[Clinical evaluation of pentaerythritol tetranitrate in two doses in patients with stable angina pectoris]. / Badania kliniczne czteroazotanu pentaerytrytylu w dwóch dawkach u pacjentów ze stabilna choroba wiencowa.

Pentaerythritol tetranitrate (PETN) has raised a great deal of interest in recent years, because it is probably the only organic "tolerance-sparing" nitrate. However, some clinicians doubt whether this drug is really effective in reducing angina and ischemia. The aim of this study, therefore, was to evaluate the clinical efficacy and adverse effects (AEs) of PETN in two doses: 50 mg (PETN-50) and 100 mg (PETN-100), after single ingestion. Twenty-five male patients (pts) with stable angina were enrolled in a randomized, double-blind and placebo (P) controlled study. Ten of them received PETN-50 or P and fifteen of them PETN-100 or P. Antianginal efficacy of the drugs was evaluated by analyzing the parameters of tolerance of effort and coronary reserve taken from serial exercise stress tests on the treadmill performed before single oral ingestion, then after 2h and 6h. Simple hemodynamic parameters were also evaluated at rest and during exercise. In comparison to P, PETN-50 did not change any parameter of tolerance of effort and coronary reserve, nor any simple hemodynamic parameter (all values statistically not significant - n.s.). However, in comparison to P, PETN-100 significantly improved the mean total walking time after 2h by 20.8% (p < 0.01) and also after 6h by 11.3% (p < 0.05). Similarly, PETN-100 improved walking time to angina after 2h by 18.8% (p < 0.05) and after 6h by 10.5% (p < 0.05). The drug also improved walking time to ischemia after 2h by 32.5% (p < 0.01) and after 6h by 13.8% (p < 0.05). PETN-100 did not significantly change the resting heart rate, but it decreased resting systolic blood pressure in both positions 6h after ingestion: in supine by 6.1% (p < 0.05) and in standing by 5.9% (p < 0.05). No postural hypotension in any pt occurred. Diastolic blood pressure significantly decreased only in standing position by 6.8% (p < 0.05) after 6h. During maximal exercise no significant reduction of systolic blood pressure occurred, but there was a significant reduction in diastolic blood pressure 6h after ingestion only. This study shows the good clinical tolerance and safety of PETN in both doses. There were no AEs after single ingestion of PETN-50 and AEs after ingestion of PETN-100 included headaches in 3 pts only (in 1 pt after P) in the group of 15 pts. Thus no clinical activity of PETN-50 was shown. However, our investigations suggest that PETN-100 is an active coronary drug, effective not less than 6 h after ingestion, and well tolerated by pts. Further studies are needed to evaluate the efficacy of PETN in long-term therapy.

[Clinical usefulness of high-dose oral nitroglycerin in patients with stable angina pectoris]. / Przydatnosc kliniczna nitrogliceryny w wysokiej dawce doustnej u chorych ze stabilna dlawica piersiowa.

The aim of this study was to evaluate clinical efficacy and adverse effects of nitroglycerin 15 mg in slow-release form (N-15) after single ingestion. In randomized, double-blind and placebo (P) controlled with cross-over design study 15 male patients with stable angina received N-15 or P. Antianginal efficacy of the drug was evaluated by analysing the parameters of tolerance of effort and coronary reserve taken from serial exercise stress tests on treadmill performed preceding single oral ingestion, 2 hours and 6 hours after. Simple hemodynamic parameters were also evaluated in the rest and during exercise. N-15 significantly improved in comparison to P: total walking time both after 2 hours by 34.3% (p < 0.01) and 6 hours by 23.1% (p < 0.01); walking time to angina after 2 hours by 34.8% (p < 0.01) and 6 hours by 21.7% (p < 0.05), and walking time to ischemia after 2 hours by 66.1% (p < 0.01) and 6 hours by 39.0% (p < 0.05). N-15 significantly increased the rest heart rate in standing position 2 hours after ingestion by 12.3% (p < 0.01) and decreased rest systolic blood pressure in both positions 2 hours after ingestion: in supine by 12.9% (p < 0.01) and standing by 16.3% (p < 0.01) and after 6 hours: in supine by 9.1% (p < 0.05) and standing by 10.0% (p < 0.05). No postural hypotension in any patient occurred. Diastolic blood pressure was significantly decreased only in standing position 2 hours after N-15 ingestion by 12.3% (p < 0.01) and after 6 hours by 9.1% (p < 0.05). During maximal exercise significant reduction of systolic blood pressure occurred 2 hours after ingestion and significant reduction of diastolic blood pressure occurred both 2 hours and 6 hours after ingestion. Adverse effects after single ingestion of N-15 were the few: the headaches were presented only in 4 patients (27%), and in 53% patients any adverse effect occurred. Nitroglycerin 15 mg in slow-release form is an active coronary drug, effective not less than 6 hours after ingestion, and its adverse effects are the few.