Atul Laddu

Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachyarrhythmias: A multicenter double-blind clinical trial

The efficacy and safety of intravenous esmolol infusion was compared to that of intravenous propranolol injection in patients with supraventricular tachyarrhythmias (SVT) in a multicenter double-blind parallel study. A total of 127 patients were randomized to either the esmolol (n = 64) or propranolol (n = 63) group. Therapeutic response was achieved in 72% of esmolol and 69% of propranolol patients (p = NS). The average dose of esmolol in responders was 115 +/- 11 micrograms/kg/min. Therapeutic response was sustained in the 4-hour maintenance period in 67% of esmolol and 58% of propranolol patients (p = NS). Rate of conversion to normal sinus rhythm was similar in the two treatment groups. After discontinuation, rapid recovery from beta blockade (decrease in heart rate reduction) was observed in esmolol patients (within 10 minutes) compared to propranolol patients (no change in heart rate up to 4.3 hours). The principal adverse effect was hypotension, reported in 23 esmolol (asymptomatic in 19) and four propranolol (asymptomatic in three) patients. In the majority of esmolol patients, hypotension resolved quickly (within 30 minutes) after esmolol was discontinued. It was concluded that esmolol was comparable in efficacy and safety to propranolol in the treatment of patients with SVT. Unlike propranolol, because of the short half-life of esmolol, rapid control of beta blockade is possible with esmolol in clinical conditions when required.

Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias

The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).

The long-term suppression of ventricular arrhythmia by oral acebutolol in patients with coronary artery disease

The short-term efficacy of oral acebutolol was evaluated in 20 patients with coronary artery disease and frequent premature ventricular contractions (PVCs) by serial 24-hour Holter monitoring before and while the patients were receiving an average daily dose of 1,100 mg. of acebutolol for four weeks. Fifty-five percent of the 20 patients showed a greater than 70% PVC reduction from baseline values. The only serious side effect during short-term therapy was mild, reversible cardiac decompensation in one patient. The long-term safety and continued efficacy of acebutolol was then evaluated over the next 11 months in nine of the 11 patients showing greater than 70% PVC reduction at four weeks. Two-thirds of these nine patients continued to show greater than 80% PVC reduction from baseline values at 12 months. One patient developed alopecia during long-term therapy. The majority of patients not responding well to acebutolol at four weeks had an actual increase in PVCs on acebutolol therapy. We conclude that acebutolol produces long-term, effective reduction in PVCs without serious toxicity in the majority of patients with ventricular ectopy. However, this drug appears to either produce an excellent response or no response with regard to PVC control in most instances.

Acebutolol therapy for ventricular arrhythmia. A randomized placebo-controlled double-blind multicenter study.

The safety and efficacy of acebutolol in suppressing ventricular ectopy was evaluated in 60 males (average age 59 years) using 24-hour Holter recordings and a double-blind, randomized, crossover protocol. Acebutolol, 200 mg and 400 mg thrice daily, was compared with placebo. Only patients who had a mean of at least 30 ventricular premature complexes (VPCs) per hour on three 24-hour control Holter recordings were included. Analysis of Holter recordings revealed greater than 70% reduction in VPCs/hour from control levels during acebutolol therapy in over 50% of the 60 patients; dose-related reduction in the mean number of single and paired VPCs and ventricular tachycardia episodes (p < 0.05) by acebutolol; and significant, asymptomatic reduction in resting heart rate and blood pressure. All side effects were transient. Acebutolol was discontinued because of side effects in one patient only.

Hemodynamic effects of esmolol, an ultrashort-acting beta blocker.

The hemodynamic effects of esmolol were evaluated in 12 male patients at rest (mean age, 51 ± 10 years) undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to esmolol), at steady state (during an intravenous infusion of esmolol 300 μg/kg/min), and at 30 minutes after stopping esmolol (postinfusion). Esmolol produced hemodynamic effects similar to the effects of other beta blockers. Significant reductions in rate‐pressure product (mean decrease, 15%), cardiac index (mean decrease, 17%), stroke volume index (mean decrease, 13%), left ventricular stroke work index (mean decrease, 20%), and left ventricular ejection fraction (mean decrease, 18%) were observed. In contrast to other beta blockers, all hemodynamic effects of esmolol had returned to baseline values within 30 minutes after the infusion stopped. One patient exhibited hypotension during the esmolol infusion; this episode resolved without sequelae after discontinuation of esmolol. In summary, the effects of esmolol at rest on hemodynamic parameters and left ventricular function are similar to other beta‐adrenergic blocking agents. Due to its ultrashort half‐life, esmolol can be administered safely in critically ill patients whose disease status makes treatment with currently available beta blockers risky.

Cardiovascular and neuromuscular effects of esmolol during induction of anesthesia.

Sixteen subjects scheduled for surgical procedures under general anesthesia participated in an investigation of the effects of esmolol on the transient hypertension and tachycardia that was observed during endotracheal intubation and on the duration of succinylcholine‐induced neuromuscular blockade. In eight subjects, infusion of esmolol was begun five minutes before induction of anesthesia and continued for 12 minutes after induction. In the remaining subjects, an equivalent volume of solvent (D5W) was infused for 12 minutes. Infusion of esmolol significantly attenuated the cardioacceleration observed during intubation without any significant effect on the pressor effects of the procedure. Esmolol delayed the recovery from succinylcholine‐induced neuromuscular blockade by less than three minutes. The mechanism of this delay remains to be investigated, although such a delay does not have clinical significance. Esmolol‐induced attenuation of the tachycardia seen during intubation may offer a protective effect on the myocardium, especially in elderly subjects and patients with coronary artery disease.

Acebutolol and left ventricular function: Assessment by radionuclide angiography

We assessed the effects of acebutolol, a cardioselective beta blocker, on global and regional left ventricular function in 26 patients with chronic angina pectoris. All patients underwent rest and maximal supine bicycle exercise radionuclide angiography while on placebo and oral acebutolol (400 mg three times a day). Resting ejection fraction on placebo was 51 ± 3% and on acebutolol was 54 ± 3% (p < 0.05). No resting ejection fraction decreased ≥7%. Only one patient (resting ejection fraction 28% on placebo and 21% on acebutolol) developed signs of fluid retention. Exercise nuclear studies on placebo revealed responses consistent with coronary artery disease (abnormal ejection fraction response to exercise and regional wall motion abnormalities) in 24 of 26 patients. Peak exercise ejection fraction was of the same order on placebo and acebutolol (51 ± 3% and 54 ± 3%, p = NS). In four patients the ejection fraction response to exercise became normal and in five patients all regional wall motion abnormalities became normal on acebutolol. Cardioselective beta blockade with acebutolol in effective antianginal doses is safe and may improve resting and exercise ventricular function.

Terazosin : a new alpha adrenoceptor blocking drug

Terazosin (Hytrin®; Abbott Laboratories, North Chicago, IL) is a new, selective alpha‐adrenoceptor blocking agent used on once‐a‐day basis for therapy of mild‐to‐moderate hypertension. Its pharmacologic properties are similar to those of prazosin. Terazosin however, differs from prazosin in that its water solubility is 25 times greater than that of prazosin and its elimination half‐life is about three times that of prazosin. Greater water solubility facilitates intravenous formulation, and longer half‐life allows once‐daily administration of terazosin. Terazosin is effective in lowering blood pressure and has a beneficial effect on plasma lipid profile. The major advantage of terazosin compared with prazosin, however, is its long duration of action. Terazosin is safe and effective when used in combination with diuretics and other antihypertensive agents, and in the long‐term treatment of patients with mild to moderate essential hypertension.

Combined terazosin and verapamil therapy in essential hypertension. Hemodynamic and pharmacokinetic interactions.

alpha-Blockers and calcium antagonists are commonly used in the treatment of hypertension, but few data are available concerning first dose or steady state (SS) hemodynamic and pharmacokinetic effects of these drugs when they are used in combination therapy. To examine these interactions, we measured supine and standing blood pressure (BP), heart rate (HR), and cardiac index (CI) for 6 h in 24 hypertensive patients after 2 weeks of placebo, again after the first dose or 3 weeks of therapy (SS) with either 120 mg verapamil (V) twice a day, or 1 mg terazosin (T) titrated weekly to 5 mg daily, and finally when T was added to V (group VT) or V added to T (group TV), acutely and at SS. Changes in supine hemodynamics when T was added to V or when V was added to T were similar and included a further reduction in BP, a transient increase in HR, and little or no change in CI. Both groups experienced significant decreases in standing blood pressure, especially 0.5 to 2 h following initiation of combination therapy despite significant increases in standing HR and CI. Standing BP tended to be lower in group TV after the first dose, but minimum standing systolic BP was not significantly different between groups (group TV 97 mm Hg at 1 h; group VT 109 mm Hg at 1.5 h, P > .05). Four patients in group TV and two in group VT experienced symptomatic orthostatic hypotension with the first dose of double-agent treatment. Pharmacokinetic interactions, including an increase in the bioavailability of T when V was added, did not correlate with the degree of orthostasis. After 3 weeks of combined therapy, the orthostatic change in BP had attenuated and symptoms had improved in all patients. We conclude that T and V represent an effective combination for the treatment of essential hypertension, but that orthostasis may result when initiating combination therapy. The orthostasis seen in some patients appears to be due to the combined vasodilatory effects rather than negative ionotropic or chronotropic effects.

Therapeutic approach to unstable angina: Nitroglycerin, heparin, and combined therapy

The term “unstable angina” is generally used to describe different clinical conditions such as accelerated angina pectoris (increase of severity and frequency of known chronic angina), angina at rest, prolonged angina associated with ST segment and T wave changes, and new onset angina. The prognosis of patients with these clinical syndromes differs considerably, with the worst prognosis for those with prolonged angina or angina at rest. Therefore management of unstable angina, including the aggressiveness and timing of interventional techniques, initially depends on the clinical presentationi Unstable angina often progresses to myocardial infarction simultaneously with the progression of an underlying thrombotic process,, Both aspirin and heparin favorably influence the clinical course of patients with unstable angina. In three large trials,2W4 aspirin has been shown to reduce mortality and protect against myocardial infarction. Utility of heparin in unstable angina. Heparin (5000 U intravenous bolus, followed by 1000 U/hr) was more effective than aspirin in relieving acute ischemic symptoms in patients with unstable angina,57 6 and was significantly more effective than placebo in preventing acute myocardial infarction in such patients.5 In one study,2 which included only patients with unstable angina, heparin was administered as a continuous infusion, with the dose adjusted to maintain the coagulation time at 1.5 to 2 times control values. Excluding the aspirin-treated patients, myocardial infarction occurred in 1 of 118 heparin