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The clinical response to enalapril in 19 cats with hypertrophic cardiomyopathy (HCM) was evaluated retrospectively. Eleven cats were in congestive heart failure (CHF) at the time enalapril was prescribed, while only one cat was in CHF when the cats were reexamined three-to-six months later. Significant changes in cardiac dimensions were identified echocardiographically. No adverse effects on blood pressure, serum creatinine, or potassium were noted. Although the preliminary data suggests that enalapril is well tolerated and may contribute to some improvements in cats with HCM, controlled, prospective studies are needed to prove the efficacy of enalapril in this disease.

THERAPEUTIC USE OF ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS: ACE inhibitors are now accepted as valuable therapeutic agents in the management of heart failure. The benefits include symptomatic relief, improvement in left ventricular function, prevention of progressive ventricular dilation, improved survival and decreased incidence of myocardial infarction and unstable angina., Potential of Angiotensin (ang) Ii Antagonists: Ang II antagonists are expected to produce similar beneficial effects to those of ACE inhibitors, through blockade of vascular, adrenal, renal and prejunctional neuronal Ang II type 1 receptors., Differences Between Ang Ii Antagonists and Ace Inhibitors: Despite similarities between ACE inhibitors and Ang II inhibitors with respect to the mechanism of action, there are theoretical differences which may be of clinical importance. Adverse effects seen with ACE inhibitors that are attributed to non-renin-angiotensin system effects (notably angioedema and cough) may be less frequent in patients treated with an Ang II antagonist. ACE inhibitors act within the renin-angiotensin system to prevent the conversion of Ang I to Ang II. Recently, however, enzymes have been described which are capable of producing Ang II via metabolic pathways independent of the classical renin-angiotensin system route., Conclusions: At the tissue level, Ang II may still be generated in a patient receiving systemic ACE inhibitor therapy. Ang II blockade at the receptor level may thus be more efficient than ACE inhibition in blocking the undesirable cardiovascular actions of Ang II.

The safety and tolerability of lisinopril have been assessed in 1,734 hypertensive patients treated with the agent in a number of clinical trials. Here we compare the clinical and laboratory adverse experiences in younger (under 55 years old) and older (at least 55 years old) patients treated with lisinopril monotherapy. The incidence of adverse experiences in these older patients was similar to that in the younger patients. A comparison also was made of clinical adverse experience data for older hypertensive patients treated either with lisinopril monotherapy or with various control agents (atenolol, metoprolol, and hydrochlorothiazide) in double-blind controlled studies. In these studies, the clinical adverse experience incidences and discontinuation percentages seen in the older patients treated with lisinopril were comparable to the data from the patients treated with the control agents. Thus, lisinopril is generally well-tolerated in older hypertensive patients, and should be considered a therapeutic option in the management of these patients.

The safety and tolerability of lisinopril were assessed in 1,476 patients [1,165 hypertensives and 311 patients with congestive heart failure (CHF)] and 211 normal volunteers. The duration of lisinopril therapy ranged from 1 day to 16 months, with a mean duration of 105 days. In the hypertensive population, the most frequent clinical adverse experiences on lisinopril alone were headache, dizziness, cough, and diarrhea. Not all of these adverse experiences were thought to be drug related. Five percent of patients were discontinued because of adverse clinical experiences; cough and dizziness were the most common reasons for discontinuation. Two of 1,165 (0.17%) hypertensive patients treated with lisinopril died, compared to 0.41% of hypertensive patients on other therapies. Neither case was considered to be drug related. In patients with CHF, the most frequent clinical adverse experiences were dizziness, diarrhea, hypotension, fatigue, headache, and rash. Not all of these adverse experiences were thought to be drug related. The percent of CHF patients discontinuing because of an adverse clinical experience was 7.4%; the most frequent causes for discontinuation were hypotension, dizziness, or renal impairment. Twelve deaths occurred in 311 CHF patients treated with lisinopril (3.9%) compared to 4/104 (3.8%) of CHF patients treated with placebo and 2/65 (3.1%) treated with captopril. Hypotension, orthostatic effects, or dizziness following the initial lisinopril dose occurred infrequently in patients treated with lisinopril. In hypertensive patients with normal renal function, including those treated previously or concomitantly with diuretic therapy, a first-dose hypotensive episode was reported in six of 955, or 0.6%. The incidence was higher (6.7%) in hypertensive patients with impaired renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart failure is a common cardiovascular disorder that increases in prevalence with age. Older patients may respond differently than younger patients to the various classes of drugs used in the treatment of congestive heart failure (CHF). The responses of older patients (at least 65 years of age) were evaluated as part of a large multicenter trial utilizing angiotensin-converting enzyme (ACE) inhibitors in the treatment of CHF. A prospectively planned subgroup analysis of older CHF patients' therapeutic response to the long-acting (approximately 24-hour) ACE inhibitor lisinopril was compared with their response to captopril, a short-acting (less than eight-hour) ACE inhibitor. Symptomatic improvement occurred in both the lisinopril and captopril groups. Exercise duration also improved for patients treated with both agents. However, there was a tendency for lisinopril to be more effective than captopril (p = 0.08). Thus, the low level of renin activity often found in the plasma of older patients did not decrease the ability of the ACE inhibitors to improve effort tolerance. Left ventricular ejection fraction increased in patients treated with lisinopril but not in those treated with captopril. The improvement in left ventricular ejection fraction with lisinopril may be indicative of a more favorable prognosis in patients with CHF, since another long-acting ACE inhibitor, enalapril, reduces the rate of mortality associated with CHF. ACE inhibitors were generally well-tolerated by the older patients in the study. Therefore, ACE inhibitors appear to offer a useful therapeutic approach to the management of CHF in the older age group.

The hemodynamic effects of varying oral doses of the long-acting converting enzyme inhibitor lisinopril were studied in an acute, single-blind, parallel fashion in 55 patients with moderate to severe congestive heart failure. Doses of 2.5, 5.0, and 10 mg produced a significant increase in cardiac index and significant reductions in pulmonary capillary wedge, right atrial, pulmonary arterial, and systemic arterial pressures and systemic vascular resistance. The changes were present up to 24 hours after dosing for most parameters. There was a clear-cut dose-response relationship observed. Forty-seven patients were followed over a 3-month period, during which functional status and exercise tolerance improved. Although 26% showed some evidence of renal dysfunction with lisinopril, these changes could be normalized by decreasing either the lisinopril or the diuretic dose. These data demonstrate that the hemodynamic changes with the long-acting converting enzyme inhibitor lisinopril can be modulated with dose adjustment in patients with congestive heart failure. They also suggest that renal function changes may be normalized by adjustment of either the dose of lisinopril or the diuretic dose.

To determine whether acute effects of the angiotensin converting enzyme inhibitor lisinopril are maintained during long-term therapy, 19 patients were studied using right-sided heart catheterization before an initial randomized dose of lisinopril and again after 12 weeks of maintenance lisinopril therapy. During initial evaluation, lisinopril produced significant decreases in mean systemic arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance, mean pulmonary arterial pressure, mean right atrial pressure and pulmonary vascular resistance, and concomitant increases in cardiac index and stroke volume index. After 12 weeks of therapy with lisinopril, the dosage of which was titrated to produce optimal relief of symptoms of congestive heart failure (CHF), repeat hemodynamic studies revealed persistent significant reductions in baseline systemic arterial pressure, pulmonary artery wedge pressure, mean pulmonary arterial pressure and systemic vascular resistance. However, the increases in cardiac index and stroke volume index were not statistically significant. To determine if further acute hemodynamic changes occur during long-term therapy, the patients were readministered a dose of lisinopril. This caused further decreases in systemic arterial pressure, mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance and mean right atrial pressure, and an increase in cardiac index. Lisinopril did not change stroke work index at either initial or rechallenge study. This study indicates that in patients with CHF treated with lisinopril, acute hemodynamic effects persist after 12 weeks of therapy, and acute hemodynamic response continues to occur upon drug readministration.

This review will discuss the safety profiles of the angiotensin-converting enzyme (ACE) inhibitors captopril, enalapril and lisinopril in patients with hypertension. In general, the safety profiles of ACE inhibitors compare favourably with those of other agents used for the treatment of hypertension. Adverse effects are not common when ACE inhibitors are used at the currently recommended doses. The adverse experiences that do occur with ACE inhibitors can be divided into 3 categories. Hypotension, hyperkalaemia and renal impairment are related directly to the blockade of the angiotensin-converting enzyme. Attention to the clinical condition, including concomitant therapy, reduces the risk of these adverse effects of ACE inhibition. Other adverse effects such as cough and angioedema also occur with all ACE inhibitors. The mechanisms are poorly understood, making it difficult to predict in which patients they will occur. Adverse effects such as rash, dysgeusia, neutropenia and proteinuria, which were reported relatively frequently in the early experience with captopril, are reported less frequently with lower doses of captopril and do not appear to be a problem with other ACE inhibitors such as enalapril and lisinopril.

1. This was a multicentre, double-blind, parallel study in 216 patients with mild to moderate (supine diastolic blood pressure = 95-115 mm Hg) essential hypertension. 2. After a 4-week placebo washout, patients were randomized to placebo or lisinopril 1.25, 5.20 or 80 mg once daily for 6 consecutive weeks. Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2, 0, 2, 4, and 6. 3. There was a linear dose-response relationship for both supine and erect blood pressure. Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups. 4. Lisinopril, at doses up to 80 mg day-1, was well tolerated.