Donna M. Christensen

Comparison of nifedipine and propranolol used in combination with diuretics for the treatment of hypertension.

One hundred patients participated in a double-blind, randomized study to compare the antihypertensive efficacy of sustained-release nifedipine and propranolol in hypertensive patients whose diastolic blood pressure exceeded 95 mm Hg while receiving diuretic therapy. Nifedipine (mean dose, 79.6 mg per day) decreased blood pressure by 11.4/10.5 mm Hg; propranolol (mean dose, 198.4 mg per day) decreased blood pressure by 13.5/10.3 mm Hg. Reduction of diastolic blood pressure to below 90 mm Hg was achieved in 63 percent of nifedipine-treated patients and in 57 percent of propranolol-treated patients. Nifedipine therapy was associated with an increase in high-density lipoprotein cholesterol levels and a decrease in serum triglyceride levels. In contrast, propranolol therapy was associated with a decrease in high-density lipoprotein cholesterol levels and an increase in serum triglyceride levels. Nifedipine is as effective as propranolol in the treatment of patients with mild to moderate hypertension whose blood pressure is inadequately controlled by diuretic therapy.

Left ventricular ejection fraction response during exercise in asymptomatic systemic hypertension

To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine, but not propranolol, improves left ventricular systolic and diastolic function in patients with hypertension

The effects of nifedipine and propranolol on cardiac function both at rest and at peak exercise were compared in 22 hypertensive patients whose diastolic blood pressures remained in excess of 95 mm Hg despite diuretic therapy. In this double-blind, placebo-controlled study, left ventricular systolic and diastolic function at rest and at peak exercise during bicycle ergometry was assessed by first-pass radionuclide angiography using the Baird Scinticor before and after treatment with either nifedipine or propranolol. Both agents effectively reduced blood pressure in the supine and upright positions and at peak exercise. Nifedipine was associated with a significant increase in cardiac output and stroke volume at rest and at peak exercise, while propranolol decreased cardiac output at rest and at peak exercise. Systemic vascular resistance decreased with nifedipine treatment at rest and at peak exercise, but increased significantly with propranolol. Nifedipine increased ejection fraction in patients at rest and also increased maximal oxygen consumption at peak exercise, while propranolol decreased maximal oxygen consumption at peak exercise. At rest and at peak exercise, nifedipine increased peak filling rate, but time to peak filling rate was not affected by either drug. The fraction of total diastolic filling at the midpoint of diastole was significantly increased by nifedipine therapy at rest but was not affected by propranolol therapy. Nifedipine significantly decreased atrial filling volume while propranolol had no effect. Propranolol therapy did not result in any improvement in left ventricular function. In contrast, nifedipine improved left ventricular systolic and diastolic function at rest and peak exercise. Future selection of an antihypertensive agent should include consideration of the impact of therapy on left ventricular function.

Effect of bepridil in patients with chronic stable angina: results of a multicenter trial.

The effects of bepridil, a calcium antagonist with a half-life of approximately 42 hr, were assessed in a double-blind, randomized, placebo-controlled crossover trial. Forty-four patients (39 men, five women) with exercise-induced angina pectoris and ST segment depression with exercise testing (modified Bruce protocol) were studied. Compared with placebo bepridil (400 mg daily) increased total exercise time, time to onset of angina, time to 1 mm of ST segment depression, time to 2 mm of ST segment depression, and total work achieved (all p less than or equal to .001). Both frequency of angina and nitroglycerin consumption decreased during the bepridil compared with the placebo period (p = .02 and .03, respectively). Minor side effects were noted during both the bepridil and placebo phases. Four patients experienced side effects that limited therapy (dizziness in three and abnormal results of liver function tests in one) and one patient died during the bepridil phase. This study suggests that bepridil, 400 mg daily, is effective for the treatment of exercise-induced myocardial ischemia and angina pectoris.

Evaluation of bepridil for the treatment of angina pectoris: Evidence for preservation of left ventricular function☆

The efficacy of bepridil (400 mg once a day) was assessed in 15 patients with exertional angina pectoris. All 15 patients reported substantial clinical improvement during bepridil treatment compared with placebo treatment. Episodes of angina were 11.8 +/- 4.1 (mean +/- standard error of the mean)/week with placebo and 3.8 +/- 1.6 with bepridil (p less than 0.05); nitroglycerin use was 9.1 +/- 3.3 tablets/week with placebo and 3.5 +/- 1.7 with bepridil (p less than 0.05). Five of 15 patients receiving bepridil did not experience angina during treadmill exercise; in the remaining 10 patients, time to onset of angina during exercise was 5.7 +/- 0.9 minutes with bepridil as opposed to 4.5 +/- 0.8 minutes with placebo (p less than 0.05). Left ventricular (LV) performance at peak exercise as measured by first-pass radionuclide angiography revealed the ejection fraction to be 38 +/- 3% during placebo therapy and 47 +/- 4% during bepridil therapy (p less than 0.0025). End-diastolic LV volume was unchanged, but end-systolic volume was 136 +/- 11 and 117 +/- 13 ml (p less than 0.05) and stroke volume was 82 +/- 6 and 97 +/- 9 ml (p less than 0.05) during placebo and bepridil therapy, respectively. Heart rate at peak exercise was 136 +/- 3 beats/min with placebo and 128 +/- 3 beats/min with bepridil; however, blood pressure was unchanged. These studies demonstrate that bepridil results in significant clinical improvement and enhanced LV performance in patients with angina pectoris.

Comparison of the Cardiac and Hemodynamic Effects of Lisinopril and Atenolol in Patients with Hypertension: Therapeutic Implications

Summary The antihypertensive and hemodynamic effects of lisinopril and atenolol were evaluated in 21 patients with mild-to-moderate essential hypertension. Left ventricular systolic and diastolic performances were assessed prior to and following treatment by first-pass radionuclide cineangiography at rest and during peak upright bicycle exercise. Both lisinopril and atenolol treatment significantly reduced the blood pressure. Lisinopril therapy was associated with a reduction in systemic vascular resistance and left ventricular end-diastolic and end-systolic volumes but no change in stroke volume, cardiac output, peak ejection rate, peak filling rate, time to peak ejection rate, or time to peak filling rate. In contrast, atenolol therapy was associated with an increase in end-diastolic volume and stroke volume but no change in cardiac output; the left ventricular peak ejection and peak filling rates were decreased by atenolol treatment. Although both lisinopril and atenolol each significantly reduced the blood pressure, lisinopril had no effect on left ventricular systolic or diastolic performance; in contrast, atenolol decreased both systolic and diastolic parameters of ventricular performance. Left ventricular function may be affected in significantly different ways despite apparent similarities in blood pressure control in patients who respond to angiotensin converting enzyme inhibition or (3-adrenergic receptor blockade. Differences in hemodynamic response to an antihypertensive agent may be important in the selection of a drug for the treatment of subsets of patients with cardiac function abnormalities.

Nifedipine improves left ventricular function in patients with hypertension.

The effects of the nifedipine gastrointestinal therapeutic system (GITS) on blood pressure (BP), systemic vascular resistance(SVR), and left ventricular(LV) performance were determined in eight patients with essential hypertension. LV systolic and diastolic performancewere assessed by first-pass radionuclide cineangiography at rest and during upright bicycle exercise after initial and long-term BP reduction. After initial treatment, end-diastolic volume (LVEDV) increased in association with an increase in stroke volume (SV). cardiac output (CO), and peak ejection rate. After long-term treatment, LVEDV decreased. SV and CO returned to pretreatment values, early diastolic tilling fraction increased. and time to peak filling rate decreased. These hemodynamic changes are consistent with an initial predominant effect of vasodilation on LV function. With long-term treatment, the effects on LV diastolic performance are consistent with a positive lusitropic effect of nifedipine GITS. Nifedipine GITS is an effective agent for control of hypertension its hemodynamic effects are consistent with bothan effect on SVR due to decreased vascular smooth muscle contraction and a direct lusitropic effect on myocardial function.

Bepridil improves left ventricular performance in patients with angina pectoris

Summary Patients with coronary artery disease and angina pectoris have abnormalities of left ventricular (LV) diastolic performance. These abnormalities, which exist when the patients are at rest and not experiencing angina, are presumably secondary to abnormalities of intracellular calcium metabolism. Twenty-three patients with chronic exertional angina pectoris participated in a placebo-controlled, randomized, cross-over trial of bepridil hydrochloride. Angina frequency, nitroglycerin (NTG) consumption, and treadmill exercise capacity were assessed, and each patient underwent first-pass radionuclide cineangiography while receiving placebo or bepridil to assess LV performance. Bepridil decreased angina frequency from 8.5

Effects of antianginal therapy on left ventricular systolic and diastolic performance: Comparison of the response to bepridil, propranolol, and diltiazem

pM 0.6 to 4.4

Hemodynamic effects of a competitive renin inhibitory peptide in humans: evidence for multiple mechanisms of action.

pM 1.5 episodes per week (p < 0.01) and NTG consumption from 7.2