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Long-term evaluation of cilazapril in severe hypertension. Assessment of left ventricular and renal function.

Sanchez RA, Traballi CA, Marco EJ, Cianciulli T, Giannone CA, Ramirez AJ.

Instituto de Cardiologia, Academia Nacional de Medicina, Buenos Aires, Argentina.

The effect of cilazapril as monotherapy or in combination with hydrochlorothiazide was assessed in 30 severely hypertensive patients, 23 men and seven women, aged 38 to 68 years, with sitting diastolic blood pressure of more than 115 mmHg. Fifteen patients had left ventricular hypertrophy documented by two-dimensional echo-cardiography. Sitting systolic blood pressure was reduced from 175.8 +/- 2.0 to 143.3 +/- 3.0 mmHg within 25 days of therapy (p less than 0.0001); sitting diastolic blood pressure decreased in the same period from 117.0 +/- 1.0 to 87.8 +/- 2.0 mmHg (p less than 0.0001), whereas heart rate remained unchanged. In 19 patients treated for an average of 48 weeks the therapeutic response was maintained during the long-term period. The mean effective dose was cilazapril 10 mg plus hydrochlorothiazide 12.5 to 25 mg in 90 percent of the patients. Left ventricular mass decreased from 357 +/- 17 to 314 +/- 22 g (nine patients; p less than 0.005) and a correlation (Spearman r = 0.57, p less than 0.01) was found between left ventricular mass and sitting systolic blood pressure before and during treatment. Deceleration half time of peak early diastolic inflow velocity decreased significantly from 128 +/- 9 to 108 +/- 7 msec (p less than 0.05). Glomerular filtration rate and renal blood flow remained within normal limits, whereas renal vascular resistance decreased from 0.16 +/- 0.0 to 0.10 +/- 0.0 resistance units (10 patients; p less than 0.01). Cilazapril in combination with hydrochlorothiazide was effective in the treatment of severe hypertension. Left ventricular hypertrophy regression influenced favorably left ventricular diastolic function in some patients, whereas renal hemodynamics were generally not affected by the therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2532462&dopt=Abstract hydrochlorothiazide Microzide



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The antihypertensive response to lisinopril: the effect of age in a predominantly black population.

Cummings DM, Amadio P Jr, Taylor EJ Jr, Balaban DJ, Rocci ML Jr, Abrams WB, Feinberg J, Vlasses PH.

Department of Family Medicine, Jefferson Medical College of Thomas Jefferson University.

After a 2-4 week no-treatment period, 24 patients (12 young, age 29-45 yr.; 12 elderly, age 65-81 yr.; 20 black, 4 white) with an untreated sitting diastolic blood pressure between 91-120 mm Hg received the nonsulfhydryl angiotensin converting enzyme inhibitor, lisinopril for three weeks in a singleblind, parallel group comparison. Patients who did not achieve goal blood pressure with the initial low-dose (10 mg/day) were treated with a high-dose regimen (40 mg/day) for three weeks. In those who remained incompletely responsive, hydrochlorothiazide 25 mg/day was added for four weeks in an attempt to normalize blood pressure (less than or equal to 90 mm Hg). Low-dose lisinopril monotherapy produced comparable reductions in the mean systolic and diastolic blood pressures (approximately -15/-8 mm Hg in both younger and older patients). Increasing the dose produced a slightly greater fall in mean blood pressures which normalized the blood pressure in five of six elderly patients unresponsive to the lower dose; addition of hydrochlorothiazide normalized three of the five remaining subjects from both groups who were unresponsive to high dose lisinopril. Lisinopril administration resulted in a rise in plasma renin activity and a fall in plasma aldosterone concentrations which were similar in both groups and which returned over time toward the baseline. The drug was well tolerated, producing one episode of symptomatic hypotension following the addition of hydrochlorothiazide to lisinopril monotherapy. Lisinopril alone or in combination with hydrochlorothiazide produces favorable antihypertensive effects in both younger and older predominantly black, low-renin patients with essential hypertension.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2540224&dopt=Abstract hydrochlorothiazide Microzide



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Advances in antihypertensive combination therapy: benefits of low-dose thiazide diuretics in conjunction with omapatrilat, a vasopeptidase inhibitor.

Ferdinand KC.

Department of Clinical Pharmacology, Xavier University College of Pharmacy, New Orleans, LA, USA.

The preferred initial agents for the treatment of high blood pressure are low-dose thiazide diuretics, beta blockers, calcium antagonists, and angiotensin-converting enzyme (ACE) inhibitors. In high-risk patients, including those with diabetes, renal insufficiency, left ventricular dysfunction, and atherosclerosis, ACE inhibitors may have specific benefit in reducing cardiovascular morbidity and mortality. Omapatrilat, the prototypical vasopeptidase inhibitor, inhibits not only ACE but also neutral endopeptidase. Like conventional ACE inhibitors, omapatrilat causes extracellular volume reduction and vasodilatation; moreover, it increases levels of atrial and brain natriuretic peptides and bradykinin. Effective blood pressure control, especially in the high-risk patient, usually necessitates combination therapy. A recent study randomized 274 subjects with mild to severe hypertension (stages 1-3 diastolic blood pressure elevation) and confirmed the benefits of omapatrilat combined with hydrochlorothiazide in patients not controlled on hydrochlorothiazide alone. The frequencies of adverse events, serious adverse events, and discontinuation attributed to adverse events were similar for omapatrilat and placebo. Furthermore, there were no clinically significant changes in serum creatinine, potassium, or other laboratory parameters. Adding omapatrilat to the background of hydrochlorothiazide treatment produced statistically significant additional reductions in trough diastolic and systolic blood pressures at weeks 4 and 8.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11588409&dopt=Abstract hydrochlorothiazide Microzide



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[Patterns of antihypertensive agents use in 11,947 Colombian patients]

[Article in Spanish]

Isaza CA, Osorio FJ, Mesa G, Moncada JC.

Facultad de Ciencias de la Salud, Universidad Tecnologica de Pereira, Pereira, Colombia.

In Colombian populations older than 15 years, 12.6% suffer from hypertensive disease. Pharmacological therapies for hypertension and associated diseases were compared for 11,947 adult hypertensive patients of both sexes. All had been in treatment for more than 3 months (November/01-January/02), and were distributed among six Colombian cities. The data were retrieved from medication consumption registers that were maintained by the institutions that distribute medications to patients selected for the study. The average age of patients was 55.8 +/- 13.8, and 67.7% were women. Men were older (p < 0.05) and consumed other drugs more than women (67.7% vs. 62.4%, p < 0.05); 53.2% of patients received only one drug and 46.8% received between 2 to 5 drugs for hypertension disease. Medications most commonly prescribed were hydrchlorothiazide (31.8%), captopril (27.9%), verapamil (27.6%), enalapril (25%), metoprolol (15.1%) and propranolol (14.9%). The most common combinations were hydrochlorothiazide + ACE inhibitors (n = 2,001), hydrochlorothiazide + calcium channel antagonists (n = 1,367), verapamil + ACE inhibitors (n = 1,153) and hydrochlorothiazide + beta blocker (n = 1,021). Other prescribed medications included ASA as antiplatelet (38.2% of patients), nonsteroidal anti-inflammatory drugs (NSAID, 16.2%), lipid-lowering drugs (11.8%), hypoglycemic agents (10.9%) and antiulcerous drugs (9.6%). Some agents are probably underemployed (ACE inhibitors, ASA) and others overused (antiulcerous). Potentially dangerous pharmacological interactions were discovered in 410 cases (3.43%). Significant differences occurred in physicians' formulations among the six cities, but rational prescription patterns prevailed. Newly designed educational strategies are recommended to prevent administration of potential harmful combinations. Further exploration of clinical results in these formulations is indicated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12596445&dopt=Abstract hydrochlorothiazide Microzide



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Interference of different ACE-inhibitors with the diuretic action of furosemide and hydrochlorothiazide.

Toussaint C, Masselink A, Gentges A, Wambach G, Bonner G.

Klinik II, Universitat zu Koln, Klinikum Merheim.

In healthy volunteers the acute effect of furosemide (40 mg i.v.) and hydrochlorothiazide (100 mg p.o.) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated. Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly probably due to a diminished (about 50%) proximal-tubular secretion of furosemide. Captopril did not alter significantly the furosemide induced changes in urinary kallikrein and kinin excretion. After captopril there was a clear dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. Other ACE-inhibitors like ramipril (5 mg) or enalapril (20 mg) did not influence the stimulatory effects of furosemide on diuresis or kallikrein-kinin excretion. Ramipril at a dose of 10 mg, however, enhanced the initial diuretic effect of furosemide by increased furosemide secretion and increased relative sodium excretion. Hydrochlorothiazide induced a prolonged diuresis which was not changed by either captopril or ramipril. Urinary kallikrein excretion was not stimulated by hydrochlorothiazide. Our results show an important drug interference between captopril and furosemide, which is independent of ACE-inhibition and probably only due to an interference in proximal-tubular secretion of both drugs. Between captopril and hydrochlorothiazide no such interaction could be observed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2586018&dopt=Abstract hydrochlorothiazide Microzide