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Biomedical subjects

D T Nash

Publications and source records attributed to D T Nash.

At least 19 recordsLinked to original sources
PubMed1994

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up.

The Expanded Clinical Evaluation of Lovastatin study, a randomized, double-blind, placebo- and diet-controlled multicenter trial, evaluated the efficacy and tolerability of lovastatin over 48 weeks in 8,245 patients with moderately severe hypercholesterolemia. During year 1 of follow-up of the full cohort, lovastatin at 20 or 40 mg/day, or 20 or 40 mg twice daily, produced dose-dependent decreases in low-density lipoprotein (LDL) cholesterol (24% to 40%) and triglyceride levels (10% to 19%), and increases in high-density lipoprotein (HDL) cholesterol (6.6% to 9.5%). In all, 977 patients continued their original blinded treatment for an additional year. In year 2, the LDL cholesterol response to lovastatin was maintained, the triglyceride reductions were somewhat less, and the increases in HDL cholesterol were moderately greater than in year 1. Successive transaminase elevations > 3 times the upper limit of normal were observed in only 1 patient in year 2, yielding a cumulative 2-year incidence of from 0.1% (placebo or lovastatin 20 mg/day) to 1.9% (lovastatin 80 mg/day). Myopathy occurred in only 1 patient during year 2, and over the 2-year study was observed rarely and only at lovastatin dosages of 40 and 80 mg/day. This study indicates that lovastatin maintains its efficacy over long-term follow-up, particularly in effectively lowering LDL cholesterol, is generally well tolerated, and has a favorable safety profile.

Alanine Transaminase↗
PubMed1992

Comparative properties of angiotensin-converting enzyme inhibitors: relations with inhibition of tissue angiotensin-converting enzyme and potential clinical implications.

This review summarizes the evidence indicating that local synthesis of angiotensin II, and interference with this process by inhibition of angiotensin-converting enzyme (ACE), may be important in the treatment of hypertension. Inhibition of tissue converting enzyme generally has a stronger correlation with the hemodynamic effects of ACE inhibitors than inhibition of ACE in plasma. Reported differences in the ability of ACE inhibitors to penetrate tissues and to bind to the converting enzyme may be closely related to the relative lipophilicity of these agents. Finally, correlation of data from clinical studies with results provided by laboratory experimentation suggests that the efficacy of different ACE inhibitors in hypertensive patients may be predicted from differences among the actions of these drugs in vitro and in whole animals.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. Effect of patient characteristics on lovastatin-induced changes in plasma concentrations of lipids and lipoproteins.

BACKGROUND: Lovastatin produces consistent dose-related reductions in plasma levels of low density lipoprotein (LDL) cholesterol along with variable decreases in triglycerides and increases in high density lipoprotein (HDL) cholesterol. Patient characteristics from the Expanded Clinical Evaluation of Lovastatin (EXCEL) study were examined to determine their association with the magnitude of lovastatin-induced changes in these lipids and lipoproteins. METHODS AND RESULTS: After a baseline period consisting of dietary therapy, 8,245 patients with moderate hypercholesterolemia were randomized to five groups that received 48 weeks of treatment with either placebo or daily doses of lovastatin ranging from 20 to 80 mg. By use of linear statistical models, 20 different patient characteristics were examined for modification of the dose-dependent responses observed. For LDL cholesterol, the following were associated with enhanced lowering (p less than 0.05; percent changes are placebo-corrected, adjusted mean changes from baseline for the 80-mg/day lovastatin group): full drug compliance (-41.9%) versus 80% compliance (-20.3%); an age of 65 (-43.4%) versus 45 years (-38.1%) for women; white race (-40.9%) versus black race (-38.0%); and 4.5-kg weight gain (-42.6%) versus 4.5-kg weight loss (-37.9%). Similar relations for enhanced triglyceride lowering were found with older age and weight gain. Patients with initially low HDL cholesterol (less than 0.91 mmol/l) and high triglycerides (greater than 2.26 mmol/l) had enhanced responses for these parameters: placebo-corrected percent changes at 80 mg/day were -27.4% for triglycerides and +12.3% for HDL cholesterol. CONCLUSIONS: Overall, patient characteristics had very little impact of clinical importance on the dose-dependent LDL cholesterol lowering found with lovastatin. In patients with initially high levels of triglycerides and low levels of HDL cholesterol, the elevation of HDL cholesterol produced by lovastatin appears to be enhanced.

Cholesterol, HDL↗
PubMed1991

Expanded clinical evaluation of lovastatin (EXCEL) study results: III. Efficacy in modifying lipoproteins and implications for managing patients with moderate hypercholesterolemia.

In the multicenter, double-blind EXCEL (Expanded Clinical Evaluation of Lovastatin) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated. Patients were randomly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day, or 20 or 40 mg twice a day. At all of these dosages, lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein (LDL)-cholesterol levels, averaging 24% (20 mg/day) to 40% (80 mg/day). The magnitude of the effect of this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program (NCEP) goals. In the absence of coronary artery disease (CAD) or two other CAD risk factors, the LDL-cholesterol goal of 4.14 mmol/L (160 mg/dL) was attained by 22% of patients in the placebo group and between 81% (20 mg/day) and 96% (80 mg/day) of those treated with lovastatin. For those with CAD or at least two other CAD risk factors, the LDL-cholesterol goal of 3.36 mmol/L (130 mg/dL) was attained by 4% of placebo patients and between 38% (20 mg/day) and 83% (80 mg/day) of those treated with lovastatin. Lovastatin also increased high-density-lipoprotein cholesterol (7-10%) and decreased triglycerides (10-19%) in a dose-dependent manner. Thus, when used as an adjunct to a prudent diet, lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia.

Cholesterol, HDL↗
PubMed1991

Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin.

This randomized, double-blind, multicenter, diet-and-placebo-controlled study was designed to clarify the dose-response relationship of lovastatin therapy to lipid-modifying efficacy and drug-related adverse events. Exclusion criteria were minimized so that study patients were representative of the majority of patients with moderate hypercholesterolemia seen in medical practice. After 6 weeks on the American Heart Association Step 1 Diet, a total of 8,245 patients were randomly assigned to 48 weeks of treatment with diet and placebo or lovastatin at dosages of 20 or 40 mg once a day or 20 or 40 mg twice a day. All adverse events were monitored, with particular attention to evaluation of liver and muscle. Liver transaminase elevations suggestive of possible hepatotoxicity, defined as successive elevations in either aspartate transaminase or alanine aminotransferase greater than 3 times the upper limit of normal, occurred in equal numbers of placebo and lovastatin 20 mg/day treated patients (0.1%). The frequencies were higher in lovastatin 40 mg/day and 80 mg/day patient groups (0.9 and 1.5%, respectively). No patient was diagnosed as having clinically symptomatic hepatic dysfunction. Creatinine kinase (CK) elevations above the upper limit of normal occurred frequently in placebo- (29%), as well as lovastatin-treated patients (29-35%), and muscle symptoms were reported with similar frequency in all groups (7-9%). The combination of muscle symptoms with marked CK elevations (greater than 10 times the upper limit of normal) was seen in only five patients: one in a 40 mg/day dose group and four in the 80 mg/day dose group. No patient developed rhabdomyolysis. The incidence of clinical and laboratory adverse events requiring discontinuation was 6% for the placebo group and from 7% (20 mg/day) to 9% (80 mg/day) for lovastatin treatment groups. No new types of adverse experiences related to lovastatin treatment were reported. Lovastatin, as an adjunct to diet for the reduction of elevated LDL cholesterol, was generally very well tolerated.

Alanine Transaminase↗
PubMed1990

Lowering cholesterol naturally.

Patients today are more likely than ever to seek advice about reducing cholesterol levels. Physicians can help by teaching patients how to cut down on saturated fats. However, as Dr. Nash points out, eating habits are difficult to change, especially for those who think that healthy foods have an unpleasant taste. This article discusses several dietary interventions that have been proven to reduce cholesterol levels and thus the risk of coronary artery disease.

Cholesterol↗
PubMed1990

Alpha-adrenergic blockers: mechanism of action, blood pressure control, and effects of lipoprotein metabolism.

The sympathetic nervous system plays a major role in the pathogenesis of essential hypertension and is mediated by the alpha and beta receptors. The alpha receptor is divided into two types, alpha 1 and alpha 2, based on response to epinephrine and norepinephrine. alpha 1-Adrenergic receptors have a high affinity for drugs such as prazosin, doxazosin, and terazosin, which act to reduce blood pressure by selective blockade of the receptor. These agents provide a rational approach to the treatment of hypertension by correcting elevated total peripheral resistance, the fundamental hemodynamic abnormality in essential hypertension. In contrast, early alpha-adrenergic receptor blockers nonselectively blocked both alpha 1 and alpha 2 receptors and were unsuitable as antihypertensive agents because they induced tachycardia and patients developed a tolerance to them rapidly. alpha 1-Adrenergic blockers also have beneficial effects on plasma lipoproteins, tending to decrease levels of triglycerides and cholesterol and increase levels of high-density lipoprotein (HDL) cholesterol and the HDL cholesterol/total cholesterol ratio. beta-Adrenergic blockers, such as propranolol and atenolol, have been shown to have an adverse effect on the lipid profile by tending to increase levels of triglycerides and decrease HDL cholesterol. A number of mechanisms contribute to these effects, in particular, adrenergic modulation of lipoprotein lipase and the triglyceride secretion rate. Doxazosin has been shown to increase the activity of LDL receptors, which may be partly responsible for its beneficial effect on plasma lipids and lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1989

Risk factor knowledge, status, and change in a community screening project.

This report describes a community-based cardiovascular risk-reduction program which targeted high-risk individuals. A total of 1,471 individuals participated and were screened for blood pressure, fasting serum cholesterol, blood glucose level, and appearance of the serum. These individuals also completed a questionnaire regarding their knowledge of heart disease. Overall, 522 (35.5%) individuals had a cholesterol level of 240+ mg/dl; 261 (17.7%) had hypertension; 118 (8%) had a glucose level of 120+ mg/100 ml blood; 266 (18.1%) smoked; and the serum was evaluated as "turbid" or "lipemic" in 105 (7.1%). Therefore, of the 1,471 individuals examined, 733 (49.8%) could be considered "at risk" due to the presence of one or more risk factors. Interestingly, 73% of respondents knew their blood pressure, whereas only 15% and 12%, respectively, knew their cholesterol and glucose levels. Eighty percent of the sample knew that smoking, hypertension, and cholesterol were risk factors, but only 50% of the sample identified diabetes as an independent risk factor. Contrary to expectation, knowledge of heart disease and diabetes was not related to either initial level or change in cholesterol at 18-month retest. Overall, these results indicate that a community screening program can identify high risk individuals at a relatively low cost, and that knowledge of risk factors and disease is not related to initial risk status or self-initiated change in risk status.

Adolescent↗
PubMed1988

Long-term efficacy and safety of nitrendipine in severe essential hypertension.

This multicenter study evaluated nitrendipine, a dihydropyridine calcium antagonist, alone or in combination with hydrochlorothiazide and/or propranolol in severe essential hypertension (baseline supine diastolic BP greater than or equal to 115 mm Hg). After an initial 3- to 7-day drug-free run-in, a 2- to 5-week titration phase, and a 4- to 6-week maintenance period, patients with supine diastolic less than or equal to 90 mm Hg entered long-term maintenance. Four centers enrolled 57 patients initially; 43 qualified for the extended therapy trial, and 30 had completed greater than 2 years of therapy (mean duration of 756 days) at the time of analysis. Supine BP fell from 186/122 +/- 5/2 mm Hg at baseline (group mean +/- SEM) to 139/89 +/- 3/2 mm Hg after 2 years (p less than 0.001/0.001). Standing BP fell from 185/126 +/- 5/2 to 138/90 +/- 3/2 mm Hg (p less than 0.001/0.001). Supine pulse rate changed from 82 beats/min at baseline to 74 beats/min (p less than 0.01) and standing pulse rate from 88 to 78 beats/min (p less than 0.01). Seventeen patients received nitrendipine alone, 4 received nitredipine plus HCTZ, 2 received nitrendipine plus propranolol, and 7 patients received all three drugs. Response was similar in patients less than 50 years old and in those greater than or equal to 50 years, and also in black and nonblack patients. Three patients were lost to follow-up, six were terminated for inadequate BP control, and four terminated for side effects. Twenty-four patients completed greater than 2.5 years treatment (mean duration of 933 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

A double-blind parallel trial to assess the efficacy of doxazosin, atenolol and placebo in patients with mild to moderate systemic hypertension.

The antihypertensive and lipid effects of doxazosin and atenolol were compared in a 10-week, double-blind, parallel, placebo-controlled study. The 129 adults enrolled had mild to moderate hypertension (average supine diastolic blood pressures for doxazosin, atenolol and placebo were 100.6, 101.0 and 99.7 mm Hg, respectively). Patients were randomly assigned to treatment with doxazosin, 1 to 16 mg daily, atenolol, 50 to 100 mg daily or placebo. Among 114 patients included in the efficacy analysis, standing blood pressure (systolic/diastolic) changed by -13/-11 mm Hg with doxazosin (n = 37), -12/-12 mm Hg with atenolol (n = 39) and +1/-1 mm Hg with placebo (n = 38). Mean reductions in blood pressure for doxazosin and atenolol were significantly greater than those for placebo (p less than 0.01), although no statistically significant differences between the active agents were noted. Serum lipid measurements were evaluable for 116 patients, and the 38 doxazosin-treated patients in this group experienced reductions in total cholesterol, total triglyceride and very low density lipoprotein cholesterol levels. Both doxazosin and atenolol demonstrated comparable acceptance profiles. Doxazosin is an effective hypotensive agent with beneficial effects on serum lipid levels.

Adrenergic alpha-Antagonists↗
PubMed1987

Controlled multicenter study of the antihypertensive effects of lisinopril, hydrochlorothiazide, and lisinopril plus hydrochlorothiazide in the treatment of 394 patients with mild to moderate essential hypertension.

Lisinopril (LIS) is a lysine analog of enalaprilat, the active metabolite of enalapril, an angiotensin-converting enzyme inhibitor (ACEI). Unlike enalapril, the precursor of enalaprilat, LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration. Short-term (12 weeks) and long-term (24 weeks) blood pressure control has been studied with LIS, hydrochlorothiazide (HCTZ), and LIS + HCTZ when given once a day. Drug treatment had three phases: (i) 2-4 weeks of single-blind placebo washout; (ii) 12 weeks of double-blind comparison therapy with LIS 20, 40, and 80 mg vs. HCTZ 12.5, 25, and 50 mg, vs. LIS + HCTZ 20 + 12.5, 40 + 25, and 80 + 50 mg; (iii) 13-24 weeks single-blind LIS vs. LIS + HCTZ. Starting double-blind therapy at the lowest dose, all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP (SDBP) less than 90 mm Hg. At the end of 12 weeks of double-blind therapy, uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped. Mean BP reductions (systolic/diastolic, mm Hg) for all three groups after 12 weeks of double-blind comparison therapy were: (i) LIS (n = 162), -16.6/-12.5; (ii) HCTZ (n = 155), -10.4/-6.8; (iii) LIS + HCTZ (n = 74), -23.9/-18.2 with p less than 0.01 for all groups compared to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗