Propionyl-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina.

The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L-carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L-carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway.

Evaluation of pentisomide on stable ventricular premature beats. Comparison with placebo.

Pentisomide, a new class I anti-arrhythmic drug, was compared to placebo in 50 hospitalized patients with frequent (greater than 30 h-1) and stable ventricular premature beats (VPB) (variation less than 50% between two preliminary and one placebo 24-h Holter recordings). All patients underwent a single-dose acute oral testing followed by a short-term testing with 300 mg t.i.d. for 4 days and then by a 4-day placebo period. For the studied population, a 56.4% reduction of simple VPB and a 98.8% decrease of couplets and runs were the minimum required to define the drug efficacy and to exclude spontaneous variability, using the linear regression analysis. Pentisomide was found effective in 27 (54%) of the 50 patients after the acute test and in 23 (46%) after the short-term test. The drug induced a mild increase of PR and QRS intervals, while QTc, heart rate, blood pressure and ejection fraction showed no significant variations. Subjective tolerability was excellent.

[Efficacy and length of action of a slow-release formulation of isosorbide-5-mononitrate in stable effort angina]. / Efficacia e durata d'azione di una formulazione a lento rilascio di isosorbide-5-mononitrato nell'angina da sforzo stabile.

This double-blind randomized placebo-controlled study was designed to evaluate the acute effects of orally administered slow-release isosorbide-5-mononitrate (SR IS-5-MN) in 12 patients with chronic stable angina. After a prestudy screening to assess the reproducibility of exercise response, the patients entered the study lasting 5 days. On the first and fourth day of the trial, each patient underwent a bicycle exercise test 4, 8 and 24 hours after acute administration of SR IS-5-MN 50 mg or placebo. Statistic analysis of the results was performed using a 2-way analysis of variance for cross-over design. Compared to placebo, 4 hours after administration, SR IS-5-MN prolonged the exercise time from 525 +/- 162 s to 685 +/- 207 s (p less than 0.05; 30%) and - 1mm time from 437 +/- 147 s to 562 +/- 219 (p less than 0.05; 29%). After 8 hours SR IS-5-MN prolonged the exercise time from 510 +/- 145 s to 615 +/- 189 s (p:ns; 21%), and - 1mm time from 415 +/- 128 s to 522 +/- 205 s (p less than 0.05; 26%). No significant changes were observed 24 hours after SR IS-5-MN administration. The maximal rate-pressure product was significantly increased by SR IS-5-MN 4 hours after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective evaluation of gallopamil in patients with chronic stable angina. Exercise testing, Holter monitoring, cross-sectional echocardiography and plasma levels.

In this double-blind, randomized placebo-controlled study the effects of two dosages of gallopamil on exercise tolerance were evaluated in 12 patients with stable effort angina. After a pre-study screening aimed at assessing the reproducibility of the exercise response, the patients entered the study which consisted of three 7-day consecutive periods during which placebo or gallopamil 50 mg t.i.d. or gallopamil 75 mg t.i.d. were administered according to a randomized sequence. 24-hour Holter monitoring and cross-sectional echocardiography were performed on the 6th and 7th day of each treatment period, respectively. On the 7th day of each treatment period, patients underwent an exercise test 2 and 8 h after the last administration of gallopamil or placebo. Blood samples for plasma gallopamil concentrations were taken just before each exercise test. The results were analysed using a three-way analysis of variance; intergroup differences were evaluated by the Newman-Keuls test. At 2 h, 11 patients with placebo and three with gallopamil experienced angina; both dosages of gallopamil significantly prolonged exercise time and -1 mm time and also reduced ST segment depression and the rate-pressure product at submaximal workload. No significant change in the rate-pressure product was observed either on the appearance of 1 mm ST depression or at peak exercise. At 8 h, 11 patients with placebo and gallopamil 50 mg t.i.d. and 10 with gallopamil 75 mg t.i.d. experienced angina; although exercise time was significantly prolonged by both dosages of gallopamil, the increase in -1 mm time and reduction of ST segment depression at submaximal workload did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized placebo-controlled comparative study of nifedipine, verapamil and isosorbide dinitrate in the treatment of angina at rest.

Twenty-nine patients with angina at rest took part in a randomized placebo-controlled short-term study to assess the relative effectiveness of different dosages of nifedipine (N), verapamil (V) and isosorbide dinitrate (ISDN) versus placebo and to evaluate the antianginal effects of a sustained-release preparation of ISDN (sr), of N retard form (r) and of V retard form (r). The 29 patients were divided into 3 groups: the first group of patients (10 patients, group A) was treated with N 10 mg six times daily, V 80 mg three times daily and ISDN 10 mg six times daily; the second group of patients (9 patients, group B) was treated with N 20 mg six times daily, V 120 mg four times daily and ISDN 20 mg six times daily; the third group of patients (10 patients, group C) was treated with N r 20 mg four times daily, V r 120 mg three times daily and ISDN sr 40 mg four times daily. The daily frequency of ischaemic episodes (IE) was assessed by Holter monitoring. The effect of each drug on the mean frequency of IE was compared with the placebo using a one-way analysis of variance and the Newman-Keuls test. In group A, the mean daily frequency of IE per patient was 8.1 +/- 5.9 with the placebo, 1.4 +/- 1.9 with N (P less than 0.001; -82%), 4 +/- 3.6 with V (P: NS; -50%) and 4.3 +/- 3.6 with ISDN (P: NS; -46%). In group B it was 6.4 +/- 3.4 with the placebo, 0.5 +/- 1.6 with N (P less than 0.01; -91%), 0.3 +/- 0.5 with V (P less than 0.01; -95%) and 1.2 +/- 1 with ISDN (P less than 0.01; -82%). In group C it was 10.3 +/- 8.7 with the placebo, 0.7 +/- 1.6 with N r (P less than 0.01; -93%), 1 +/- 2.5 with V r (P less than 0.01; -90%) and 5.1 +/- 7.7 with ISDN sr (P: NS; -50%). In group A a reduction of 100% in the number of recorded IEs was achieved in 5/10 patients by using N, in none by V, and in 1/10 by ISDN. In group B, in 8/9 patients by N, in 6/9 by V and in 3/9 by ISDN. In group C, in 8/10 patients by both N r and V r in 4/10 patients by ISDN sr.(ABSTRACT TRUNCATED AT 400 WORDS)

[Efficacy and duration of action of isosorbide-5-mononitrate in the treatment of stable angina of effort. Comparison with sustained-release isosorbide dinitrate]. / Efficacia e durata d'azione dell'isosorbide-5-mononitrato nel trattamento dell'angina da sforzo stabile. Confronto con l'isosorbide dinitrato a cessione ritardata.

A new compound, Isosorbide-5-mononitrate (IS-5-MN; 40 mg orally), was compared with sustained-release Isosorbide dinitrate (SRDI; 40 mg orally) in 18 patients with chronic exercise-induced angina pectoris. The patients were studied in a randomized placebo-controlled single-blind trial. Multistage bicycle test with computer-assisted electrocardiographic analysis was performed before, 60-90, 240 and 360 minutes after treatment administration. Both drugs significantly and comparably prolonged exercise time (p less than 0.01) and time to development of 1 mm ST-segment depression (p less than 0.01) at the 3 times of study. At the highest common level of work, ST-segment depression and its integral were significantly reduced by both IS-5-MN and SRDI compared to placebo (p less than 0.01); conversely, the peak ST-segment depression was unaffected. Compared to placebo, a significant increment in maximal heart rate/systolic blood pressure was observed after drug administration. It is concluded that 40 mg of orally administered IS-5-MN is effective during at least 6 hours and that its therapeutic action is comparable to that of SRDI.

Ischaemia related ventricular arrhythmias in patients with variant angina pectoris.

UNLABELLED: Twenty-three patients with variant angina were studied by Holter monitoring both to assess the incidence of serious ventricular arrhythmias (a risk factor of sudden death in variant angina), during ischaemic episodes and to examine the time-relation of the arrhythmias to ST changes. Serious ventricular arrhythmias were observed in 12/23 patients (52%). In the 23 patients, a total of 491 episodes of ST segment elevation were recorded during 954 h of Holter monitoring; serious ventricular arrhythmias were found in only 46 ischaemic episodes (9.4%). Six out of 12 patients showed serious ventricular arrhythmias at the onset of ischaemic episodes or during maximal ST elevation (phase 1), one patient during return or immediately after return of ST to baseline (phase 2) and five patients during both phases. Thirty-three out of 46 ischaemic episodes (76%) showed serious ventricular arrhythmias during phase 1, eight (17%) during phase 2, and five (11%) during both phases. Serious ventricular arrhythmias were neither related to previous myocardial infarction nor to the presence of serious ventricular arrhythmias during inter-crisis periods, whereas a good relationship with severity of ischaemic episodes, as assessed by the magnitude and duration of ST elevation, was found. A modest relationship with anterior ST elevation was also found. IN CONCLUSION: (1) serious ventricular arrhythmias occur in a high percentage of variant angina patients, but in only a small proportion of ischaemic episodes; (2) serious ventricular arrhythmias are related to the severity of ischaemia and occur predominantly at the onset of ischaemic episodes and/or during maximal ST elevation; in only a few cases do they occur during resolution of ischaemic episodes.

[Comparison of the efficacy of propafenone and hydroquinidine in stabilized extrasystolic ventricular arrhythmia by means of dynamic electrocardiographic Holter monitoring]. / Confronto dell'efficacia del propafenone e dell'idrochinidina nella aritmia extrasistolica ventricolare stabilizzata mediante monitoraggio elettrocardiografico dinamico secondo Holter.

The aim of our study has been to evaluate the efficacy of Propafenon by a reliable experimental method. We have compared the efficacy of Propafenon (300 mg three times daily) with that of Dihydroquinidine Chloride at an elevated dose (300 mg six times daily). Twelve patients, with chronic arrhythmia (at least 1500 premature ventricular beats - PVBs - during a preliminary 24-hour dynamic electrocardiographic Holter monitoring), have been studied. The study has been performed in a double-blind cross-over fashion, and the drugs were administered according to a randomized sequence by the double dummy technique for 4 days. Placebo administration periods of similar duration were established before, after and between the two periods of drug administration. At the end of each Propafenon Dihydroquinidine Chloride and Placebo administration period a 48-hour Holter monitoring was performed. The number of PVBs/hour measured during the 3 periods of Placebo administration (714 +/- 418, 804 +/- 422, 779 +/- 433 respectively) confirmed the chronic nature of the ventricular arrhythmia and the absence of spontaneous variations during the study. Treatment with Propafenon and Dihydroquinidine Chloride significantly reduced the number of PVBs/hour to 87 +/- 130 and to 216 +/- 453 respectively. The reduction observed during Propafenon administration was more than observed during Dihydroquinidine Chloride administration, but it was not statistically significant because of the different behaviour of the individual patients. All patients but one had an over 65% reduction of PVBs/h; only 8/12 patients showed a reduction greater than 65% during Dihydroquinidine Chloride administration.(ABSTRACT TRUNCATED AT 250 WORDS)