and multiple doses of quinaprilat increased cardiac index by 25% (p < 0.05) and simultaneously decreased both peripheral vascular resistance by 25% (p < 0.05) and left ventricular filling pressures by 33% (p < 0.05). There was a dose-related decrease in mean right atrial pressure by 47% (p < 0.05) without significant heart rate changes (-3-5 bpm). The mean artery pressure showed a dose-related maximum decrease of 4-9 mm Hg 45-60 min after single-dose quinaprilat and of 7-10 mm Hg (p < 0.05) after repetitive dosing. Maximum changes were observed 15-90 min after drug application. The hemodynamic changes after multiple-dose quinaprilat were similar to those observed following single doses and generally persisted during the total observation period of 6 h. Compared with placebo, quinaprilat reduced ACE activity and angiotensin II and aldosterone concentrations, and increased plasma renin activity. There were no significant changes with regard to plasma catecholamines and the atrial natriuretic factor, although a slight decrease could be observed. The study results obtained in patients with advanced heart failure support both the safety and favorable hemodynamic and neurohumoral effects of intravenous quinaprilat over an observation period of 3 days.

Interventional cardiology in Europe 1993. Working Group on Coronary Circulation of the European Society of Cardiology.

An annual survey on cardiac interventions in Europe is performed by the working group on Coronary Circulation of the European Society of Cardiology with the help of the national societies of cardiology. A questionnaire about cardiac interventions in 1993 was mailed to a representative of the national societies of 35 members of the European Society of Cardiology. The data collection of coronary interventions was delayed by slow backreporting and from 10 of the 35 national members data were missing or grossly incomplete. They were excluded from the analysis. CORONARY ANGIOGRAPHY: A total of 756,822 coronary angiograms were reported resulting in an incidence of 1146 +/- 1024 per 10(6) inhabitants, ranging from 24 (Romania) to 3499 (Germany). This represents an increase of 12% compared to 1992. Germany (279,882 cases), France (157,237), the United Kingdom (77,000), Italy (44,934) and Spain (37,591) registered 79% of all the coronary angiograms performed. PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY: A total of 183,728 percutaneous transluminal coronary angioplasty cases were reported in 1993, 24% more than in 1992. On average, they accounted for 18 +/- 7% (range 8 (Romania) to 35% (Sweden) of the coronary angiograms. Most of these percutaneous transluminal coronary angioplasties (82%) were confined to a single vessel. In 13% only, percutaneous transluminal coronary angioplasty took place immediately after the diagnostic study. Adjusted per capita. Germany ranks first with 873 percutaneous transluminal coronary angioplasties per 10(6) inhabitants, followed by France (737), Holland (725), Belgium (713), and Switzerland (665). The European mean of percutaneous transluminal coronary angioplasties per 10(6) inhabitants was 270 +/- 279, representing an increase of 14% compared with 1992. A major in-hospital complication was reported in 3.8% of the patients undergoing percutaneous transluminal coronary angioplasty: 0.6% hospital deaths, 1.5% emergency coronary artery bypass grafting, and 1.7% myocardial infarctions. NEW DEVICES: In 1993 stents were implanted in 6444 patients (3.5% of all percutaneous transluminal coronary angioplasty patients), equally distributed between bail-out situations (53%) and elective procedures. The 14 stent implanting countries showed a mean increase in incidence of coronary stenting of 53% compared with 1992. Other interventional devices were applied in 7045 cases, 3.8% of all percutaneous transluminal coronary angioplasty cases. Coronary ultrasound (2194 cases) and coronary angioscopy (380 cases) were performed infrequently. NON-CORONARY INTERVENTIONS: Valvuloplasties were most frequently performed non-coronary interventions European countries performed more than 300 valvuloplasties each in 1993. Most of them were mitral valvuloplasties in southern countries. CONCLUSIONS: Although partial backreporting might conclusions, several findings of this survey are noteworthy for the participating countries: The number of percutaneous taneous transluminal coronary angioplasties is universally increasing. There is an extremely wide range of coronary angiography and percutaneous translumina, coronary angioplasties performed per population. The most common additional procedure is a stent implantation while other new devices are only rarely applied. Mitral valvuloplasty is the most frequently performed non-coronary intervention.

Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart failure.

OBJECTIVE: To assess the pharmacodynamic activity and safety of rising single and multiple doses of intravenous quinaprilat compared with placebo in patients with New York Heart Association (NYHA) class III and IV congestive heart failure who were receiving digitalis or diuretic therapy or both. METHODS: Patients were randomly assigned to three treatment groups to receive low (0.5 to 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) single intravenous doses of quinaprilat or placebo on day 1. On the basis of responses observed on day 1, the three treatment groups received stable multiple intravenous doses of either quinaprilat or placebo every 6 hours on days 2 and 3. Hemodynamic measurements, hormonal assessments, and safety were evaluated before and at specified intervals during the study. RESULTS: Compared with placebo, single and multiple doses of quinaprilat increased cardiac index and reduced pulmonary capillary wedge pressure, mean arterial pressure, systemic vascular resistance, and right atrial pressure in a dose-related manner. No clinically important change in heart rate was observed. Hemodynamic changes after multiple-dose quinaprilat administration were similar to those observed after single doses and were generally sustained during the 6-hour dosing interval. Relative to placebo, quinaprilat reduced plasma angiotensin converting enzyme (ACE) activity, angiotensin II concentration, and aldosterone concentration and increased plasma renin activity; no prominent changes in plasma catecholamine and atrial natriuretic peptide concentrations were observed. There were no clinically important drug-related changes in the safety parameters. CONCLUSIONS: Single and multiple intravenous doses of 0.5 to 10 mg quinaprilat are well-tolerated and produce favorable dose-dependent hemodynamic effects and hormonal changes consistent with those expected of an ACE inhibitor in patients with NYHA class III and IV congestive heart failure.