| 1. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Addition of the calcium antagonist PN 200-110 to pindolol markedly augments the antihypertensive effect in essential hypertension.
- 1987
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 10 Suppl 10
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Tidskriftsartikel (refereegranskat)abstract
- Several large-scale studies have recently drawn attention to the fact that arterial hypertension frequently is inadequately controlled and that therapeutic alternatives other than the commonly employed stepped-care treatment may be needed in order to obtain normotension. For this reason PN 200-110, a new dihydropyridine calcium antagonist--at two different dose levels (average 3.8 mg b.i.d. or 5.7 mg b.i.d.)--or placebo was added in a double-blind cross-over trial to pindolol, 10 mg per day, in 20 patients with essential hypertension, after an initial 3-week placebo period. Ionized calcium in serum was determined repeatedly during the study. From an initial level of 157/100 mm Hg, PN 200-110 at the first dose level reduced blood pressure by 14/11 mm Hg (p less than 0.01/0.001) and at the second dose level reduced blood pressure by 22/18 mm Hg (p less than 0.001/0.001). The reduction in mean arterial pressure was significantly correlated to age (=0.050, p less than 0.05). There was no significant increase in heart rate, nor were there any significant correlations between ionized calcium and the effect of PN 200-110 nor between the changes in ionized calcium and the changes in blood pressure. Adverse effects were few and mild. One patient had to be withdrawn because of side effects, probably not related to the investigated drugs. Thus, addition of PN 200-110 to hypertensive patients treated with pindolol caused highly significant and clinically relevant further reductions in arterial pressure. The results show that a combination of this kind offers the possibility of good blood pressure control.
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| 2. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Calcium antagonists combined with beta-blockers or ACE inhibitors in the treatment of hypertension.
- 1988
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Ingår i: Journal of cardiovascular pharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0160-2446. ; 12 Suppl 6
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Tidskriftsartikel (refereegranskat)abstract
- During the last few years, there has been a growing awareness that treated hypertensive patients are still at substantially increased risks for cardiovascular morbidity and mortality and that one conceivable explanation for this is that their blood pressure has not been lowered to strictly normotensive levels. To obtain normotensive blood pressures, it may be necessary to skillfully combine antihypertensive drugs much more frequently than has been common so far. In this context, calcium antagonists in combination with beta-blockers are of special interest, since several controlled studies have shown that a combination between a beta-blocker and nifedipine, nitrendipine, isradipine, or felodipine have been remarkably potent as regards their antihypertensive effect. In controlled trials, such combinations have also been shown to be more effective and better tolerated than a combination between a beta-blocker and hydralazine. Marked efficacy has also been noted when a calcium antagonist has been combined with an angiotensin converting enzyme (ACE) inhibitor. So far, most studies have dealt with small numbers of patients and study design has not always been optimal. Results from controlled studies will presumably be ready for presentation in the near future. It can be concluded that combination therapy between calcium antagonists and beta-blockers or ACE inhibitors appear to be markedly effective and well tolerated. This would offer the possibility of reducing elevated arterial pressure to normotensive levels in many hypertensive patients.
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| 3. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Potentiation of the antihypertensive effect of enalapril by randomized addition of different doses of hydrochlorothiazide.
- 1985
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Ingår i: Journal of hypertension. Supplement : official journal of the International Society of Hypertension. - 0952-1178. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to evaluate the potentiating effect of hydrochlorothiazide (HCTZ) 12.5 or 25 mg once daily when added in a placebo-controlled double-blind randomized study of patients with essential hypertension, whose diastolic blood pressure (DBP) was not adequately controlled (DBP > 90 mmHg) following 6 weeks of single-blind treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril, 20 mg once daily. Forty-eight patients started the first period with enalapril after 4 weeks on placebo. In 13 patients DBP fell to < or = 90 mmHg after enalapril for 6 weeks. In this group supine mean arterial pressure (MAP) was reduced by 13% (P < 0.01). In the patients whose DBP was > 90 mmHg after 6 weeks on enalapril (n = 32) the average supine MAP fell by 9% (P < 0.001). After 3 weeks there was no further drop in blood pressure (BP). Addition of HCTZ to the 32 patients with DBP > 90 mmHg caused a significant further drop in supine BP by 13/7 mmHg with 12.5 mg and by 15/7 mmHg with 25 mg. Seven patients discontinued the study, none due to side effects on enalapril alone. Well-being, assessed with a special questionnaire, was significantly better with enalapril as monotherapy compared with previous treatment, but not different from well-being during the placebo periods. It is concluded that 20 mg enalapril once daily lowered BP effectively and was well tolerated. The maximum BP lowering effect was seen within 3 weeks. Addition of HCTZ caused a significant, and clinically relevant, further drop in BP.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 4. |
- Dahlöf, Björn, 1953, et al.
(författare)
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The long-term effect of isradipine in pindolol-treated patients.
- 1987
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Ingår i: Journal of hypertension. Supplement : official journal of the International Society of Hypertension. - 0952-1178. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The long-term efficacy of isradipine, a new dihydropyridine calcium antagonist with marked vascular selectivity, was evaluated in 17 patients with essential hypertension. All had a supine diastolic blood pressure of greater than 95 mmHg with 10 mg pindolol once daily. After a short-term, double-blind, dose-finding, crossover comparison with addition of isradipine or placebo twice daily, they continued on pindolol and their optimal dose of isradipine in a single-blind, long-term follow-up study. Eighteen patients were recruited but one male patient discontinued treatment after 2 weeks due to ankle oedema and will not be accounted for in the overall evaluation. There were 11 males and six females with a mean age of 56 +/- 10 years. In the short-term study on the optimal dose of isradipine (5.1 mg twice daily) blood pressure was lowered by 24/18 mmHg (P less than 0.001). No change in heart rate was seen despite the substantial drop in blood pressure. In the long-term study the patients were seen for a mean follow-up time of 12.5 months (range 4-17 months). After the longest follow-up time mean arterial pressure was 107.0 +/- 7.4 compared with 120.1 +/- 8.2 mmHg after placebo baseline [delta = 13 mmHg (11%), P less than 0.001, n = 17]. The heart rate was unchanged (delta = 0.2 beats/min, 95% confidence limits -3, +3), and so was ankle circumference (delta = 0.12 cm, 95% confidence interval, -1, +1). On the other hand, mean weight was reduced by 2 kg from 90 kg (P less than 0.05, n = 17).(ABSTRACT TRUNCATED AT 250 WORDS)
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| 5. |
- Eggertsen, Robert, 1948, et al.
(författare)
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Acute and long-term hemodynamic effects of carvedilol, a combined beta-adrenoceptor blocking and precapillary vasodilating agent, in hypertensive patients.
- 1987
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 10 Suppl 11
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of these studies was to investigate the hemodynamic effects of carvedilol, a compound with combined properties of nonselective beta-adrenoceptor blockade and precapillary vasodilatation. The acute effects were studied with invasive technique (dye dilution) in 10 patients taking 25 mg orally and noninvasively (forearm plethysmography) in 10 patients taking 25 mg and in 10 patients taking 50 mg orally, all with essential hypertension. Significant reductions of systolic and diastolic blood pressure (p less than 0.05-0.001) were observed in all groups. Total peripheral resistance (TPR) did not change acutely whereas resistance in the forearm was reduced by 16% (p less than 0.05; invasive group). When a comparison with propranolol (80 mg x 2) was made in a randomized double-blind placebo controlled trial in 30 patients, carvedilol acutely reduced blood pressure significantly by 13/6 mg Hg (25 mg) and 17/10 mm Hg (50 mg) in contrast to propranolol. Resistance in the forearm fell significantly with 50 mg carvedilol, whereas propranolol caused a significant rise. After 4 weeks, both compounds had reduced blood pressure significantly. Blood flow was still reduced with propranolol in contrast to the findings with carvedilol. In conclusion, the summary of these studies shows that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment, and it has an attractive hemodynamic profile, in agreement with the hemodynamic findings in essential hypertension.
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| 6. |
- Eggertsen, Robert, 1948, et al.
(författare)
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Additive effect of isradipine in combination with captopril in hypertensive patients.
- 1989
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Ingår i: The American journal of medicine. - : Elsevier BV. - 0002-9343. ; 86:4A, s. 124-6
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Tidskriftsartikel (refereegranskat)abstract
- The effects of combined treatment with the calcium antagonist isradipine and the angiotensin-converting enzyme inhibitor captopril were investigated in a randomized, placebo-controlled parallel-group trial comprising 28 patients with essential hypertension. The average age was 50 years (range, 31 to 65 years). After all patients were given captopril 50 mg twice daily plus placebo for four weeks, they were randomly assigned into groups receiving in addition either placebo or isradipine 1.25 mg twice daily in increasing doses at four-week intervals. During Weeks 20 to 24, the captopril plus placebo group was given hydrochlorothiazide 12.5 mg per day. Blood pressure was measured in the morning, 12 hours after tablet intake. Supine blood pressure was reduced in the captopril plus isradipine group by -8/-6, -14/-9, -16/-8, and -11/-7 mm Hg compared with the placebo group. Changes in diastolic blood pressure were statistically significant at Week 8, whereas changes in systolic blood pressure were statistically significant at Weeks 12, 16, and 20. With the addition of hydrochlorothiazide (Weeks 20 to 24), only supine systolic blood pressure was significantly reduced. One patient was withdrawn from the trial due to a rash. The results indicate that combined treatment with a calcium antagonist and an angiotensin-converting enzyme inhibitor is effective in lowering blood pressure and that the combination is well tolerated during long-term therapy. The combination of captopril and isradipine was more effective than captopril given with a low dose of hydrochlorothiazide.
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| 7. |
- Eggertsen, Robert, 1948, et al.
(författare)
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Hemodynamic effects of combined beta-adrenoceptor blockade and precapillary vasodilatation in hypertension.
- 1985
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Ingår i: Acta medica Scandinavica. Supplementum. - : Wiley. - 0365-463X .- 0001-6101. ; 693, s. 115-20
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Tidskriftsartikel (refereegranskat)abstract
- Carvedilol (BM14190) is a new compound with combined properties of nonselective beta-adrenoceptor blockade, devoid of ISA, and precapillary vasodilatation. Its acute hemodynamic effects were studied with invasive technique (dye-dilution using Cardio-Green) in 10 patients taking 25 mg orally and noninvasive (fore-arm plethysmography) in 10 patients taking 25 mg and in 10 patients taking 50 mg orally, all with essential hypertension. Significant reductions of systolic and diastolic blood pressures (p less than 0.05 - 0.001) were observed in all groups. TPR did not change acutely whereas resistance in the fore-arm was reduced by 16% (p less than 0.05). When a comparison with propranolol (80 mgx2) was made in a randomized, double-blind placebo controlled trial comprising 30 patients with essential hypertension, carvedilol acutely reduced blood pressure significantly 13/6 mm Hg (25 mg) and 17/10 mm Hg (50 mg) in contrast to propranolol. Resistance in the fore-arm (plethysmography) fell significantly with carvedilol 50 mg whereas propranolol caused a significant rise. After 4 weeks both compounds had reduced blood pressure significantly and to the same extent. Blood flow was still reduced with propranolol in contrast to the findings with carvedilol. We conclude that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment. It has an attractive hemodynamic profile.
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| 8. |
- Eggertsen, Robert, 1948, et al.
(författare)
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Vasodilators in hypertension--a review with special emphasis on the combined use of vasodilators and beta-adrenoceptor blockers.
- 1985
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Ingår i: International journal of clinical pharmacology, therapy, and toxicology. - 0174-4879. ; 23:8, s. 411-23
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a review of studies dealing with combined beta-adrenoceptor blockade and vasodilatation in the treatment of hypertension. This therapy can be achieved either through the combined use of conventional beta-adrenoceptor blocking compounds given together with vasodilator drugs or with agents which show multiple action of this kind. From a hemodynamic point of view this therapeutic approach is quite logical since most forms of established hypertension are characterized by increased vascular resistance. It can therefore be concluded that combined beta-adrenoceptor blockade and vasodilation offers a rational and useful treatment of hypertension.
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