Norvasc scientific update |
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Clin Ther. 2003 May;25(5):1469-89.
Volpe M, Junren Z, Maxwell T, Rodriguez A, Gamboa R, Gomez-Fernandez P, Ortega-Gonzalez G, Matadamas N, Rodriguez F, Dass B, Kyle C, Clarysse L, Bryce A, Moreno-Heredia E, Germano G, Gilles L, Smith RD, Sanderson JE; CDSP-944 Study Group.
Universita degli Studi di Roma "La Sapienza", Rome, Italy.
Comparison of the blood pressure-lowering effects and tolerability of Losartan- and Amlodipine-based regimens in patients with isolated systolic hypertension.
BACKGROUND: Elevated systolic blood pressure is a more important risk factor for cardiovascular and renal disease than elevated diastolic blood pressure. Isolated systolic hypertension (ISH) is the predominant form of hypertension in the elderly. Effects of angiotensin II on the vascular wall and endothelium may contribute to development of ISH. OBJECTIVE: The primary objective of this study was to compare the effects on trough sitting systolic blood pressure (SiSBP) of a regimen of losartan, a selective angiotensin II-receptor antagonist, and an amlodipine-based regimen in patients with ISH. METHODS: This multicenter, prospective, randomized, double-blind, parallel-group study consisted of a 4-week placebo phase and an 18-week active-treatment phase. The losartan-based regimen consisted of losartan 50 mg, increased as needed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg at week 6 and to losartan 100 mg/HCTZ 25 mg at week 12 to achieve a target SiSBP <140 mm Hg. the amlodipine-based regimen consisted of amlodipine 5 mg, increased as needed to amlodipine 10 mg at week 6 and to amlodipine 10 mg/HCTZ 25 mg at week 12. The primary efficacy measure was change in trough SiSBP from baseline to week 18. Information on the tolerability of study treatments was collected at each visit, including the investigator's and patient's observations of clinical adverse experiences (CAEs), laboratory adverse experiences, and responses to a symptom questionnaire. RESULTS: Eight hundred fifty-seven patients (65.6% female) were randomized to treatment, 432 in the losartan group and 425 in the amlodipine group. Their mean age was 67.6 years, and they had a mean duration of hypertension of 6.7 years at baseline. The losartan and amlodipine groups (intent-to-treat population) had baseline mean SiSBP values of 171.2 and 171.9 mm Hg, respectively. At week 18 (the primary end point), the mean change from baseline in SiSBP was -27.4 mm Hg for 426 patients who received losartan and -28.1 mm Hg for 419 patients who received amlodipine (estimated least-square mean difference, 0.3 mm Hg; 95% CI, -1.4 to 2.0), indicating that losartan's effect on systolic blood pressure was noninferior to that of amlodipine. The proportion of patients who responded (SiSBP <140 mm Hg or a > or =20-mm Hg decrease in SiSBP from baseline) was comparable between groups (73.9% losartan, 75.4% amlodipine). The incidence of CAEs and drug-related CAEs was significantly greater in the amlodipine group (amlodipine, 79.8% and 43.8%, respectively; losartan, 67.8% and 25.5%; P < or = 0.001). In addition, more patients in the amlodipine group discontinued therapy due to a drug-related CAE compared with patients in the losartan group (12.9% vs 4.4%, respectively; P < or = 0.001). Lower-extremity edema was the most common drug-related CAE in the amlodipine group (24.0% amlodipine, 2.5% losartan; P < or = 0.001); dizziness was the most common drug-related CAE in the losartan group (6.0% losartan, 4.0% amlodipine). CONCLUSIONS: In these patients with ISH, losartan and amlodipine produced comparable clinically relevant reductions in SiSBP; however, losartan was better tolerated, as evidenced by fewer CAEs and discontinuations compared with amlodipine. Losartan may be considered for the initial treatment of ISH.
Adv Perit Dial. 2003;19:10-4.
Ishida Y, Tomori K, Nakamoto H, Imai H, Suzuki H.
Department of Nephrology, Saitama Medical School, Saitama, Japan.
Effects of antihypertensive drugs on peritoneal vessels in hypertensive dogs with mild renal insufficiency.
The transport capacity of any membrane depends on its surface area and permeability. In addition, peritoneal capillaries are probably barriers to solute transport. Although no decisive use of antihypertensive drugs has been reported in continuous ambulatory peritoneal dialysis (CAPD) patients with hypertension, those drugs are known to have various effects on vessels. In the present study, we used a charge-coupled-device (CCD) camera in renovascular hypertensive dogs with mild renal insufficiency to investigate the effects of various antihypertensive drugs on the peritoneal capillaries. Renovascular hypertension was induced in the dogs by placing silver clips on both renal arteries to create 90% occlusion. After confirmation of elevation of blood pressure (usually 20 days after the operation), each dog's abdomen was opened while the animal was under general anesthesia. Using a CCD camera, the diameters of the small arteries of the peritoneum were measured after 3 days' oral administration of a placebo (n = 5); or of 8 mg CS866, a selective angiotensin II type 1 receptor blocker (n = 5); or of 10 mg benazepril, an angiotensin-converting enzyme inhibitor (n = 5); or of 10 mg amlodipine, a calcium antagonist (n = 5). In dogs receiving CS866, blood pressure decreased to 128 +/- 6 mmHg from 160 +/- 6 mmHg (p < 0.01). A similar decrease in blood pressure was observed with the use of the other drugs. The diameter of the small vessels increased by 28% +/- 6% in dogs receiving CS866 and by 24% +/- 5% in dogs receiving benazepril, as compared with 3% +/- 3% in dogs receiving the calcium antagonist. These data clearly demonstrate that blockade of the renin-angiotensin system produces an increase in solute clearance in hypertensive dogs with mild renal insufficiency and that such blockade may be applicable as therapy for hypertensive patients on CAPD.
Expert Opin Pharmacother. 2004 Feb;5(2):459-68.
Jukema JW, van der Hoorn JW.
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Amlodipine and atorvastatin in atherosclerosis: a review of the potential of combination therapy.
Hypertension and hyperlipidaemia are major risk factors for the development of atherosclerosis. Calcium channel blockers (CCBs) have been used for decades and have established antihypertensive effects. Statins have been extensively used because of their potent lipid lowering properties. Amongst other factors, inflammation and oxidation are involved in enhanced progression of atherosclerosis and new lesion development. Therefore, research has been initiated focusing on the antioxidant and anti-inflammatory properties of CCBs and statins, beyond their primary effect, in order to evaluate the possible additive effects of combined treatment of CCBs with statins as antiatherosclerotic therapy. Clinical studies (e.g., the International Nifedipine Trial on Antiatherosclerotic Therapy [INTACT]) have demonstrated that the antiatherosclerotic action of CCBs is limited to the attenuation of the first stage of atherosclerogenesis (fatty streak formation or new lesion growth). The lesions that pre-existed at the start of CCB therapy did not demonstrate progression or regression on angiography. However, because the mechanisms of action of lipid-lowering drugs and CCBs, and their role in preventing the progression of atherosclerosis differ, it is conceivable to conclude that these two classes may have an additive or synergic effect, not only on new lesion formation but also on inhibiting the progression of established coronary atherosclerosis. Indeed, this combined effect of lipid-lowering therapy and CCBs on human coronary atherosclerosis has been reported in the Regression Growth Evaluation Statin Study (REGRESS) trial. This beneficial effect of combining CCBs with statins has now been replicated in transgenic atherosclerotic mice, where the combination of amlodipine and atorvastatin produced an additional 60% reduction of atherosclerosis compared with that observed with the statin alone. Serum markers of atherosclerosis and vascular integrity also improved most in the combination group. Synergistic effects of the combination of atorvastatin and amlodipine on acute nitric oxide release/endothelial function, and additive effects of the combination of amlodipine and atorvastatin in the improvement of arterial compliance in hypertensive hyperlipidaemic patients has been demonstrated. Collectively, these studies support the clinical antiatherosclerotic advantages of combination of CCBs and statins and in particular, of atorvastatin with amlodipine beyond their established antihyperlipidaemic and antihypertensive modes of action.
Ann Pharmacother. 2005 Feb 22; [Epub ahead of print]
Sener D, Halil M, Yavuz BB, Cankurtaran M, Ariogul S.
Medical Faculty, Department of Internal Medicine, Hacettepe University, Ankara, Turkey.
Anasarca Edema with Amlodipine Treatment (April).
OBJECTIVE: To report a case of anasarca edema associated with amlodipine use. CASE SUMMARY: A 77-year-old woman with essential hypertension who had not been treated with any other drug was prescribed amlodipine 10 mg/day to control her blood pressure. She developed anasarca edema soon after amlodipine treatment was initiated. Laboratory test results for possible etiologies were negative. Discontinuation of amlodipine resulted in dramatic improvement. DISCUSSION: To our knowledge, as of February 3, 2005, there have been no other reports of amlodipine-related anasarca edema in the English literature, and only one case was described in the Japanese literature. Pretibial edema is the most common adverse effect of amlodipine. Periocular and perioral edema have occurred less frequently, but anasarca edema has not emerged as a problem. An objective causality assessment revealed amlodipine to be a probable cause of anasarca edema. CONCLUSIONS: In rare instances, amlodipine may cause generalized edema, which will resolve upon discontinuation of the drug.
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Drug category:Hypotensive agents
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