Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.

Eye Diseases↗

PubMed1987

A comparison of enalapril and metoprolol as initial therapy for mild to moderate hypertension.

The safety and efficacy of step-one therapy with enalapril, a new angiotensin-converting enzyme inhibitor, and metoprolol were compared in a double-blind, multicenter study involving 150 patients who had mild to moderate essential hypertension. After a four-week period of placebo run-in, therapy was initiated with twice-daily administration of either 5 mg of enalapril (N = 75) or 50 mg of metoprolol (N = 75). Patients who did not achieve a supine diastolic blood pressure of less than 90 mm Hg after six weeks of enalapril (maximum dose = 40 mg/d) or metoprolol (maximum dose = 400 mg/d) had hydrochlorothiazide 50 mg/d added to their treatment regimen for an additional six weeks. Both treatments produced significant (P less than .001) mean reductions in supine and standing blood pressures after 2, 4, 6, 8, 10, and 12 weeks of active therapy. Maximum reductions from baseline values of supine blood pressure in enalapril-treated (-25/-16 mm Hg) and metoprolol-treated (-21/-15 mm Hg) patients were observed after 12 weeks of single- or double-drug therapy. Approximately two-thirds of the patients responded to single-drug therapy; when hydrochlorothiazide was added, response rates increased to 88% of the patients treated with enalapril and 80% of the patients treated with metoprolol. Enalapril produced a consistently greater reduction in systolic blood pressure. Blacks had a significantly smaller mean blood pressure response to both enalapril and metoprolol than did nonblacks. Metoprolol patients had significant mean pulse rate reductions; enalapril patients had no significant change. Four enalapril-treated and six metoprolol-treated patients discontinued treatment because of side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

A non-invasive method in the assessment of surgically created arteriovenous fistulae for uraemia.

Subcutaneous arteriovenous fistulae are constructed regularly for haemodialysis in uraemia. However there is little available data on fistula blood flow patterns. Twenty-eight radio-cephalic fistulae constructed for 18 patients were examined over a 3-month-period using range gated pulsed Doppler ultrasound. Contralateral arms were also examined. The parameters measured were mean arterial and venous diameter, mean volume flow and mean velocity flow. The values obtained from successful and failed fistulae were compared. There was no statistical difference between either arterial or venous diameter in the two groups. Mean velocity flow and mean volume flow in the successful group however did differ significantly from those that failed. Unless the values obtained at 48 h are significantly higher than the contralateral arm, then the fistula seems unlikely to succeed. It would also seem that a simple Doppler flow meter which gives reliable mean velocity flow values is sufficient for these investigations and may even be used preoperatively, resulting in fewer re-operations.

Adult↗

PubMed1987

The clinical efficacy and safety of lovastatin and MK-733--an overview.

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Dose-Response Relationship, Drug↗

PubMed1987

Enalapril and hydrochlorothiazide as antihypertensive agents in the elderly.

This randomized, double blind study compared the antihypertensive effects of enalapril to hydrochlorothiazide (HCTZ) in the elderly. One hundred seventy-four patients with diastolic blood pressures (DBP) of 90-120 mm Hg or isolated systolic hypertension (ISH) (systolic BP greater than 160 mm Hg and diastolic BP less than 90 mm Hg) were studied. After four weeks of placebo, patients received either enalapril 10 mg or HCTZ 12.5 mg once daily. If the BP was uncontrolled (DBP greater than 85 mm Hg or SBP greater than 140 mm Hg) after 4 weeks, the dose was doubled. At 8 weeks, if necessary, the other drug could be added at the lower dose, then doubled 4 weeks later. Two-thirds of the patients had essential hypertension (EH), the rest ISH; 68% were male and 80% Caucasian. The baseline BPs were 167/94 mm Hg in both groups, at 8 weeks the mean BPs were 148/85 mm Hg in both groups (p less than or equal to 0.01), and at the end of the study the BPs with enalapril were 144/83 mm Hg and with HCTZ they were 145/83 mm Hg (p less than or equal to 0.01). The Caucasians showed greater BP falls on enalapril than HCTZ after 4 weeks (p less than or equal to 0.05). The SBP falls for the ISH (-22 mm Hg) and EH (-23 mm Hg) groups were similar at the end of the study. Both drugs were generally well tolerated. Laboratory adverse experiences (AEs) were 9% more common in the HCTZ patients (n.s.). Enalapril and HCTZ both seem to be effective antihypertensive agents in the elderly.

Aged↗

PubMed1987

Enalapril: a well-tolerated and efficacious agent for the pediatric hypertensive patient.

Enalapril either alone or with a diuretic was administered to 15 children with various renal diseases and hypertension. Five were transplant recipients on multiple immunosuppressive agents. No adverse clinical or laboratory experiences were encountered except for mild proteinuria in two children, one of whom has evidence of chronic rejection. Enalapril effectively controlled blood pressure in all 15 patients when given once daily with or without food. Renal function improved in seven children. Six children are under excellent blood pressure control despite a reduction in the dose of enalapril. Two are currently on no medication, five require a diuretic, while one child is on an increased dose of enalapril.

Adolescent↗

PubMed1986

Enalapril in congestive heart failure: acute and chronic invasive hemodynamic evaluation.

Following hemodynamic evaluation using invasive and noninvasive methods, 73 patients were treated in an open, uncontrolled, multicenter study with single oral doses of enalapril maleate 1.25 to 40 mg until the optimal dose for each patient (based upon hemodynamic response) was achieved. Diuretics were withheld and reinstituted only if necessary. Hemodynamic measurements were made at 0 (predrug), 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdrug. Patients were discharged on their optimal dose, treated 1 to 4 months and then rehospitalized for repeat hemodynamic measurements. The optimal enalapril single dose was associated with the following mean peak responses: increased cardiac index 42% (SE = 6) and decreased pulmonary capillary wedge pressure 40% (SE = 3), systemic vascular resistance 39% (SE = 2), and mean arterial pressure 23% (SE = 1.5). These changes persisted during chronic therapy. Chronic treatment with enalapril also improved exercise capacity 40% (P less than 0.01), ejection fraction 18% (P less than 0.05) and clinical status (N.Y.H.A. functional class, P less than 0.01). Ten and 20 mg/day, taken as once- or twice-daily regimens, were the most commonly effective doses.

Adult↗

PubMed1986

The renal response produced by nonhypotensive sepsis in a large animal model.

We describe an animal model of generalized sepsis, induced in the sheep by cecal perforation, which reproduces the high systemic flow and peripheral vasodilation seen in early human sepsis. Despite volume loading, animals demonstrate a fall in glomerular filtration rate, oliguria, low fractional sodium excretion, maintained urine osmolarity, and increased plasma renin activity. Histologically, kidneys show no consistent abnormality; overall the findings suggest volume contraction or hypoperfusion. This is contradicted, however, by maintained blood pressure and pulmonary capillary wedge pressure, increased cardiac output, and reduced peripheral resistance. Increased Fc lysozyme and low molecular weight proteinuria suggest tubular damage. These paradoxical observations are currently unexplained.

Animals↗

PubMed1986

Enalapril: a well-tolerated and efficacious agent for the paediatric hypertensive patient.

Enalapril, either alone or with a diuretic, was administered to 14 children with various renal diseases and hypertension. Five were transplant recipients on immunosuppressive agents. No adverse clinical or laboratory experiences were encountered. Renal function improved in seven children. Normal blood pressure for age was achieved in all 14 children. However, eight children required the addition of a diuretic. In four children blood pressure remained normal despite a reduction in the dose of enalapril. Enalapril was efficacious as a once per day agent. Concomitant ingestion of food did not attenuate the blood pressure-lowering effect of enalapril.

Adolescent↗

PubMed1986

Related potential donors in renal transplantation: a high risk group for occult renal disease?

Explore the source record for details and available documents.

Adult↗

PubMed1985

[Worldwide experience with enalapril].

Up to now, the experiments carried out throughout the world with enalapril have been most encouraging. The drug gives good, even excellent responses in 54 to 66 % of patients with essential hypertension, and it is at least as effective as diuretics and beta-blockers. Compared with those of diuretics, the effects of enalapril confirm that the best responders are those patients who are most dependent on the renin-angiotensin system. When a diuretic is administered concomitantly with enalapril, almost all patients respond and the therapeutic effect is well maintained in long term. Blocadren or alpha-methyldopa can be added to hydrochlorothiazide, thus providing additional benefits to patients with severe hypertension. Enalapril reduces the undesirable metabolic effects of hydrochlorothiazide, particularly hypokalaemia. Altogether, enalapril and captopril have similar effectiveness, but enalapril is better tolerated and does not seem to produce the side-effects encountered with captopril, notably skin rashes and ageusia. As expected, enalapril and other angiotensin-converting enzyme inhibitors may be associated with azotaemia in patients with bilateral renovascular hypertension.

Captopril↗

PubMed1985

Enalapril in hypertension and congestive heart failure. Overall review of efficacy and safety.

Multiclinic controlled studies have shown that enalapril alone 10 to 40 mg/day orally is effective in lowering blood pressure in patients with essential hypertension. Enalapril has been compared with thiazides and beta-blockers (propranolol, metoprolol and atenolol). The effect on systolic blood pressure has been greater with enalapril than with beta-blockers. The proportion of patients who respond to enalapril alone with a decrease in diastolic blood pressure (greater than or equal to 10mm Hg) is around 70%. When a thiazide is added to the treatment, the proportion is above 90%. Enalapril improves the signs and symptoms associated with congestive heart failure. Patients increased their exercise tolerance by an average of 148 sec and improved in their NYHA cardiac status and prognosis classification. The overall incidence of side effects is similar to that seen in the placebo control groups. Side effects such as agranulocytosis, taste loss, rash, proteinuria were not characteristic of enalapril. This supports the hypothesis that the improved safety profile of enalapril is the result of being a nonsulphydryl angiotensin-converting enzyme (ACE) inhibitor. The most common side effects reported were dizziness, headache and asthenia. Abnormalities in electrolytes, uric acid, glucose or in lipids have generally not been associated with enalapril.

Adrenergic beta-Antagonists↗

PubMed1985

Renal and cardiovascular response to nonhypotensive sepsis in a large animal model with peritonitis.

We studied the functional effects of intraperitoneal sepsis on systemic hemodynamics in general, and on renal function in particular, in sheep in whom bacterial peritonitis was induced by cecal perforation. In the first group of seven sheep (group 1) fluid was administered throughout the period of sepsis to maintain pulmonary capillary wedge pressure as close to presepsis values as possible. These sheep exhibited hemodynamic changes known to be associated with sepsis in man: increased cardiac output and decreased systemic vascular resistance. In a second group of seven sheep (group 2) fluid intake was restricted; compared with group 1, these sheep demonstrated a smaller increase in cardiac output that did not persist and that was associated with an increase in the systemic vascular resistance during the septic period. Plasma renin levels increased fivefold in group 2 but were unchanged in group 1. Serial renal biopsies during the septic period revealed that all sheep had evidence of tubular cell damage on electron microscopy: cell swelling, loss of the microvillous brush border, and cell necrosis. Both groups of sheep also demonstrated marked tubular proteinuria similar to that found in humans with generalized sepsis. Despite this, sheep in group 1 exhibited no functional renal changes: creatinine clearance levels rose slightly from control values, urine concentrating ability was unimpaired, and fractional excretion of sodium increased appropriately in response to a sodium load. In contrast, group 2 sheep exhibited a fall in creatinine clearance levels but fractional sodium excretion did not fall as would have been expected were renal function entirely normal. The results suggest that generalized "hyperdynamic" sepsis induces tubular cell damage and tubular proteinuria by an unknown mechanism. However, this does not necessarily produce renal impairment since the glomerular filtration rate does not fall unless volume contraction is also allowed to occur.

Animals↗

PubMed1985

Acute pulmonary hypertension, leucopenia and hypoxia in early haemodialysis.

A sheep model is described which produces acute pulmonary hypertension, leucopenia and hypoxia after blood, previously placed in contact with a Cuprophan hollow fibre artificial kidney, re-enters the circulation. Relationships between these manifestations (acute pulmonary hypertension, leucopenia and hypoxia) were examined in normal leucopenic and Indomethacin pre-treated sheep. The degree of pulmonary vascular response, and severity of leucopenia and hypoxia were all directly interrelated and were dependent upon the volume of blood injected. The induction of leucopenia did not affect the pulmonary hypertension or hypoxia. Pre-treating the animals with the cyclo-oxygenase inhibitor, Indomethacin, abolished both the pulmonary hypertension and the hypoxia without any effect on the development of neutropenia. These results suggest that leucocytes do not play a role in the haemodynamic response nor in the hypoxia; activation of the cyclo-oxygenase system is necessary for the development of acute pulmonary hypertension which causes hypoxia subsequent to alterations in ventilation perfusion relationships.

Animals↗