Nifedipine GITS versus diltiazem in chronic stable angina: a randomised multicentre study.

In order to compare the efficacy of nifedipine gastrointestinal therapeutic system (GITS) with diltiazem, 99 patients with chronic stable angina were studied in a parallel-group randomised trial. According to the results of the two exercise tolerance tests (ETTs) performed during the placebo run-in, patients were divided into a fixed threshold group if the variability in time to 1 mm ST-segment depression was 20%, or a variable threshold group if it was higher. Efficacy was assessed by comparing the time to 1 mm ST-depression on a bicycle ETT after 4 weeks of treatment, adjusting for the baseline value. The adjusted means were 7.44 min for nifedipine GITS and 7.68 min for diltiazem; the difference was -0.24 min, with a lower 90% confidence limit of -0.90, which is within the stated interval for equivalence. The same result was confirmed by the 'intention-to-treat' analysis, and comparable results were obtained both in fixed and in variable threshold groups. The incidence of side effects was 12% with nifedipine GITS and 8.2% with diltiazem. Nifedipine GITS and diltiazem were found to be equally effective in increasing exercise tolerance in chronic stable angina patients.

Reduced plasma nisoldipine concentrations in phenytoin-treated patients with epilepsy.

PURPOSE: To assess whether phenytoin affects the pharmacokinetics of the dihydropyridine calcium antagonist nisoldipine. METHODS: Twelve patients with epilepsy receiving chronic phenytoin therapy and 12 healthy control subjects matched for age and gender received a single oral dose of nisoldipine (40 and 20 mg, respectively). Blood samples were collected for up to 48 h for estimation of plasma nisoldipine levels by capillary gas chromatography. RESULTS: Mean plasma nisoldipine concentrations were much lower in the patients. Geometric means for areas under the concentration-time curve (AUC0-tn) normalized to a 20-mg dose were 1.6 micrograms/L/h (95% confidence intervals, 0.6-3.8 micrograms/L/h) in the patients compared with 15.2 (10.7-21.6) micrograms/L/h in control subjects (p < 0.002). CONCLUSIONS: These results suggest that phenytoin increases the first-pass metabolism of nisoldipine to a clinically important extent. In view of the magnitude and variability of interaction, use of nisoldipine in patients receiving chronic phenytoin therapy is contraindicated.

Susceptibility to pain during coronary angioplasty: usefulness of pulpal test.

OBJECTIVES: This study in patients with coronary artery disease (CAD) sought to 1) determine the dental pain threshold and reaction to tooth pulp stimulation; 2) correlate the clinical, ergometric and angiographic features of patients with and without pain during percutaneous transluminal coronary angioplasty (PTCA) to pulpal test response; 3) verify whether reactivity to dental pulp stimulation could help to identify patients particularly prone to perceiving angina during myocardial ischemia. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with CAD. Higher pain thresholds have been documented in asymptomatic subjects, suggesting a generalized hyposensitivity to pain. METHODS: Eighty-six consecutive male patients with reproducible exercise-induced myocardial ischemia and CAD documented by angiography underwent PTCA. A pulpal test was performed in all patients by means of an electrical tooth pulp stimulator. RESULTS: Seventy-one patients (82.6%) with and 15 (17.4%) without angina during daily life were studied. During the pulpal test, 57 patient (66.2%) reported dental pain, whereas 29 (33.7%) were asymptomatic, even at maximal stimulation of 500 mA. The study cohort was classified into two groups according to the presence (58 patients [group 1]) or absence (28 patients [group 2]) of angina during myocardial ischemia induced by PTCA. Ergometric variables, extent of CAD, presence of ST segment elevation during PTCA, number of inflations, inflation time and maximal inflation pressure were similar in the two patient groups. Dental pain was provoked by pulpal test in 81% of patients with and 36% of patients without symptoms during PTCA (p = 0.0004). The absence of dental pain even at maximal tooth pulp stimulation (500 mA) was observed in 11 (18.9%) patients in group 1 and 18 (64.2%) in group 2. Patients who were asymptomatic during PTCA had a higher mean dental pain threshold, lower mean threshold reaction and lower mean maximal reaction than those who were symptomatic during both PTCA and the pulpal test. CONCLUSIONS: A correlation between the prevalence of symptoms during pulpal test, daily life, exercise-induced myocardial ischemia and PTCA was found. A higher dental pain threshold and lower reactivity characterized those subjects who were prone to silent ischemia both during daily life and during PTCA. Ergometric variables, extent of CAD and techniques used during PTCA were unrelated to the tendency to perceive pain during myocardial ischemia. Response to the pulpal test and the presence of symptoms during daily life were highly related to the presence of angina during PTCA.

Beta-endorphins during coronary angioplasty in patients with silent or symptomatic myocardial ischemia.

OBJECTIVES: The aims of this study were to correlate beta-endorphin plasma levels and anginal pain in patients with ischemia induced by percutaneous transluminal coronary angioplasty and to detect eventual endorphin variations during balloon occlusion. BACKGROUND: The opioid system appears involved in the absence of pain occurring in silent myocardial ischemia. METHODS: Beta-endorphin plasma levels were measured 24 h before, just before, during and after coronary angioplasty (performed on the left anterior descending artery) in 53 men with documented coronary artery disease and exercise-induced myocardial ischemia. RESULTS: Group 1 (33 patients) reported symptoms; group 2 (20 patients) was asymptomatic during angioplasty. In these patients, the prevalence of exercise-induced silent ischemia was 57%. The occurrence of angina during exercise or angioplasty was related to the frequency of angina during daily life when patients were subgrouped. The severity and distribution of coronary artery disease did not differ between the two groups. During angioplasty, the number of balloon inflations and the inflation time and pressure were similar in symptomatic and asymptomatic patients. In each group, no short-term variability of baseline beta-endorphin plasma levels was observed during 2 consecutive days. Corresponding beta-endorphin plasma levels (at baseline and during and after angioplasty) were significantly higher in Group 2. During balloon occlusion, the levels decreased significantly in the symptomatic group at the onset of angina but remained stable in the asymptomatic group. CONCLUSIONS: Methodologic variables and the severity of coronary artery disease did not influence the presence of symptoms during angioplasty-induced ischemia. Beta-endorphin plasma levels were higher and more stable in patients with silent ischemia during angioplasty, suggesting that opiate levels and their variation during ischemia are associated with individual attitude toward anginal pain.

Significance of hyperventilation-induced ST segment depression in patients with coronary artery disease.

To investigate the significance of hyperventilation-induced ST segment depression, 329 consecutive patients with angina and documented coronary artery disease who underwent hyperventilation and exercise tests during pharmacologic washout were studied. The hyperventilation test induced ST segment depression in 79 patients. In 36 of these 79 patients, the electrocardiographic changes occurred early during overbreathing (Group I), whereas in 26 they occurred late during recovery (Group II). Seventeen patients developed ST segment depression both during over-breathing and during recovery (Group III). Group I patients had a higher frequency of history of angina during exercise, multivessel disease and lower tolerance to exercise as compared with patients in Group II. In Group I, the rate-pressure product at the time to onset of ST depression during overbreathing was similar to that during exercise (152 +/- 24 versus 148 +/- 42; p = NS), whereas in Group II the rate-pressure product at the time to onset of ST depression during recovery was comparable with that under control conditions (104 +/- 30 versus 98 +/- 27; p = NS) and far less than that required to produce ischemia during exercise (104 +/- 30 versus 201 +/- 56; p less than 0.0011). In nine Group III patients, the acute administration of propranolol prevented the early hyperventilation-induced ST segment depression, whereas nifedipine abolished the delayed hyperventilation-induced ST segment depression. These findings suggest that early hyperventilation-induced ST segment depression is due to increased oxygen demand in patients with poor coronary reserve and may be prevented by beta-adrenergic blockers, which are useful for lowering oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)