Double-blind randomized multicenter study on the efficacy of trapidil versus isosorbide dinitrate in stable angina pectoris.

BACKGROUND: Trapidil is an inhibitor of phosphodiesterase I-IV with resulting positive lusitropic, vasodilating, and antiplatelet effects. HYPOTHESIS: This study was undertaken to compare the antianginal efficacy of trapidil with that of isosorbide dinitrate (ISDN) in patients with stable angina pectoris. METHODS: We studied 95 patients with stable angina pectoris who were randomized into a double-blind parallel group study with either oral trapidil or ISDN. After a 1-week run-in period and a 2-week wash-out phase, the patients received either trapidil 200 mg t.i.d. (n = 48) or ISDN 20 mg t.i.d. (n = 47) for 12 weeks. All antianginal medication, except sublingual glyceryl trinitrate (GTN), was discontinued during the study. Patients underwent an exercise electrocardiogram on an ergometer bicycle according to a modified Bruce protocol before and at 6 and 12 weeks during treatment. RESULTS: The workload capacity increased from 583 +/- 281 W.min before treatment to 833 +/- 444 W.min after 12 weeks of treatment in the trapidil group (p < 0.01) and from 555 +/- 276 W.min to 827 +/- 361 W.min in the ISDN group (p < 0.01). The anginal attacks per week as well as the use of GTN decreased significantly in both groups. After 12 weeks of therapy, the cumulative ST-segment depression during exercise decreased by 67% in the trapidil patients and by 23% in the ISDN patients. Compared with baseline, the double product at the 75 W level was reduced in both groups after 12 weeks of treatment. Blood pressure and heart rate at rest remained nearly unchanged. Overall, no statistical difference was found between the two study groups. The tolerability was good. CONCLUSION: Oral trapidil therapy is safe and effective in stable angina pectoris and is equivalent to standard therapy with ISDN.

[Renal artery dilatation in renovascular hypertension. Acute and long-term outcome in a large patient sample]. / Nierenarteriendilatation bei renovaskulärer Hypertonie. Akut- und Langzeitergebnisse eines grossen Patientenkollektivs.

BACKGROUND: Renal angioplasty is an established therapy for treatment of renovascular hypertension. This study was performed to evaluate short- and long-term outcome of this procedure up until 3 years afterwards. PATIENTS AND METHODS: Altogether, 111 renal artery stenosis in 92 patients were dilated. Among these were 31 fibromuscular and 70 arteriosclerotic lesions, 4 transplant artery stenosis and 6 occlusions. RESULTS: The primary success rate for dilatation was approximately 90%. Serious complications occurred in 5 of the patients including 2 fatal myocardial infarctions about 2 weeks after the procedure. Restenosis (altogether 25%) almost exclusively occurred during the first few months after angioplasty (more often in arteriosclerotic lesions than in fibromuscular disease). Successful dilatation resulted in better blood pressure control. In several patients with preexisting chronic renal failure improvement of renal function was observed; in this group, however, restenosis occurred in about 1 third of the patients. CONCLUSIONS: Renal angioplasty is a suitable method for therapy of renovascular hypertension; in patients with preexisting renal failure improvement of renal function may ensue. The decision to treat with angioplasty must be weighted carefully against other established and also newer methods (surgery vs. antihypertensive medication vs. stent implantation) and should be reserved for specialized centers.

[Balloon mitral valve commissurotomy in pregnancy]. / Ballon-Mitralkommissurotomie in der Schwangerschaft.

HISTORY AND CLINICAL FINDINGS: A 31-year-old woman with known postrheumatic mitral valve stenosis developed for the first time left heart failure in the 19th week of her fifth pregnancy. After intensive drug treatment she was in stage 3 (New York Heart Association classification). Apart from that the patient was in a good general condition and obstetrical status was according to the estimated duration of pregnancy. Auscultation revealed an apical diastolic murmur and mitral opening snap. INVESTIGATIONS: Echocardiography demonstrated a mitral valve opening area of 0.85 cm2 (pressure-half time method); the mean gradient was 19 mm Hg. TREATMENT AND COURSE: Because of the severity of the findings a percutaneous transvenous balloon valvotomy (according to Inoue) was performed in the 27th week of pregnancy, after careful lead shielding of abdomen and pelvis. Radiological screening time was 10 min. The invasively measured transvalvar pressure gradient was reduced from 28 to 4 mm Hg, echocardiographically determined mitral opening area increased to 1.5 cm2. Delivery was induced in the 36th week of pregnancy because of third-degree renal pelvis congestion. A healthy child, weighing 2850 g was delivered vaginally. CONCLUSION: High-grade symptomatic mitral stenosis can, if necessary, be treated with a low-risk to mother and child by percutaneous balloon valvotomy.

Long-term effects of balloon coarctation angioplasty on arterial blood pressure in adolescent and adult patients.

In patients with coarctation of the aorta arterial hypertension frequently persists when surgical repair is performed after age 20 years. There are little data on the long-term effect of angioplasty and the question remains to be determined whether hypertension is sufficiently treated by this procedure. Twenty-nine consecutive patients (9 females and 20 males) 14 to 54 years old (median, 25) underwent angioplasty for native coarctation of the aorta. Twenty-five patients (86%) had pre-existing systolic arterial hypertension (> 140 mm Hg). The mean peak systolic pressure gradient decreased from 62 +/- 18 to 21 +/- 13 mm Hg immediately after angioplasty. At hospital discharge 13 patients still had hypertension. After a mean follow-up interval of 4.0 years (range, 0.3-9.5) the residual peak pressure gradient was 14 +/- 13 mm Hg. Blood pressure was normal without antihypertensive therapy in 23 patients (79%). In the six hypertensive patients the pressure gradients were 7, 13, 30, 30, 35, and 60 mm Hg. One patient died 8 months after angioplasty and another underwent surgery for aortic aneurysm. Although this was an uncontrolled study the data suggest that normalization of blood pressure may occur more frequently after angioplasty than after surgery in adolescents and adults with native coarctation.

[Acute hemodynamic effects of piroximone i.v. in patients with severe heart failure]. / Akute hämodynamische Effekte von Piroximon i.v. bei Patienten mit schwerer Herzinsuffizienz.

UNLABELLED: Forty patients (30 men, 10 women) with severe congestive heart failure NYHA III (n = 30) and IV (n = 10) due to coronary heart disease (n = 19) or dilative cardiomyopathy (n = 21) were enrolled in this study. Mean age was 57 years. Eight patients each received 0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg piroximone intravenously or placebo (saline). Measurements were performed before and up to 4 h after drug administration using a Swan-Ganz right-heart thermodilution catheter. RESULTS: All changes stated were significant (p < 0.05). Pulmonary capillary wedge pressure was lowered by max. 27% (0.25 mg/kg) to 52% (2.0 mg/kg) 30 min after drug injection. Significant effects were seen for 60 (0.25 mg/kg) to 120 min (2.0 mg/kg). Mean pulmonary artery pressure decreased by max. 8% to 24% after 30 min. Effects lasted for 30 to 60 min. Cardiac index increased by max. 26% to 52% after 30 min. Significant changes occurred up to 4 h after 2.0 mg/kg. Systemic vascular resistance fell by max. 16% to 34%. Effect duration was 1 h (0.5 mg/kg up to 4 h) (2.0 mg/kg). Minor changes of arterial blood pressure (minus 7% after 0.5 mg/kg) and heart rate (minus 14% after 2.0 mg/kg) were seen. CONCLUSION: Small doses of piroximone i.v. increase cardiac output by about 20% while preload and afterload decrease by about 20%. For most cases no doses higher than 0.5 mg/kg will be needed for the treatment of severe congestive heart failure.

Captopril in acute myocardial infarction: beneficial effects on infarct size and arrhythmias.

It is known from experiments that angiotensin-converting enzyme inhibitors can limit infarct size. In a prospective, randomized, placebo-controlled double-blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 and 18 h from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With the exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV, p < 0.05). The number of ventricular premature beats at 24 h from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred seven times in the placebo group, but did not occur in the captopril group. The creatine kinase infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). Mean arterial pressure was reduced by 12 mmHg with captopril treatment. The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.

Captopril in acute myocardial infarction. Beneficial effects on infarct size and arrhythmias.

OBJECTIVE: It is known from experiments that angiotensin converting enzyme (ACE) inhibitors can limit infarct size. We examined the effect in patients. METHODS: In a prospective, randomized, placebo-controlled double blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 hours and 18 hours from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. RESULTS: The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV) (p < 0.05). The number of ventricular premature beats at 24 hours from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred 7 times in the placebo group, but did not occur in the captopril group. The creatine kinase (CK) infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). The mean arterial pressure was reduced by 12 mmHg with captopril treatment. CONCLUSIONS: The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.

[The effect of intracoronary infused captopril on luminal width in coronary stenosis]. / Einfluss von intrakoronar infundiertem Captopril auf die Lichtungsweite bei Koronarstenosen.

To elucidate the mechanism of anti-ischaemic and anti-anginal action of angiotensin-converting-enzyme inhibitors, a randomized double-blind study was undertaken in 30 consecutive patients (27 men, 3 women; mean age 58 [28-70] years) with stable angina and at least 50%, angiographically well demonstrated, stenosis of one of the main coronary artery branches. They received an intracoronary infusion of either 0.5 mg captopril (n = 16) or of a placebo (n = 14) to see whether in this form of application the drug could cause an acute dilatation of a coronary stenosis. The diameter before captopril administration was 1.40 +/- 0.63 mm, while 1, 5 and 10 min after infusion it was 1.49 +/- 0.58 mm, 1.30 +/- 0.54 mm and 1.41 +/- 0.59 mm (not significant). There was also no significant difference between captopril and the placebo. The absence of effect with captopril may be due to insufficient liberation of endothelium-derived relaxing factor in an arteriosclerotic coronary segment.

[Follow-up angiography after balloon dilatation of aortic isthmus stenoses in adults]. / Angiographische Verlaufskontrollen nach Ballondilatation von Aortenisthmusstenosen bei Erwachsenen.

Between May 1985 and April 1991, 30 patients (seven females and 23 males) 14 to 54 years old (median, 25 years) underwent balloon angioplasty for unoperated native (n = 26) or recurrent postoperative (n = 4) coarctation of the aorta. 28/30 patients had systemic hypertension (RR > 140/90 mmHg). Dilatation of the stenotic segment could be achieved in 28/30 patients. The residual pressure gradient was > 30 mmHg in six patients. In 2/4 patients with recurrent coarctation the balloon had ruptured, while dilatation was successful in the other two patients. The mean diameter of the stenotic segment increased from 5.8 +/- 2.7 mm to 11.9 +/- 2.5 mm and the peak pressure gradient decreased from 61 +/- 18 mmHg to 20 +/- 13 mmHg. Complications were a small hemorrhagic pleural effusion in one patient and a groin hematoma in another patient. Clinical follow-up studies with retrograde catheterization of the aorta and angiography were performed in all 28 patients with dilated coarctation, 6 months to 6 years after the procedure, representing a total follow-up time of 72 (average, 2.6) patient-years. Multiple follow-up studies (n = 2-4) were performed in 17/28 patients. In one patient the first angiogram revealed aneurysm formation while a small bulge was seen in two others. Intra-aortic pressure measurements revealed a peak gradient of < 30 mmHg in 24/28 patients with a mean of 14 +/- 10 mmHg. The blood pressure was normal in 23/28 patients. In the other five patients whose pressure gradients were 7, 30, 30, 35, and 60 mmHg moderate hypertension persisted.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of captopril in nitrate tolerance]. / Wirkung von Captopril bei Nitrattoleranz.

To test whether angiotensin-converting-enzyme (ACE) inhibitor can counteract nitrate tolerance, 15 men (mean age 65 [55-69] years) were studied. They all had an at least 75% stenosis of a main coronary artery branch, proven by coronary angiography no longer than 6 months previously. Each patient underwent six ergometric tests (two each per day on alternate days) at constant exercise level and duration: the sum of S-T segment depressions was measured during the recovery and exercise minutes. The initial ergometry test was done without medication, when the S-T segment sum was 1.15 +/- 0.20 mV. After 25 mg captopril (2nd ergometry period) this sum fell to 0.80 +/- 0.18 mV. Two hours after application of a nitrate plaster the S-T segment sum was 0.55 +/- 0.12 mV (3rd ergometry period). Adding 25 mg captopril a further reduction to 0.35 +/- 0.10 was achieved (4th ergometry period). Subsequently, continuous nitrate application brought about nitrate tolerance. The 5th ergometry period then produced a sum of S-T segment depressions of 0.85 +/- 0.18 mV. Renewed captopril administration reduced this value to 0.50 +/- 0.13 mV (57% of the initial value). The effect of captopril in nitrate tolerance is apparently due to an addition of the anti-ischaemic action of the ACE inhibitor (31%) and the residual effect of the nitrate (26%).

[Nitroglycerin in comparison with nifedipine in patients with hypertensive crisis]. / Nitroglycerin im Vergleich zu Nifedipin bei Patienten mit hypertensiver Krise.

To determine whether nitroglycerin is just as effective as nifedipine in lowering the blood pressure in excessive hypertension and hypertensive crisis, two groups of 20 patients received in random sequence either 1.2 mg of nitroglycerin sublingually or a 10 mg nifedipine capsule, which was chewed and swallowed. The blood pressure fell after 5 min in the nitroglycerin group from 211/122 mm Hg to 171/95 mm Hg and after nifedipine from 210/118 to 185/102 mm Hg. The greater effect of nitroglycerin results from faster absorption through the oral mucosa than through the small intestinal mucosa where nifedipine is primarily absorbed. After 15 to 20 min a satisfactory reduction in blood pressure was reached in both groups: 157/91 and 158/92 mm Hg, respectively. After 30 min the heart rate in the nitroglycerin group had decreased from 83 to 80/min, but in the nifedipine group it had increased from 84 to 90/min. The reduction in blood pressure persisted up to 6 h. No significant difference in side-effects was determined. Since a hypertensive crisis is usually accompanied by left-ventricular failure, pulmonary edema or angina pectoris and infarction, and nitroglycerin has been definitively shown to positively influence these conditions, preference should be given to nitroglycerin in the treatment of hypertensive crisis.

Comparison of nitroglycerin with nifedipine in patients with hypertensive crisis or severe hypertension.

To determine whether nitroglycerin is as effective as nifedipine in lowering the blood pressure in severe hypertension and hypertensive crisis, two groups of 20 patients received in random sequence either 1.2 mg nitroglycerin sublingually or a 10-mg nifedipine capsule, which was chewed and swallowed. The blood pressure fell after 5 min in the nitroglycerin group from 211/122 mmHg to 171/95 mmHg and after nifedipine from 210/118 to 185/102 mmHg. The greater effect of nitroglycerin may result from faster absorption through the oral mucosa than through the small intestinal mucosa where nifedipine is primarily absorbed. After 15-20 min a satisfactory reduction in blood pressure was reached in both groups: 157/91 and 158/92 mmHg, respectively. After 30 min the heart rate in the nitroglycerin group had decreased from 83 to 80/min, but in the nifedipine group it had increased from 84 to 90/min. The reduction in blood pressure persisted up to 6 h. No significant differences in side effects were determined. Since a hypertensive crisis is usually accompanied by left ventricular failure, pulmonary edema, angina pectoris, or infarction, nitroglycerin has been definitively shown positively to influence these conditions, and preference should be given to nitroglycerin in the treatment of hypertensive crises.