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Biomedical subjects

T J Cleophas

Publications and source records attributed to T J Cleophas.

At least 19 recordsLinked to original sources
PubMed1999

Combination of calcium channel blockers and beta-adrenoceptor blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Netherlands Working Group on Cardiovascular Research (WCN).

AIMS: The combination of calcium channel blockers and beta-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than beta-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced angina is preceded by increase in heart rate, calcium channel blockers with negative chronotropic properties may perform better for this purpose than nonchronotropic compounds. METHODS: A 335 patient double-blind parallel-group study comparing 14 day treatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mibefradil 50 and 100 mg added to baseline beta-adrenoceptor blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. RESULTS: Although none of the calcium channel blockers improved duration of exercise or amount of workload, all significantly delayed onset of 1 mm ST-segment depression on ETT (P<0.001 for any treatment vs baseline). In addition, mibefradil, both low and high dose treatment, produced the longest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, respectively, P<0. 003 and <0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, respectively, P<0.001 and <0.001). These effects were linearly correlated with the reduction in rate pressure product (RPP). Serious symptoms of dizziness occurred significantly more frequently on mibefradil (P<0.05), and 19 patients on mibefradil withdrew from trial. CONCLUSIONS: Calcium channel blockers with negative chronotropic properties provide greater delay of ischaemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness attenuates this benefit.

Adolescent↗
PubMed1999

Replacement of angiotensin-converting enzyme inhibitors by angiotensin-II-receptor antagonists in hypertensive patients with type II diabetes mellitus: metabolic and hemodynamic consequences.

The main pharmacodynamic difference between angiotensin-converting enzyme-inhibitors (ACE-i) and angiotensin-II-receptor antagonists (AII-r) is that ACE-i increase levels of bradykinin, which, in addition to vasodilation, may cause a decrease in insulin resistance. Hypertensive patients with diabetes type II suffering from side effects from ACE-i are frequently changed over to AII-r. The objectives of this study were (1) to study whether this procedure reduces metabolic control, (2) to study effects on blood pressure and forearm blood flow (FLOW), and (3) to study possible associations between the variables hemoglobin A (1c) (HbA(1c)) and FLOW. A self-controlled sequential comparison is required to address such questions. Sixteen patients were treated with 10 mg enalapril or equipotent doses of other ACE-i for 6 months and subsequently with the AII-r losartan at 50 mg daily for 6 more months. Patients were examined at the outpatient clinic every 4 to 8 weeks during the trial. FLOW was measured by iridium strain gauge venous occlusion plethysmography. Mean arterial pressure (MAP) increased by 4 +/- 5 mm Hg (P <.05) after 6 months of losartan treatment as compared with the point of withdrawal of ACE-i. FLOW decreased by 5.4 +/- 5.0 mL/100 mL tissue/min (P <.001), and HbA (1c) increased by 0.6 +/- 0.8 mmol/L (P <.05). Other metabolic variables, including cholesterol, high-density lipoprotein cholesterol, and triglycerides, were not significantly influenced by the change in therapy. Multiple regression analysis revealed that after adjustment for difference in HbA (1c), the correlation between FLOW and MAP was unchanged, and after adjustment for difference in FLOW, the correlation between HbA (1c) and MAP was no longer significant. Replacement of ACE-i by AII-r in hypertensive patients with type II diabetes mellitus induced a significant increase in HbA (1c) and MAP and a decrease in FLOW. The associations of HbA (1c) and FLOW with MAP were at least partly independent of each other, suggesting that mechanisms other than the bradykinin system (eg, the angiotensin (2) -receptor system) are involved. Our study design did not control for placebo and time effects, and so the data are of a preliminary nature.

Adult↗
PubMed1999

Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN).

The combination of calcium channel blockers and beta blockers is more effective for the treatment of exercise-induced angina pectoris than beta blocker monotherapy. Since ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 and 10 mg, diltiazem XR 200 and 300 mg, and mibefradil 50 and 100 mg treatment added to baseline beta blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. Although none of the calcium channel blockers improved duration of exercise or amount of workload, all of them significantly delayed onset of 1 mm ST segment depression on ETT (p<0.001 for any treatment versus baseline). In addition, mibefradil, both low- and high-dose treatment, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, p<0.003 and <0.001, respectively; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, p<0.001 and <0.001, respectively). These effects were linearly correlated to the amount of rate pressure product (RPP) reduction. Serious symptoms of dizziness likewise occurred significantly more frequently with mibefradil (p<0.05) and led 19 patients taking mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with negative chronotropic property provide better delay of ischemia in patients with exercise-induced angina but that the concomitant risk of intolerable dizziness largely reduces this benefit.

Adolescent↗
PubMed1999

Combination of calcium channel blockers and beta-blockers for patients with exercise-induced angina pectoris: beneficial effect of calcium channel blockers largely determined by their effect on heart rate.

The combination of calcium channel blockers and beta-blockers is more effective for the treatment of exercise-induced angina pectoris than beta-blocker monotherapy. As ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with a negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 mg and 10 mg, diltiazem 200 mg and 300 mg, and mibefradil 50 mg and 100 mg treatment added to baseline beta-blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. All of the calcium channels blockers significantly delayed the onset of 1 mm ST-segment depression on ETT (p < 0.001 for any treatment vs. baseline). In addition, mibefradil, in both low- and high-dose treatments, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 seconds, respectively, p < 0.003 and < 0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 seconds, respectively, p < 0.001 and < 0.001). A stepwise logistic regression analysis revealed that this beneficial effect of calcium channel blockers was largely dependent on their effect on heart rate. Serious symptoms of dizziness likewise occurred significantly more frequently on mibefradil (p < 0.05 vs. diltiazem) and urged no fewer than 19 patients on mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with a negative chronotropic property provide a better delay of ischemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness may reduce this benefit.

Adolescent↗
PubMed1999

Is selective reporting of clinical research unethical as well as unscientific?

BACKGROUND: Studies that do not confirm their prior hypotheses, otherwise called "negative" studies, receive less interest from different parties including authors, editors and sponsors, and so, not to publish such studies is a common phenomenon. Opinions differ on whether or not this phenomenon introduces imprecision into the assessment of health research and care. OBJECTIVE: The current paper gives arguments against and in favor of publishing "negative" trials, and tries to give suggestions for a more balanced approach to this problem. RESULTS: Arguments against publishing "negative" trials include: we need not publish erroneously "negative" trials; we need not publish a "negative" study out of worry that the favored treatment is inferior; full-length reports of "negative" trials devaluate the quality of literature, because the data are usually not so important, and generally receive little interest from readers, and so, not to publish them is a more or less "natural" matter of course. Arguments in favor of publishing "negative" trials include: no report reduces the flow of information because "negative" trials provide at least some evidence and balance against the overwhelming power of positive data readily accepted for publication; no report violates the promise to patient participants; studies that do not confirm prior hypotheses are especially important; not-publishing leads to unnecessary repetition of research. Initially, trials were frequently "negative" not only due to lack of power but also due to inappropriate hypotheses and poor designs. Currently, this is less so, and the issue of selective reporting, therefore, needs to be reassessed. Suggestions for a more balanced approach to the problem of selective reporting might include: careful planning before the trial begins, reduces the chance of biased and erroneously "negative" trials; any trial, "positive" or "negative", provides probabilities rather than truths; this notion does not explain away publication bias but does make it less of a problem; "negative" trials may not be appropriate for general journals but very relevant to specialist journals as well as other organs of specialist groups; ethical committees and trial review boards should address the issue of publishing as part of their function. CONCLUSION: Data from properly executed trials should routinely be made available. However, we should not forget that the empirical observations provided by clinical trials, are statistically tested, and that statistics are based merely on probabilities. It means that we must consider a more philosophical attitude to clinical trial evidence in terms of acceptance that scientific truths are rarely absolute.

Clinical Trials as Topic↗
PubMed1998

A randomized, placebo-controlled study of loop diuretics in patients with essential hypertension: the bumetanide and furosemide on lipid profile (BUFUL) clinical study report.

This study was conducted to determine whether loop diuretics are more effective than placebo in reducing blood pressure without raising serum lipid levels, and whether bumetanide is more effective than furosemide in this respect. In a double-blind, 24-week placebo-controlled crossover study, 27 patients with essential hypertension were treated in four periods of 6 weeks each, including placebo twice, furosemide 40 mg daily, and bumetanide 1 mg daily. Several metabolic parameters, including serum lipid levels, and blood pressure were assessed. Overall levels of total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were 5%, 12.4%, and 4.8% higher, respectively, during loop diuretic therapy than during placebo treatment. Overall systolic and diastolic blood pressure measurements were 12 mmHg and 4 mmHg lower, respectively, during loop diuretic therapy than during placebo treatment. Any added effect of bumetanide on serum lipid levels and blood pressure compared with furosemide, however, could not be confirmed. Our results indicate that the loop diuretics bumetanide and furosemide are effective in reducing blood pressure, and influence serum lipid levels markedly less than do thiazide diuretics or chlorthalidone. In addition, these results indicate that differences in blood pressure reduction and serum lipid levels between the two compounds were small and nonsignificant.

Adult↗
PubMed1998

Depression and myocardial infarction: implications for medical prognosis and options for treatment.

Mental depression and myocardial infarction (MI) are closely related. The current paper reviews pathophysiological mechanisms that could link depression to MI and discusses the pros and cons of different pharmacological and non-pharmacological treatment modalities that could be considered. The selective serotonin reuptake inhibitors lack arrhythmogenic effects, and have a beneficial effect in addition to depression on psychological factors, such as anxiety and mood disturbances, which are not uncommon in post-MI patients. Studies to further determine the impact of depression on the outcome of MI, and the place of different treatment modalities are in progress.

Antidepressive Agents↗
PubMed1998

Crossover studies are a better format for comparing equivalent treatments than parallel-group studies.

BACKGROUND: In controlled clinical trials the new treatment may be a slight modification of the standard or be equivalent to it with the addition of a new component. In this situation there is a positive correlation between the response to the new and the standard treatment. OBJECTIVE: The influence of the correlation between the treatment responses on the statistical sensitivity of testing was studied. Randomized trials of equivalent treatments in psychiatry and hypertension research were studied for their design in relation to their level of correlation. RESULTS: With equivalent treatments and, thus, a positive correlation a paired analysis provides better power than an unpaired one. CONCLUSIONS: Crossover studies are a better format than parallel-group studies for comparing equivalent treatments. The scientific community is technically largely unaware of the mechanisms by which correlation levels influence or lack to influence the statistical power of controlled clinical trials.

Adrenergic alpha-Antagonists↗
PubMed1998

Mechanisms offsetting the beneficial effects of antihypertensive drugs: a problem increasingly considered but incompletely understood.

In clinical practice it is far from uncommon that antihypertensive drugs fail to meet their expectations. This is mainly due to mechanisms counteracting their antihypertensive effects. These mechanisms include stimulation of the sympathetic nervous system (SNS), inhibition of the parasympathetic nervous system (PSNS), stimulation of the renin-angiotensin-aldosterone system (RAAS), as well as endothelium-dependent mechanisms. To review whether the activation of such mechanisms follows differential patterns depending on the type of antihypertensive therapy being used. The antihypertensive effects of diuretics and calcium channel blockers are largely offset by all of the mechanisms enumerated. The antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II (AII) receptor antagonists and beta-blockers are counteracted by all of the mechanisms enumerated except for the effects of a stimulated RAAS and SNS, respectively. ACE inhibitors/AII receptor antagonists and beta-blockers display a better profile of mechanisms counteracting their antihypertensive effects than other categories of drugs currently available. However, because this is not routinely confirmed by random trial evidence, additional determinants of drug performance must be considered including between-subject disparities in drug response, metabolic effects, and proliferative effects.

Adrenergic beta-Antagonists↗
PubMed1998

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin.

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published. The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms. Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded. The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime. In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02). Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be.

Adult↗
PubMed1998

Low molecular weight heparins better than unfractionated heparin in unstable coronary artery disease? Unstable angina pectoris/non-Q wave infarction a partly outpatient clinic condition?

Important theoretical advantages of low molecular weight heparins compared to standard heparin include better inactivation of the coagulation mechanism as well as better bioavailability and pharmacokinetic properties. In patients with unstable angina pectoris/non-Q wave infarction these advantages may translate into a reduced combined risk of death, myocardial infarction, and recurrent angina as well as a reduced risk of bleeding, although data so far are limited. Data on quality of life, cost analysis, and patient compliance are missing. The initial benefit of both heparin and low molecular weight heparins are partly lost after withdrawal of therapy. The simple dosage regimen of low molecular weight heparins would, however, enable to continue therapy for longer periods of time. Long-term trials are in progress to further elucidate this important issue. The simple dosage regimen also would enable earlier discharge from hospital which would unburden crowded clinical departments and might contribute to patients' quality of life.

Angina, Unstable↗
PubMed1997

Quality of life before and during antihypertensive treatment: a comparative study of celiprolol and atenolol.

Hypertensive patients may be adversely affected by complications and other concomitant processes such as anxiety, sedation, and drug side effects. It has been suggested that some recently developed antihypertensive agents do not affect quality of life by causing adverse effects. We compared the effects of two antihypertensive drugs on quality of life: atenolol, a standard cardioselective beta-blocker, and celiprolol, one of a new class of selective beta-blockers with vasodilatory properties. One hundred thirty-two patients with mild-to-moderate hypertension were eligible to enter a 28-week, double-blind, parallel-group study. The study protocol consisted of a 4-week period on placebo and a 24-week period of dosage-adjusted treatment with either atenolol or celiprolol. We assessed both systolic and diastolic blood pressure and quality of life perception by a selected test battery that included the Bulpitt and Fletcher Quality of Life Questionnaire. Supine blood pressure fell from 167/101 (range 120/95 to 200/116) to 150/92 mm Hg (p < 0. 0001) during celiprolol treatment. This antihypertensive effect was at least as good with celiprolol as with atenolol. Quality of life perception was comparable for the two drugs although adverse effects were seen more frequently with atenolol than with celiprolol, particularly after prolonged treatment. Patient compliance was better for celiprolol than for atenolol. Our results show that the selective beta-blocker with vasodilatory property celiprolol is at least as effective as atenolol and that it is more advantageous in terms of some quality of life variables.

Adult↗