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Combination therapy with an Xa inhibitor and antihypertensive agent improved anticoagulant activity in patients with nonvalvular atrial fibrillation: the hypertension and atrial fibrillation treated by rivaroxaban for the morning and night with sYnergy with calcium antagonists (HARMONY) study.
Kabutoya, T, Ohmori, T, Fujiwara, T, Kario, K
Clinical and experimental hypertension (New York, N.Y. : 1993). 2020;(4):365-370
Abstract
Background: Anticoagulant activity and blood pressure increase in the morning. The aim of this study was to evaluate changes of anticoagulant activity, blood pressure and target organ damage in patients with nonvalvular atrial fibrillation (AF) given combination treatment with Xa inhibitor and antihypertensive agent.Methods: We enrolled 72 patients with nonvalvular AF. Rivaroxaban (10-15 mg) was continuously administered once daily over 8 weeks (study period I). For subjects (n = 50) who exhibited uncontrolled morning hypertension (home systolic blood pressure [SBP]≥125 mmHg) at the end of study period I (at 8 weeks), nifedipine CR (20-40 mg) was added at bedtime, and rivaroxaban administration was continued an additional 8 weeks. We assessed prothrombin fragment 1 + 2 (optimal range: 69-229 pmol/L) and D-dimer (negative D-dimer measurement: <1.0 μg/mL).Results: The percentage of patients with optimal-range prothrombin fragment 1 + 2 was significantly increased at 4 weeks compared to baseline (70.8% vs. 86.1%, p = .033). In period II, office and home morning SBP were reduced at 12 compared to 8 weeks (office SBP: 135.2 ± 15.7 vs. 125.6 ± 18.4mmHg, p < .001; home morning SBP: 133.5 ± 10.5 vs. 119.9 ± 12.1mmHg, p<.001).The percentage of patients with negative D-dimer was increased at 8 weeks compared to baseline (92% vs. 100%, p = .044), and remained at 100% at 16 weeks.Conclusions: Xa inhibitor therapy improved anticoagulant activity, and additional antihypertensive therapy maintained the anticoagulant activity in patients with nonvalvular AF.
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Endothelin Receptor Antagonism Improves Lipid Profiles and Lowers PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) in Patients With Chronic Kidney Disease.
Farrah, TE, Anand, A, Gallacher, PJ, Kimmitt, R, Carter, E, Dear, JW, Mills, NL, Webb, DJ, Dhaun, N
Hypertension (Dallas, Tex. : 1979). 2019;(2):323-330
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Abstract
Dyslipidemia is common in chronic kidney disease (CKD). Despite statins, many patients fail to adequately lower lipids and remain at increased risk of cardiovascular disease. Selective ETA (endothelin-A) receptor antagonists reduce cardiovascular disease risk factors. Preclinical data suggest that ETA antagonism has beneficial effects on circulating lipids. We assessed the effects of selective ETA antagonism on circulating lipids and PCSK9 (proprotein convertase subtilisin/kexin type 9) in CKD. This was a secondary analysis of a fully randomized, double-blind, 3-phase crossover study. Twenty-seven subjects with predialysis CKD on optimal cardio- and renoprotective treatment were randomly assigned to receive 6 weeks dosing with placebo, the selective ETA receptor antagonist, sitaxentan, or long-acting nifedipine. We measured circulating lipids and PCSK9 at baseline and then after 3 and 6 weeks. Baseline lipids and PCSK9 did not differ before each study phase. Whereas placebo and nifedipine had no effect on lipids, 6 weeks of ETA antagonism significantly reduced total (-11±1%) and low-density lipoprotein-associated (-20±3%) cholesterol, lipoprotein (a) (-16±2%) and triglycerides (-20±4%); high-density lipoprotein-associated cholesterol increased (+14±2%), P<0.05 versus baseline for all. Additionally, ETA receptor antagonism, but neither placebo nor nifedipine, reduced circulating PCSK9 (-19±2%; P<0.001 versus baseline; P<0.05 versus nifedipine and placebo). These effects were independent of statin use and changes in blood pressure or proteinuria. Selective ETA antagonism improves lipid profiles in optimally-managed patients with CKD, effects that may occur through a reduction in circulating PCSK9. ETA receptor antagonism offers a potentially novel strategy to reduce cardiovascular disease risk in CKD. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00810732.
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Nifedipine Treatment for Hypertension is Associated with Enhanced Lipolytic Activity and Accelerated Clearance of Postprandial Lipemia.
Grosskopf, I, Shaish, A, Charach, G, Harats, D, Kamari, Y
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2016;(4):257-62
Abstract
Hypertension, advanced age, postprandial hyperlipidemia, and insulin resistance are major risk factors for atherosclerosis. The calcium channel blocker nifedipine is reported to ameliorate insulin resistance possibly by activating PPARγ. This is expected to become accentuated in elderly individuals due to age-related insulin resistance. Insulin resistance modulates lipoprotein metabolism. Therefore, we reasoned that nifedipne offers the potential for improving postprandial lipemia in association with increasing age. We studied the effect of nifedipine on fasting lipids, postprandial lipemia, insulin sensitivity, and plasma lipolytic activity in 24 and 15 hypertensive subjects aged 70-75 years and 40-45 years, respectively. As expected, nifedipine significantly lowered systolic and diastolic blood pressure. Nifedipine decreased fasting triglyceride level (23%) and increased HDL-C (15%) in the elderly group. At baseline, postprandial triglyceride levels were remarkably elevated in elderly compared to younger patients (1 288±798 vs. 501±260 mg·dl(-1)·h, p<0.05), as was retinyl palmitate (surrogate marker for intestinally-derived cholesterol) in the chylomicrons (45.0±26.5 vs. 23.4±10.6 mg·l(-1)·h, p<0.05) and chylomicron remnant (15.2±5.4 vs. 11.7±4.7 mg·l(-1)·h, p<0.05) fractions. Importantly, while the level of chylomicron remnants in the group of younger subjects remained unchanged after treatment, nifedipine was associated with a significantly decreased chylomicron remnants retinyl palmitate in the elderly group, which dropped to levels, observed in younger subjects. This was accompanied by enhanced insulin sensitivity and augmented plasma lipolytic activity. The present work suggests that nifedipine has favorable metabolic effects that are beyond the known enhancement of insulin sensitivity. The improvement in postprandial lipidemia by nifedipine may add to its anti-atherogenic effects in hypertensive patients.
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Restless legs syndrome in hemodialysis patients: association with calcium antagonists. A preliminary report.
Telarović, S, Relja, M, Trkulja, V
European neurology. 2007;(3):166-9
Abstract
Uremia-related restless legs syndrome (RLS) is a known form of secondary RLS. This cross-sectional survey included patients (n = 82) on stable hemodialysis (HD; >3 months, Kt/V >1.2) who were iron-replete, free of neurodegenerative or psychiatric disorders, severe polyneuropathy and radiculopathy, not exposed to antipsychotics/antidepressants, and not severely anemic. Forty-nine (60%) were RLS 'positive', and 25 (31%) had severe/very severe symptoms (International Restless Legs Syndrome Study Group criteria). None had been diagnosed previously. In a multivariate analysis, the prevalence of RLS was higher in diabetic patients [vs. nondiabetics; prevalence ratio (PR) 2.32, 95% CI 1.50-3.60, p < 0.001] and those exposed to Ca2+ antagonists (vs. nonexposed; PR 2.02, CI 1.47-2.76, p < 0.001), and also increased with dialysis duration (PR 1.05, 95% CI 1.02-1.09, p < 0.001). Association of Ca2+ antagonists and RLS in uremic patients has not been reported previously and deserves further research.
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[Rational approach to selection of antihypertensive therapy in persons with metabolic syndrome: efficacy of monotherapy with spirapril and its combination with retard form of nifedipine].
Mamedov, MN, Kiseleva, NV
Kardiologiia. 2006;(9):26-30
Abstract
AIM: Achievement of target blood pressure (BP) levels in subjects with metabolic syndrome (MS) by the method of stepwise antihypertensive therapy and assessment of metabolic effects of combination of spirapril and nifedipine retard. MATERIAL AND METHODS Patients (n=20, 12 women, 8 men, mean age 54+/-3 years) with MS were first given spirapril (6 mg/day). Nifedipine retard (40 mg/day) was added if target BP was not achieved after 4 weeks. Study duration was 12 weeks. The following parameters were measured at baseline and at study end: heart rate, blood pressure, body mass, waist circumference, parameters of lipid spectrum, content of insulin including index HOMA IR, blood glucose (fasting and during oral glucose tolerance test). RESULTS Target BP levels were achieved in 18 patients (90%)--in 11 with moexipril monotherapy, in 9--after addition of nifedipine. Lowering of systolic and diastolic BP from baseline was 11 and 14%, respectively. After 3 months of combination antihypertensive therapy triglyceride levels decreased by 28% while high density lipoprotein cholesterol (CH) increased 6%. Total, low density lipoprotein CH and coefficient of atherogenecity did not change as well as fasting blood glucose after fast and oral glucose tolerance test. Concentration of fasting immunoreactive insulin significantly decreased by 34% entailing 35% decrease of insulin resistance. Therapy was well tolerated, side effects were transitory and did not cause withdrawal of treatment. CONCLUSION In patients with MS and mild hypertension monotherapy with spirapril and combination of spirapril with nifedipine retard caused lowering of BP to target level in 55 and 90%, respectively. Combination of spirapril and nifedipine retard exerts positive metabolic action.
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Control of edema in hypertensive subjects treated with calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitors with Pycnogenol.
Belcaro, G, Cesarone, MR, Ricci, A, Cornelli, U, Rodhewald, P, Ledda, A, Di Renzo, A, Stuard, S, Cacchio, M, Vinciguerra, G, et al
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2006;(4):440-4
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Abstract
The presence of edema in different phases and stages of essential hypertension may be due to antihypertensive treatment. Some drugs may cause edema by inducing vasodilatation, increasing the capillary exchange surface and capillary filtration. Pycnogenol has an important anti-edema effect in diabetic microangiopathy and chronic venous insufficiency. This 8-week study evaluated capillary filtration in 2 comparable treatment groups with hypertension treated with a calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitor to define its efficacy in preventing edema caused by antihypertensives. A significant decrease in filtration was observed in the Pycnogenol groups. Pycnogenol controls this type of edema, it helps to prevent and limit long-term damage in the microcirculation in hypertensive patients, and allows the dose of anti-hypertensive drugs to be reduced in most patients.
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Comparison between nifedipine and carvedilol in the treatment of de novo arterial hypertension after liver transplantation: preliminary results of a controlled clinical trial.
Galioto, A, Angeli, P, Guarda, S, Burra, P, Zanus, G, Fasolato, S, Fagiuoli, S, Sticca, A, Semplicini, A, Sartori, M, et al
Transplantation proceedings. 2005;(2):1245-7
Abstract
There is no controlled clinical trial on the treatment of de novo arterial hypertension after liver transplantation (LT) a common complication using calcineurin inhibitors (CNI) for immunosuppressive therapy. The aim of this study was to compare the efficacy and safety of nifedipine, a calcium channel blocker, and carvedilol, an alpha1- and beta-blocker. The study included 50 patients who developed arterial hypertension after LT. The data on the first 30 patients who have completed 12-month follow-up are reported herein. Eighteen patients received nifedipine, and 12 patients received carvedilol. Patients were evaluated monthly at the outpatient clinic for 1 year. If patients developed severe adverse effects to nifedipine, they were switched to carvedilol and vice versa (therapy failure). The two groups were similar for clinical features, indications for LT, immunosuppressive therapy, and baseline blood pressures. A failure of treatment was observed in 9 of 18 patients treated with nifedipine (50.0%) and one of 12 patients treated with carvedilol (8%, P < .025). Nifedipine was effective in 4 of 18 patients, carvedilol, in 4 of 12 patients (22.21% vs 33.3%, P = NS). Two of the nine nonresponders to nifedipine responded to carvedilol. The efficacy of monotherapy was observed in 11 of 40 randomized patients (27.5%). Carvedilol monotherapy is as effective as nifedipine but far better tolerated.
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Randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in medical expulsive therapy for distal ureteral calculi.
Dellabella, M, Milanese, G, Muzzonigro, G
The Journal of urology. 2005;(1):167-72
Abstract
PURPOSE Recent studies show the interesting efficacy of different drug combinations for the spontaneous expulsion of distal ureteral stones. We performed a randomized, prospective study to assess and compare the efficacy of 3 drugs as medical expulsive therapy for distal ureteral calculi. MATERIALS AND METHODS A total of 210 symptomatic patients with distal ureteral calculi greater than 4 mm were randomly allocated to home treatment with phloroglucinol, tamsulosin or nifedipine (groups 1 to 3, respectively). Each group was given a corticosteroid drug and antibiotic prophylaxis with an injectable nonsteroidal anti-inflammatory drug was also used on demand. The primary end point was the expulsion rate and the secondary end points were expulsion time, analgesic use, need for hospitalization and endoscopic treatment as well as the number of workdays lost, quality of life and drug side effects RESULTS The expulsion rate was significantly higher in group 2 (97.1%) than in groups 1 (64.3%, p <0.0001) or 3 (77.1%, p <0.0001). Group 2 significantly achieved stone passage in a shorter time than the other 2 groups and showed a significantly decreased number of hospitalizations as well as a better decrease in endoscopic procedures performed to remove the stone. The control of renal colic pain was significantly superior in group 2 compared with the other groups, resulting in fewer workdays lost. Group 3 showed lower analgesic use and decreased workdays lost compared with group 1. No difference in side effects was observed among the groups. CONCLUSIONS Medical expulsive therapy should be considered for distal ureterolithiasis without complications before ureteroscopy or extracorporeal lithotripsy. The use of tamsulosin in this treatment regimen produced stone expulsion in almost all cases in a short time, allowing complete home patient treatment.
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Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with symptomatic stable angina and hypertension: the ACTION trial.
Lubsen, J, Wagener, G, Kirwan, BA, de Brouwer, S, Poole-Wilson, PA, ,
Journal of hypertension. 2005;(3):641-8
Abstract
OBJECTIVE To examine the effects of nifedipine GITS on clinical outcome in patients with concurrent stable angina and hypertension. METHODS Data from the double-blind placebo-controlled ACTION trial was stratified for hypertension (blood pressure > or = 140/90 mmHg), at baseline. RESULTS A total of 52% of 7665 ACTION patients were hypertensive. Some 80% were on a beta blocker; hypertensives were more often treated with other blood pressure-lowering drugs. Mean baseline blood pressure was 122/74 mmHg among normotensives and 151/85 mmHg among hypertensives. Follow-up blood pressures were reduced by nifedipine (P < 0.001) on the average by 3.9/2.4 and 6.6/3.5 mmHg among normotensives and hypertensives, respectively. Nifedipine GITS significantly (P < 0.05) reduced the combined incidence of all-cause mortality, myocardial infarction, refractory angina, heart failure, stroke and peripheral revascularization by 13% in hypertensives only. Nifedipine significantly reduced the incidence of any stroke or transient ischemic attack by almost 30% in both subgroups and the need for coronary angiography by 21% in normotensives and 16% in hypertensives. Among hypertensives, the incidence of new overt heart failure was significantly reduced by 38% and of debilitating stroke by 33%. Among normotensives, the need for coronary bypass grafting was significantly reduced by 32%. Nifedipine did not affect all-cause death, cardiovascular death and myocardial infarction in either normo- or hypertensives, but increased the need for peripheral revascularization. CONCLUSION The salutary effects of the addition of nifedipine GITS to the basic regimen of patients with concurrent stable symptomatic coronary artery disease and hypertension emphasize the need for blood pressure control.
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Single- or double-blind treatment With Balsamodendron mukul and nifedipine in hypertensive patients.
Panneerselvam, J, Sambandam, G, Nalini, N
Journal of clinical hypertension (Greenwich, Conn.). 2005;(6):340-5
Abstract
This study assessed and compared the effects of Balsamodendron mukul (an extract of the gum of a small tree) and nifedipine (a calcium-channel-blocking reference drug) on blood pressure, lipids, lipoproteins, and phospholipids in randomly selected patients with essential hypertension. Fifty-seven newly diagnosed hypertensive patients were randomly divided into three groups. They received either single-blind B. mukul (1.5 g/d) or single-blind nifedipine (10 mg/d) double-blind therapy with nifedipine (10 mg/d) and B. mukul (1.5 g/d) for 6 weeks. These groups were compared with control subjects. On treatment with B. mukul, levels of systolic blood pressure, diastolic blood pressure, plasma total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, free fatty acids, and phospholipid levels were significantly reduced, and high-density lipoprotein cholesterol levels were significantly elevated, as compared with untreated hypertensive patients. Combined therapy with B. mukul and nifedipine was more beneficial than the treatment with B. mukul alone. Our study suggests that B. mukul may be an effective antihypertensive and hypolipidemic agent.