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D Elmfeldt

Publications and source records attributed to D Elmfeldt.

At least 37 records · Page 2Linked to original sources
PubMed1991

A population study of the pharmacokinetics of felodipine.

1. The pharmacokinetics of felodipine was studied after continuous oral administration of 5 or 10 mg conventional tablets to a population of 140 male and female Caucasian subjects, of which 67 were hypertensive patients and 73 were healthy volunteers. In addition, 42 of these individuals received felodipine intravenously. 2. With increasing age the area under the felodipine plasma concentration vs time curve (AUC), the maximum plasma concentration (Cmax), and the terminal elimination half-life of felodipine increased, while the plasma clearance of felodipine decreased. The bioavailability and steady state volume of distribution and the time to Cmax were not consistently influenced by age. 3. The ratio of the AUC of the primary pyridine metabolite of felodipine and that of unchanged drug decreased with increasing age. 4. Neither Cmax, AUC nor the half-life of felodipine were related to body mass index. 5. The distribution of AUC for felodipine, as well as the ratio of the AUC of this first metabolite to that of unchanged felodipine, was unimodal. Thus, the presence of a sizable group of individuals, with a clinically significant different metabolism of 1,4-dihydropyridine due to genetic factors is unlikely. 6. The pharmacokinetics of felodipine did not seem to differ between hypertensive patients and healthy volunteers, when adjusted for age. Neither was there a difference between patients taking beta-adrenoceptor antagonists and those who did not. 7. As a group the elderly had higher total concentrations of unchanged felodipine in plasma compared with younger individuals. The variation in plasma concentrations of felodipine between individuals is, however, only partially explained by age. In clinical practice this emphasizes the need for dose titration of felodipine.

Adult↗
PubMed1991

Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study.

The present study in hypertensive men (40-64 years old) with untreated diastolic blood pressure above 100 mm Hg was aimed at investigating whether metoprolol (n = 1,609) given as initial treatment would lower the risk for coronary events (sudden death and myocardial infarction) more effectively than thiazide diuretics (n = 1,625). A substantial part of this study was the metoprolol arm of the Heart Attack Primary Prevention in Hypertension (HAPPHY) study. The HAPPHY study was a pooling of the effect of different beta-blockers, mainly metoprolol and atenolol, in which no favorable effect in relative risk was observed for atenolol as compared with diuretics. In the present study, 255 patients suffered definite coronary events during follow-up; 25% of these events were fatal, 39% were acute myocardial infarctions, and 36% were silent myocardial infarctions. The risk for coronary events was significantly lower in patients on metoprolol than in patients on diuretics (111 versus 144 cases, p = 0.001, corresponding to 14.3 versus 18.8 cases/1,000 patient years and a relative risk of 0.76 at the end of the trial; 95% confidence interval 0.58-0.98). This difference in risk has potentially important implications for clinical practice because of the large number of hypertensive patients who are at increased risk for coronary events. Because a placebo group, for ethical reasons, could not be included, relative risk can only be expressed in relation to diuretics. There was no difference between the two treatment groups in baseline characteristics, blood pressure during follow-up, or stroke rates. Thus, the difference in risk for coronary events is probably mediated via mechanisms other than blood pressure control. However, present data might suggest that different beta-blockers may have different efficacy in preventing coronary events. The reasons for this possibility are as yet unknown.

Adult↗
PubMed1990

Felodipine in the treatment of patients with severe hypertension and impaired renal function.

Twenty-three patients with severe hypertension and impaired renal function were included in an open study of the efficacy and tolerance of felodipine treatment over 6 months. All patients were previously treated with a diuretic, a beta blocker, and a vasodilator, and eight of them also received an ACE inhibitor. At the start of felodipine treatment the previously used vasodilator was withdrawn. In nine patients the concomitant antihypertensive treatment was reduced during the study. The glomerular filtration rate (GFR), as 51Cr EDTA clearance, was determined before and at the end of the study. The blood pressure (BP) and heart rate (HR) were recorded at all clinical visits in the morning 12 hours after the evening dose of felodipine and 2 hours after the morning dose. Plasma concentrations of felodipine were measured at every visit before the morning dose and 2 hours after dose. The BP was reduced after felodipine was substituted for the previously used vasodilator. A significant additional anti-hypertensive effect was recorded 2 hours after the dose and amounted to -37 +/- 22/-15 +/- 12 mmHg (p = 0.0001/p = 0.0002) at 6 months. The effect measured 12 hours after the dose was less pronounced and was -11 +/- 28/-6 +/- 10 mmHg (p = 0.15/p = 0.03). Mean GFR was unchanged during the study, 38 +/- 19 versus 38 +/- 19 ml/min (n = 16). There was a sixfold interindividual variation in the trough plasma concentrations at steady state at the same drug dosage. Higher plasma concentrations seemed to be required to achieve the same antihypertensive effects as in patients with less severe hypertension and normal renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Plasma concentration-effect relationships of intravenous and extended-release oral felodipine in hypertensive patients.

Felodipine, a dihydropyridine calcium antagonist, was given double-blind in a crossover design comparing once-daily doses of 20 mg felodipine extended-release (ER) tablets with placebo in 12 hypertensive patients. A 2-h intravenous infusion was given after a placebo washout. After oral felodipine, blood pressure (BP) was significantly lower than after placebo, both after the first dose and after 2 weeks of treatment. Supine BP 24 h after the first dose of placebo and felodipine was 159/97 and 153/92 mm Hg (p less than 0.01/0.05), respectively. Corresponding BPs at 2 weeks were 158/99 and 144/89 mm Hg (p less than 0.01/0.01). Approximately 75% of the maximal and 60% of the trough effect at steady state were obtained already after the first dose. The plasma concentration (CpF) vs. time curve after felodipine ER was relatively flat. After oral felodipine, a linear correlation was found between BP reduction and logarithmic CpF. After intravenous administration, CpF correlated well with a hyperbolic function. These data indicate that there is an almost linear relation between BP reduction and log CpF in the range from 2-20 nmol/L, and that little additional effect is to be expected above approximately 20 nmol/L. No hysteresis was found for the relationship between CpF and BP reduction. The absolute bioavailability of felodipine ER was 22%.

Adult↗
PubMed1990

Metabolic effects of controlled-release metoprolol in hypertensive men with impaired or diabetic glucose tolerance: a comparison with atenolol.

In a double-blind, randomized, cross-over study with a single-blind placebo run-in period a new controlled-release (CR) formulation of metoprolol 200 mg once daily was compared with atenolol tablets 100 mg once daily in 22 patients (age 60.9 +/- 0.93 (SE) years) with primary hypertension and impaired or diabetic glucose tolerance. Each period lasted for three weeks. The two agents produced similar blood pressure 3 h as well as 24 h after drug intake. Three hours after drug intake, heart rate was lower on atenolol than metoprolol CR treatment, indicating a higher degree of beta-receptor blockade for atenolol at this point in time, when the plasma concentration of atenolol was most likely to be close to its peak. Concentrations of blood glucose, serum insulin, and serum C-peptide in the fasting state or after an oral glucose load did not differ between the active agents. HbA1c was marginally, but significantly, lower on atenolol than metoprolol CR treatment. No differences were found in serum levels of total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol or apoA-I, and apoB lipoproteins or triglycerides. In comparison to the placebo run-in period, both agents showed an unexpected improvement in glucose tolerance, a decrease in HDL cholesterol and for metoprolol CR a small, but significant decrease in LDL cholesterol. Thus, treatment with metoprolol CR tablets producing even plasma levels without high peak concentrations and conventional atenolol treatment had similar effects on metabolic control in hypertensive men and abnormal glucose tolerance.

Aged↗
PubMed1990

Coronary artery disease can be prevented by antihypertensive therapy: experiences from the MAPHY Study.

The present randomized primary prevention study in hypertensive men aged 40-64 years (n = 3,234) was aimed at investigating whether metoprolol given as initial treatment would prevent coronary artery disease (CAD) better than thiazide diuretics. Two hundred fifty-five patients had a definite CAD event during the 15,730 patient-years of follow-up; 25% of these events were fatal, and 38% were definite acute myocardial infarctions. The incidence of CAD was significantly lower during follow-up in patients randomized to metoprolol than in patients randomized to diuretics: 111 vs. 144 cases (p = 0.001). Stroke mortality was significantly lower in the metoprolol group than in the diuretic group, but the overall stroke incidence was similar in the two treatment groups. A majority of events occurred among smokers in both treatment groups although only one-third of patients were smokers at baseline. Blood pressure (BP) control was similar in the two treatment groups; therefore, the difference between the groups in CAD events is mediated via mechanisms other than the BP-reducing effect of metoprolol.

Adult↗
PubMed1989

Haemodynamic effects and pharmacokinetics of felodipine at rest and during exercise in hypertensive patients treated with metoprolol or atenolol.

A study has been performed in thirteen patients with essential hypertension, WHO Class I-II, and a diastolic blood pressure greater than or equal to 95 mmHg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There was no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.

Aged↗
PubMed1989

Decreased coronary heart disease in hypertensive smokers. Mortality results from the MAPHY study.

The present primary prevention study aimed at investigating whether metoprolol given as initial antihypertensive treatment would lower cardiovascular complications of high blood pressure to a greater extent than thiazide diuretics. Patients were randomized to metoprolol (n = 1,609, 8,110 patient-years) or a thiazide diuretic (n = 1,625, 8,070 patient-years). At randomization, 535 patients in the metoprolol group and 524 patients in the diuretic group were classified as smokers. Blood pressure control during follow-up was equally effective regardless of smoking habits at randomization. Cardiovascular and coronary heart disease mortality was three to four times higher in smokers than in nonsmokers, underlining the importance of smoking as a risk factor. Total and cardiovascular mortality were significantly lower for the metoprolol group than for the thiazide diuretic group in the whole study population (p = 0.028 and p = 0.012), as well as in smokers (p = 0.013 and p = 0.016). Coronary heart disease mortality was significantly lower for patients on metoprolol than for patients on diuretics in the whole study population (p = 0.048) as well as in smokers (p = 0.021). The results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of total, cardiovascular, and coronary heart disease mortality as compared with initial diuretic treatment, both in the whole study population and in smokers. The favorable effect of metoprolol must be mediated via mechanisms other than the blood pressure-lowering effect of metoprolol because equal blood pressure control was achieved with both types of medication, irrespective of smoking habits at randomization.

Adult↗
PubMed1988

Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study.

The present study of primary prevention in white men aged 40 to 64 years attempts to investigate whether a beta-blocker given as initial antihypertensive treatment would lower total mortality to a greater extent than thiazide diuretics. Patients were randomized to metoprolol (n = 1609, 8110 patient-years) or a thiazide diuretic (n = 1625, 8070 patient-years). The median follow-up time was 4.2 years. The mean dose of metoprolol was 174 mg/d, and of thiazide diuretics, 46 mg/d of hydrochlorothiazide or 4.4 mg/d of bendroflumethiazide. Identical control of blood pressure was achieved using a fixed therapeutic schedule. Total mortality was significantly lower for metoprolol than for thiazide diuretics because of fewer deaths from coronary heart disease and stroke. Total mortality was also significantly lower in smokers randomized to metoprolol. The benefit demonstrated in patients treated with metoprolol seems to have important implications for clinical practice.

Adult↗
PubMed1987

Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial.

Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to-treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent.

Adrenergic beta-Antagonists↗
PubMed1987

Antihypertensive effects and pharmacokinetics of felodipine combined with a beta-blocker and a diuretic.

The antihypertensive effect of felodipine, a new calcium antagonist with dihydropyridine structure, was investigated in 25 patients with essential hypertension that was not controlled on standard triple therapy (a beta-blocker, a diuretic, and a vasodilator). After substituting the previous vasodilator with felodipine, blood pressure was reduced and remained well controlled during a 2 year follow-up period. After about 1 1/2 years of treatment, felodipine was compared double-blind with placebo in a subgroup of 10 patients while keeping the same beta-blocker and diuretic therapy. Compared with the placebo, felodipine lowered blood pressure during a 12 h interval, which supports a twice-daily dosage in clinical practice. Determination of the plasma concentrations of felodipine during steady-state conditions showed a mean elimination half-life of 23.4 +/- 11.1 h. During long-term therapy, tolerance was good, and felodipine seems to be a safe and efficient antihypertensive agent in combination with a beta-blocker and a diuretic in patients whose hypertension is not adequately controlled on standard triple therapy.

Adrenergic beta-Antagonists↗
PubMed1987

Non-participants in a general population study of men, with special reference to social and alcoholic problems.

The bias introduced by non-participation in a study depends on the size and the composition of the non-participant group. Out of 10,000 men invited to a screening examination in a large primary prevention trial in Göteborg, Sweden, 25% did not come to the examination. The non-participants could be shown to be registered by the Board of Social Welfare for social problems and alcohol abuse to a greater extent than the participants in the study. The annual mortality among the non-participants was about twice that of the participants during the entire follow-up period of 11.8 years. The incidence of non-fatal myocardial infarction was not significantly higher in non-participants. Coronary death, on the other hand, was significantly more common among those not attending the examination (3.5 vs. 7.6%). Participants registered for alcoholic problems had coronary death rates approaching those of the non-participants. Sudden coronary death accounted for most of the excess coronary mortality. Most of the excess mortality in the non-participant group was from other causes than cardiovascular diseases and cancer but even so, about one third of the excess deaths could be attributed to coronary heart disease. Possible explanations of this excess coronary mortality include that non-participants may smoke more, more frequently have alcoholic problems and that non-participation may reflect an unwillingness to seek medical care even in the event of illness.

Aged↗
PubMed1987

Alcoholic intemperance, coronary heart disease and mortality in middle-aged Swedish men.

High alcohol consumption is one of the major risk indicators for premature death in middle-aged men. An indicator of alcohol abuse--registration with the social authorities for alcoholic problems--was used to evaluate the role of alcohol in relation to general and cause-specific mortality in a general population sample. Altogether 1,116 men (11%) out of a total population of 10,004 men were registered for alcoholic problems. Total mortality during 11.8 years' follow-up was 10.4% among the non-registered men, compared to 20.5% among men with occasional convictions for drunkenness and 29.6% among heavy abusers. Fatal cancer as a whole was not independently associated with alcohol abuse, but oropharyngeal and oesophageal cancers together were seven times more common in the alcohol-registered groups. Total coronary heart disease (CHD) was significantly and independently associated with alcohol abuse, but nearly all the excess CHD mortality among the alcohol-registered men could be attributed to sudden coronary death. Cases with definite recent myocardial infarction were not more common in the alcoholic population. A combined effect of coronary arteriosclerosis and heart muscle damage secondary to alcohol abuse is suggested. Other causes of death strongly associated with registration for alcohol abuse include pulmonary embolism, pneumonia and peptic ulcer, as well as death from liver cirrhosis and alcoholism. Of the excess mortality among alcohol-registered subjects, 20.1% could be attributed to CHD, 18.1% to violent death, 13.6% to alcoholism without another diagnosis and 11.1% to liver cirrhosis.

Alcohol Drinking↗
PubMed1987

Glucose tolerance in hypertensive patients during treatment with the calcium antagonist, felodipine.

1 Twelve non-diabetic hypertensive male patients insufficiently controlled by a diuretic were included in a double-blind, randomised study. In addition placebo or felodipine was given for 4 weeks followed by a 2 week wash-out period, after which the alternative treatment was given for another 4 weeks. At the end of each treatment period an oral glucose tolerance test (OGTT) was performed and blood pressure, plasma noradrenaline and felodipine levels were measured. 2 There was no change in either glucose, insulin or glucagon levels during the OGTT after felodipine compared with placebo. Blood pressure was significantly reduced during the dosage interval of felodipine (12 h). Plasma noradrenaline increased significantly after felodipine. Side effects were few. 3 In a separate open study 58 hypertensive patients were treated with felodipine in addition to a diuretic and a beta-adrenoceptor blocker for up to 1 year. There were no significant changes in fasting blood glucose levels during the study.

Blood Glucose↗
PubMed1987

Comparison of antihypertensive effect and pharmacokinetics of conventional and extended release felodipine tablets in patients with arterial hypertension.

In 2 separate double-blind, placebo-controlled, crossover studies, the antihypertensive effect and felodipine plasma concentrations were studied after 2 different formulations of felodipine. Both trials studied patients who had previously responded unsatisfactorily to conventional triple therapy (beta-adrenergic blocker, diuretic and vasodilator). Felodipine or corresponding placebo was added to the pre-existing beta-adrenergic blocker/diuretic combination. Both tablet formulations significantly lowered blood pressure. In patients taking plain felodipine tablets, 10mg bid for 10 days, the blood pressure reduction was evident for 12 hours but not 24 hours after each dose. At steady state, the maximal felodipine plasma concentration was 25.2 +/- 1.5 nmol/L and occurred 1.3 +/- 0.2 (range 1 to 3) hours after drug intake. When an extended release formulation of felodipine (20mg once every morning) was used, a more even plasma concentration curve was achieved. After 2 weeks' treatment, the maximal felodipine plasma concentration was 23.3 +/- 2.7 nmol/L and was reached 4.4 +/- 0.5 (range 3 to 7) hours after each dose. Systolic as well as diastolic blood pressure at steady state were reduced over 24 hours. No disturbing side effects were noted on either felodipine formulation. From these studies we conclude that oral felodipine lowers blood pressure in patients with moderate to severe hypertension when added to a beta-adrenergic blocker/diuretic combination. The extended release formulation given in a once-daily long term regimen produced a significant and equally satisfactorily controlled blood pressure reduction over 24 hours compared with the plain tablets but has the advantage of once-daily rather than twice-daily administration.

Antihypertensive Agents↗
PubMed1987

Aspects on the benefit-risk balance of felodipine in hypertension.

This review attempts to evaluate the benefit-risk balance of felodipine in the treatment of hypertension. Known positive and negative properties of felodipine are considered. Although accurate benefit-risk statements may be difficult even for old, well-established drugs it is concluded that felodipine appears to be an effective and well tolerated new antihypertensive drug. The reduction in blood pressure during felodipine treatment has been superior to that seen with established antihypertensive drugs in controlled studies.

Antihypertensive Agents↗