Search PubMed⌕ Search

Biomedical subjects

J M Neutel

Publications and source records attributed to J M Neutel.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hypertension and its management: a problem in need of new treatment strategies.

Although treatments of hypertension have significantly decreased morbidity and mortality from cerebrovascular disease, the associated reductions in coronary artery disease have been very disappointing. Hypertension is a complex inherited syndrome of cardiovascular risk factors, all of which contribute to the development of heart disease. Angiotensin II receptor blockers (ARBs), such as the highly selective ARB valsartan, provide an alternative treatment strategy to address the multiple issues in coronary artery disease. These agents are well-tolerated and have a once-daily regimen that improves compliance. They bring multiple cardiovascular benefits beyond blood pressure (BP) control, such as renoprotection and cardiovascular growth reduction.

Antihypertensive Agents↗
PubMed1999

Safety and efficacy of angiotensin II receptor antagonists.

A disturbing pattern in the management of hypertension is emerging worldwide. More patients are being treated for hypertension, but blood pressures are not decreasing to target levels. Inadequate reduction in blood pressure is a risk factor for coronary artery disease. Poor drug efficacy, side effects, and lack of compliance are important factors leading to inadequate control of blood pressure. Angiotensin II receptor antagonists provide adequate 24-hour blood pressure control, as measured by ambulatory blood pressure monitoring, and have a side-effect profile similar to placebo. They also provide better patient compliance through once-daily dosing. This article compares the safety and efficacy of angiotensin II receptor antagonists with other antihypertensive agents.

Amlodipine↗
PubMed1999

Efficacy and tolerability of tasosartan, a novel angiotensin II receptor blocker: results from a 10-week, double-blind, placebo-controlled, dose-titration study. Tasosartan Investigators Group.

BACKGROUND: Angiotensin II receptor antagonists are selective blockers of the renin-angiotensin system and represent an alternative to angiotensin-converting enzyme inhibitors in the treatment of hypertension. Tasosartan is a newly developed nonpeptide AT1 receptor blocker. METHODS AND RESULTS: In this double-blind, randomized, dose-titration, multicenter trial, tasosartan and placebo were compared in patients with stage I and stage II hypertension. A prequalification washout period (antihypertensive medications withdrawn) and a 2-week qualification period (patients received single-blind placebo) preceded a 10-week, double-blind treatment period. The patients received either 50 mg tasosartan (n = 132) or placebo (n = 130) once per day and were evaluated once per week. The dose of tasosartan was increased at 3-week intervals to 100 mg and then to 200 mg if the mean sitting diastolic blood pressure (SiDBP) exceeded 90 mm Hg. Compared with placebo, tasosartan produced significantly (P <.05) greater reductions in both SiDBP (-9.4 +/- 0.7 vs -2.0 +/- 0.7 mm Hg) and sitting systolic blood pressure (SBP) (-12.2 +/- 1.2 vs +0.4 +/- 1.2 mm Hg). The rate of response (SiDBP </=90 mm Hg or a decrease from baseline of >/=10 mm Hg) was significantly (P <.05) greater in the tasosartan group than in the placebo group (55% vs 19%). The mean 24-hour blood pressure reduction with tasosartan was -12.6 +/- 0. 9/-8.1 +/- 0.6, significantly greater (P <.05) than the reduction with placebo (+0.6 +/- 0.9/+0.5 +/- 0.6 mm Hg). The trough-to-peak ratio (determined from the ambulatory data) was 0.66 for DBP and 0. 72 for SBP for the tasosartan treatment group, demonstrating 24-hour efficacy with once-a-day administration. The safety profile of tasosartan was similar to placebo. CONCLUSIONS: These results demonstrate that tasosartan at 50 to 200 mg given once a day over a titration period of 10 weeks was effective and safe in the treatment of essential hypertension.

Adult↗
PubMed1999

Comparisons of the effects of different long-acting delivery systems on the pharmacokinetics and pharmacodynamics of diltiazem.

The benzothiazepine calcium channel antagonist diltiazem is a short-acting drug. To achieve effective 24-h blood pressure control with once-daily dosing, it relies on various extended drug-delivery systems that have grown in importance as a result of the recent reports relating the use of short-acting calcium channel antagonists to increased cardiovascular morbidity. This study examines the pharmacokinetics and resulting pharmacodynamics of two different delivery systems, each loaded with 240 mg of diltiazem and administered to 40 moderately hypertensive patients in a randomized, double-blind crossover trial. After a 4-week, single-blind placebo lead-in, patients with a clinical diastolic blood pressure of > or =100 mm Hg were randomized to either the single or dual microbead diltiazem delivery system for a 4-week period. At the end of this period, each subject was evaluated with 24-h ambulatory blood pressure monitoring and subjected to 24-h inpatient pharmacokinetic analysis on separate days. This was followed by a similar 4-week period in which each subject was treated with the alternative delivery system. For diltiazem, the area under the curve for plasma concentration versus time and the maximum plasma concentration attained by the single microbead system exceeded the values achieved by the dual bead system by 15% and 25%, respectively. These differences were greatest from the 3rd through the 13th h after dosing. During this period, both systolic and diastolic ambulatory blood pressure was significantly lower when the single microbead system was used. When compared with baseline blood pressure, blood pressure reductions achieved with the single microbead system exceeded reductions achieved with the dual microbead system by at least 2 mm Hg for 10 of the 24 postdose hours. Heart rates were slightly reduced but not significantly different. This improved blood pressure control at higher plasma levels of diltiazem suggests that a more efficient delivery system could provide better blood pressure control for identical doses of diltiazem.

Adult↗
PubMed1999

Is high blood pressure a late manifestation of the hypertension syndrome?

Because hypertension has generally been defined as a disease of elevated systolic and diastolic blood pressure, the goals of treating hypertension have been simply to normalize the blood pressure. It was believed that if normal blood pressure were achieved, patients with hypertension would experience significant reductions in the incidence of associated cardiovascular events. However, studies to assess cardiovascular events in patients with hypertension have repeatedly demonstrated that reducing blood pressure results in very impressive reductions in cerebrovascular disease but in reductions of only about 16% in coronary artery disease, which is far lower than what was statistically predicted from the reductions in blood pressure. Although there are probably several reasons for the poor rate of reductions in the incidence of coronary artery disease, one of the most compelling appears to be the realization that hypertension is not simply a disease of numbers but rather a complex inherited syndrome of cardiovascular risk factors, all of which contribute to the development of heart disease in these patients. Included in the hypertension syndrome are abnormalities of lipid profile and insulin resistance, changes in renal function, endocrine changes, obesity, abnormalities of coagulation factors, and changes in the structure and function of the left ventricle and of vascular smooth muscle in the vasculature. In many patients, high blood pressure is a late manifestation of this disease process and is preceded by some or all of the associated cardiovascular risk factors. This paradigm suggests that therapeutic strategies for hypertension should be interventions that target both the hemodynamic and nonhemodynamic mechanisms of this syndrome to more completely reduce cardiovascular morbidity and mortality in patients with hypertension.

Antihypertensive Agents↗
PubMed1999

Low-dose antihypertensive combination therapy: its rationale and role in cardiovascular risk management.

Antihypertensive monotherapy, although commonly used, does not address the multifactorial nature of hypertension as a disease with many pathways. Using more than one drug makes more therapeutic sense because combination agents cover more than one pathway, yet the use of drugs in tandem is typically relegated to more problematic patients later in therapy. Many patients with hypertension are not controlled, because the monotherapeutic agent is used at its highest dose, resulting in side effects that lead to noncompliance. As opposed to fixed-dose combinations that merge two drugs at their highest doses, low-dose combination therapy provides more novel coverage of two or more metabolic pathways that contribute to hypertension. Their once-daily dosing encourages compliance. In addition, because the two drugs are combined at low doses, the probability of side effects is decreased and efficacy is often enhanced. The use of low-dose combination antihypertensive agents is a good contemporary strategy for first-line therapy in that patients can take advantage of their cardiovascular benefits and the control these agents offer early in therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Hypertension control: multifactorial contributions.

Treatment of hypertension reduces the risk of several associated deleterious conditions, although it does not lower risk for all cardiovascular diseases. A new theory suggests that high blood pressure is but one piece in the puzzle of a complex syndrome of inherited risk factors called the hypertension syndrome. Several new findings have emerged theorizing that patients may have coronary artery disease before the actual onset of elevated blood pressure. Epidemiologic studies have found that normotensive patients with a family history of hypertension often have a disease process and prognosis similar to that of hypertensives. It seems that some patients may "inherit" abnormalities that make them prone to the development of hypertension, as well as a complex series of cardiovascular disease risk factors. These include elevated lipids, increased left ventricular hypertrophy, arterial stiffening, insulin resistance, renal function abnormalities, and neuroendocrine changes. It is conceivable that the hypertension syndrome may be reversible if the disease process is diagnosed early, which appears to be well before the actual onset of high blood pressure. High blood pressure may be a risk marker for irreversible vascular disease and early detection of the many components of hypertension syndrome may delay or prevent cardiovascular disease from developing in high-risk patients.

Angiotensin Receptor Antagonists↗
PubMed1999

Comparison of telmisartan with lisinopril in patients with mild-to-moderate hypertension.

In this study, telmisartan, a new angiotensin AT ( 1 ) receptor antagonist given as monotherapy and in combination with hydrochlorothiazide (HCTZ), was compared with lisinopril as monotherapy and in combination with HCTZ. This 52-week, randomized, multicenter, double-blind, double-dummy, parallel-group, dose-titration study of 578 patients with mild-to-moderate essential hypertension (mean diastolic blood pressure [DBP], >/=95 mm Hg), compared the efficacy and safety of telmisartan (n = 385) with lisinopril (n = 193). Dosage could be increased for both telmisartan (40 --> 80 --> 160 mg) and lisinopril (10 --> 20 --> 40 mg) at each of the first 2 monthly visits if DBP control (<90 mm Hg) had not been established. Once DBP control was established, patients entered the 48-week maintenance period. During this period, the dose of the study drug was fixed, although open-label HCTZ at 12.5 mg or 25 mg was added, when needed, to regain DBP control. At the end of the titration period, DBP control was achieved on monotherapy by 67% and 63% of the telmisartan and lisinopril patients, respectively. At the end of the maintenance period, supine DBP was controlled in 83% and 87% of the telmisartan and lisinopril patients, respectively, with systolic blood pressure over DBP reductions of 23.8/16.6 mm Hg for telmisartan and 19.9/15.6 mm Hg for lisinopril. Treatment-related side effects occurred in fewer telmisartan-treated patients (28%) than in lisinopril-treated patients (40%; P =.001). Significantly fewer patients (P =.018) receiving telmisartan experienced treatment-related cough (3% v 7%), and cough led to discontinuation significantly less often (P =.007) with telmisartan treatment than with lisinopril treatment (0.3% v 3.1%). In addition, two cases of angioedema were observed, both in the lisinopril group. The selective AT (1) receptor antagonist, telmisartan, is extremely effective in the treatment of mild-to-moderate hypertension both as monotherapy and in combination with HCTZ and is at least comparable in efficacy to lisinopril, with a tolerability profile that may offer advantages in terms of a reduced incidence of adverse events.

Angioedema↗
PubMed1999

Low-dose combination therapy as first-line hypertension treatment for blacks and nonblacks.

To assess the efficacy and safety of bisoprolol/6.25-mg hydrochlorothiazide (HCTZ), amlodipine, and enalapril in black and nonblack patients, data from two comparative studies were pooled and subgroup analyses performed. Both studies had similar designs and included all three active treatments. The second study also included a placebo group. Subjects (n = 541) with a sitting diastolic blood pressure of 95-114 mmHg were titrated to achieve a diastolic blood pressure < or = 90 mmHg. The studies included 114 blacks and 427 nonblacks. Results of an intention-to-treat analysis of mean change from baseline after 12 weeks of treatment showed the following: 1) blood pressure was significantly lowered by all three active drugs compared with baseline or placebo; 2) in blacks, bisoprolol/6.25-mg HCTZ resulted in significantly greater reductions of systolic and diastolic blood pressure than enalapril or placebo, but was not significantly different from amlodipine; 3) in nonblacks, bisoprolol/6.25-mg HCTZ resulted in significantly greater reduction of diastolic blood pressure than amlodipine, enalapril, or placebo. The placebo-corrected change in blood pressure was greater for blacks than whites on the bisoprolol/6.25-mg HCTZ combination, but this was not statistically significant. Bisoprolol/6.25-mg HCTZ controlled diastolic blood pressure to < or = 90 mmHg in significantly more patients than enalapril or placebo in blacks and nonblacks. The difference in control rates was not significant versus amlodipine. The incidence of drug-related adverse events was similar between treatments; however, bisoprolol/6.25-mg HCTZ had a lower discontinuation rate due to lack of blood pressure control or adverse experiences in both blacks and nonblacks.

Aged↗
PubMed1999

What are the approaches for evaluating antihypertensive treatment by 24 h ambulatory blood pressure monitoring?

Measurements of trough blood pressure in a clinic setting have been the traditional method of assessing the efficacy of antihypertensive agents. The duration of action of antihypertensive drugs has been assessed by calculation of a trough-to-peak ratio; drugs with a trough-to-peak ratio greater than 50% are typically given once-a-day indications. However, the use of clinical measurements to assess antihypertensive agents can be misleading. Ambulatory blood pressure monitoring is a simple technique that provides accurate and reproducible data on both the efficacy and duration of action of antihypertensive agents. Although several complicated techniques have been used for the analysis of ambulatory blood pressure data, studies have demonstrated that calculation of simple blood pressure means (24 h mean, day-time mean and night-time mean) will provide all the data required to assess the efficacy of a drug. Calculations of systolic and diastolic load also provide useful information, and the index correlates closely with target-organ damage. Assessing the reduction of blood pressure during the last 2-6 h of the dosing interval provides critical information on the duration of action of agents with once-a-day dosing. Trough-to-peak ratio can also be calculated from an ambulatory blood pressure monitor. Furthermore, a simple line graph constructed from hourly means makes available, at a simple glance, a large amount of information about a drug. The reproducibility of ambulatory monitoring, together with the absence of placebo effect and the ability to exclude patients with white-coat hypertension, make the technique an extremely powerful tool for the assessment of antihypertensive agents that clearly provides more data on the efficacy and duration of action of an antihypertensive agent than do traditional clinical measurements.

Antihypertensive Agents↗
PubMed1998

Hypertension: where have we gone wrong and how can we fix it?

Hypertension is defined as a disease of elevated systolic and diastolic blood pressure and consequently the goals of treating hypertension have been simply to normalize the blood pressure. However, effective blood pressure control has not resulted in the expected decreases in coronary artery disease. These findings have forced researchers to reexamine the importance of blood pressure in causing coronary artery disease, and to pose the question "Is there more to hypertension than high blood pressure?" Although there are probably several reasons for the poor reduction in the incidence of coronary artery disease in hypertensive patients, one of the most compelling appears to be the realization that hypertension is not simply a disease of numbers, but is a complex inherited syndrome of cardiovascular risk factors, all of which contribute to heart disease in these patients. Included in the hypertension syndrome are abnormalities of lipid profile, insulin resistance, changes in renal function, endocrine changes, obesity, abnormalities of coagulation factors, left ventricular hypertrophy and diastolic dysfunction, and abnormalities of vascular structure and compliance. In many patients, high blood pressure is a late manifestation of this disease process and is preceded by some or all of the associated cardiovascular risk factors. Perhaps where we have gone wrong in the management of hypertension is in the belief that this is simply a disease of numbers. To improve our management, we need to find methods to diagnose these patients early in the course of this disease process, and to treat it as a syndrome rather than as a number.

Arteries↗
PubMed1998

Low-dose combination treatment for hypertension versus single-drug treatment-bisoprolol/hydrochlorothiazide versus amlodipine, enalapril, and placebo: combined analysis of comparative studies.

To assess the efficacy and safety of 2.5, 5, and 10 mg bisoprolol/6. 25 mg hydrochlorothiazide (HCTZ), 2.5, 5, and 10 mg amlodipine; and 5, 10, 20, and 40 mg enalapril in subjects (n = 541) with a sitting diastolic blood pressure of 95 to 114 mm Hg, data from two comparative studies were pooled. All drugs were titrated to a diastolic blood pressure 90 mm Hg or less. Both studies were double-blind, randomized, parallel dose escalation trials with similar designs and included three active treatments. The second study also had a placebo group. The mean change from baseline of systolic and diastolic blood pressure for placebo (n = 79) was -0. 1/-2.2 mm Hg; amlodipine (n = 154), -12.4/-10.3 mm Hg; enalapril (n = 155), -9.4/-8.2 mm Hg; and bisoprolol/HCTZ (n = 155), -14.0/-12.0. Overall efficacy analyses documented a statistically significant decrease in sitting diastolic blood pressure for bisoprolol/6.25 mg HCTZ compared with placebo, amlodipine, and enalapril. There was a significant reduction in sitting systolic blood pressure for bisoprolol/6.25 mg HCTZ compared with placebo and enalapril but not amlodipine. Also, there was a significant decrease in sitting heart rate for bisoprolol/6.25 mg HCTZ (-6.2 beats/min) compared with placebo (+0.1 beats/min), amlodipine (+1.2 beats/min), and enalapril (+0.5 beats/min). The control rate (diastolic blood pressure < or = 90 mm Hg) for bisoprolol/6.25 mg HCTZ (66.5%) was significantly better than for placebo (21.8%) and enalapril (47.1%) but not amlodipine (58.4%). Of those patients achieving and maintaining control, 49% of the bisoprolol/6.25 mg HCTZ subjects were on the lowest two doses compared with 30% of the amlodipine and 26% of the enalapril subjects. Percentages of patients reporting at least one drug-related adverse event through week 12 were 27%, 24%, 28%, and 25% for placebo, bisoprolol/6.25 mg HCTZ, amlodipine, and enalapril (not significant). Lower doses of two drugs in fixed combination can provide as good or better blood pressure control compared with higher doses of a single drug with similar tolerability and safety.

Amlodipine↗
PubMed1997

The circadian pattern of blood pressure: cardiovascular risk and therapeutic opportunities.

It has been known for many years that humans possess internal time clocks that regulate multiple physiologic factors (chronobiology). Epidemiologic studies have demonstrated that the peak incidence of many diseases, including respiratory disease (asthma, allergy), cardiovascular disease (hypotension, angina, myocardial infarction, stroke), as well as several others, tends to occur in a circadian pattern. In particular, studies utilizing ambulatory blood pressure monitoring have demonstrated that blood pressure has a very definite and reproducible circadian pattern over a 24-h period. Blood pressure is highest during the day; lowest during sleep, and then rapidly increases during the period 0400 h to 1200 h. Because recent data have demonstrated a possible cause-effect relationship between increases in blood pressure and angina, effective antihypertensive control in the early morning is desirable. Some once-a-day drugs taken in the morning may lose efficacy in the last few hours of the dosing interval, resulting in increases in blood pressure during the early morning period. In an attempt to ensure peak plasma levels during the early morning period, novel, controlled-onset, extended release-delivery systems have been developed. Studies using these delivery systems have demonstrated that, when dosed at night, these formulations provide maximal plasma levels during the period 0600 h to 1200 h, when blood pressure is physiologically rising at its greatest rate. The use of drugs designed to have peak efficacy at certain desirable times in the circadian pattern is referred to as chronotherapeutics.

Antihypertensive Agents↗