Biomedical subjects

F Zannad

Publications and source records attributed to F Zannad.

At least 91 records · Page 5Linked to original sources

PubMed1996

Assessment of drug efficacy using home self-blood pressure measurement: the SMART study. Self Measurement for the Assessment of the Response to Trandolapril.

UNLABELLED: The SMART study (Self Measurement for the Assessment of the Response to Trandolapril) was a large scale trial conducted by general practitioners in order to assess the informative value of home self-measured blood pressure (BP) for the evaluation of therapeutic intervention. After a 2-week wash-out period, patients with office diastolic blood pressure (DBP) between 95 and 120 mm Hg received trandolapril, 2 mg once daily for 4 weeks. Four days of self-recorded BP were performed both at the end of the wash-out period and at the end of the treatment period with an automatic printerequipped device using the oscillometric method (A&D UA 751). Every day, a series of three consecutive measurements was planned in the morning before drug intake and repeated in the evening. A total of 1710 patients (946 men, 764 women) aged 56 +/- 11 entered the study. In the 816 patients who correctly performed self-measured blood pressure (SMBP) during both periods and followed the protocol schedule, office BP (SBP/DBP) decreased from 166.4 +/- 15/101.4 +/- 6 mm Hg to 144.7 +/- 14/86.1 +/- 8 mm Hg while SMBP decreased from 153 +/- 18/94 +/- 10 mm Hg to 139 +/- 16/85 +/- 10 mm Hg. A weak correlation was found between the two methods with regard to systolic (r = 0.47, P < 0.0001) and diastolic (r = 0.36, P < 0.0001) BP lowering. Individual response to therapy varied between the two methods: 633 patients (77.6%) exhibited at least a 10 mm Hg office DBP decrease while 493 (60.4%) presented at least a 6 mm Hg self measured DBP decrease in the evening; 65% of patients were considered as responders with both methods. The 24-h therapeutic coverage was assessed by the morning to evening BP decrease ratio (M/E ratio) which represents the ratio of the trough effect to the 12-h post dosing efficacy. Both population and individual M/E ratios ranged between 73% and 86% thus confirming the long duration of action of trandolapril. IN CONCLUSION: (1) discrepancies between office and self-measured BP evaluation of therapeutic response have been pointed out: agreement between the two methods is obtained in only 65% of patients, mainly due to intra-individual BP variability and recording conditions; and (2) self-measured BP could be a potential tool to explore the 24-h therapeutic coverage.

Adolescent↗

PubMed1995

Clinical pharmacology of nisoldipine coat core.

Nisoldipine is a second-generation dihydropyridine calcium antagonist structurally related to nifedipine and used in the treatment of stable angina and arterial hypertension. It is also under investigation for the treatment of left ventricular dysfunction. It was first developed as an immediate release tablet, but this formulation was not considered optimal for once-daily administration because of the variable results obtained at peak and trough in clinical studies. Consequently, nisoldipine coat core (CC) was developed with the aim of optimizing the drug's time--effect profile over the 24-hour dosing interval. The in vitro release pattern classifies this tablet as an "extended release" formulation according to European Community guidelines. The present article outlines the pharmacokinetic and pharmacodynamic profiles of nisoldipine CC, as obtained from recent clinical studies.

Coronary Circulation↗

PubMed1995

Duration of action of angiotensin converting enzyme inhibitors.

Duration of action of an angiotensin converting enzyme (ACE) inhibitor is not solely related to its individual elimination half-life. It is also determined by its ACE inhibiting potency and affinity for ACE. Its degree of lipophilicity is also an important factor in determining tissue penetration. Any attempt to calculate the duration of action, and, consequently, the interdosing interval, of an ACE inhibitor should take into account and integrate all these variables. The measurement (or the calculation) of each of these variables is not in itself an easy task and is very much prone to error. Given the failure of pharmacokinetic and pharmacodynamic studies to provide an adequate and simple method capable of predicting reliably the time-effect relationship of ACE inhibitors, it is obvious that the pragmatic way to determine this time-effect profile is to monitor blood pressure changes during the clinical use of a given ACE inhibitor. Because very little information is available for many ACE inhibitors concerning their trough/peak ratio, we have recently reviewed all the published studies assessing the antihypertensive efficacy of commercially available ACE inhibitors with ambulatory blood pressure monitoring. Our literature analysis suggests that not all once daily ACE inhibitors comply with the Food and Drug Administration requirement of a trough/peak ratio higher than 50%. However, current evidence suggests that the definition of this ratio is dependent upon the methodology employed for its determination. The only validated analytical approach that is based on blood pressure measurements in a few confined patients, during phase II dose-finding studies. Fuller information may be sought with alternative evaluative approaches based on ambulatory BP measurements in large numbers of patients and in more pragmatic daily life conditions. Although this remains to be demonstrated, long acting ACE inhibitors may provide additional benefits over the shorter acting ones by producing an optimal 24 h and longer therapeutic coverage, with fewer peak-effect related side effects and better control of blood pressure during critical nighttime and early morning hours.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Aldosterone and heart failure.

In untreated congestive heart failure, aldosterone plasma concentrations are elevated in proportion to the severity of the disease and are further increased by the use of diuretic treatment. Angiotensin II, plasma potassium concentration, and corticotropin are the major stimulators of aldosterone synthesis. During angiotensin converting enzyme (ACE) inhibition, the role of alternative major or minor regulatory mechanisms may become significant. This may explain why during continuous ACE inhibition, after an initial reduction, plasma aldosterone measurements may subsequently increase to pretherapeutic levels. In addition to causing sodium and water retention, aldosterone contributes to hypokalaemia and hypomagnesaemia, which may induce electrical instability and death of cardiac myocytes. Aldosterone is also one factor involved in cardiac hypertrophy and fibrosis, which, together with myocardial cell death, may underlie progressive adverse myocardial remodelling. Evidence for a direct vascular effect of aldosterone suggests that this hormone may contribute to generalized vasoconstriction. Elevated plasma aldosterone levels can also contribute to depression of baroreflex sensitivity, and they are associated with increased mortality in patients with severe heart failure. Experimental and clinical research should be further expanded to investigate the potential benefits of opposing the effects of aldosterone by use of specific antagonists or other potentially more potent pharmacological agents with favourable side-effect profiles.

Aldosterone↗

PubMed1995

Practical relevance of the 24-hour trough: peak ratio of antihypertensive drugs.

INTRODUCTION OF THE TROUGH:PEAK RATIO: The mean antihypertensive effect of a drug, measured just before the next dose in a multiple-dose regimen, is generally used as a criterion for approval by regulatory agencies. However, for many short-acting drugs very high doses may be required to maintain some antihypertensive activity at the end of the dosing interval. This may lead to an excessive reduction in blood pressure at the time of peak drug effect. In order to avoid unnecessarily large doses, regulatory agencies have introduced a new standard, the trough:peak ratio, which may be 50-60% but should should ideally be higher. BENEFITS OF HIGH TROUGH:PEAK RATIO: A high trough:peak ratio indicates a long duration of action. This may provide a better risk:benefit ratio compared to shorter acting antihypertensive agents by giving optimal therapeutic coverage for 24 h or even longer. Greater benefit may be gained from better control of overnight blood pressure, especially in the early morning hours when both a steep rise in blood pressure and a higher rate of cardiovascular events have been observed. Large swings in blood pressure may occur when the peak is too high in relation to the trough, increasing blood pressure variability, which may in turn increase target organ damage. A high trough:peak ratio may protect the patient against drug-induced blood pressure fluctuations. It may also produce fewer adverse effects as the blood pressure may fall further and the onset of action may be more gradual. This, together with an effective single daily dose, may increase patient compliance. Furthermore, an antihypertensive effect that lasts more than 24 h protects the patient against a rapid loss of blood pressure control when a dose is omitted or delayed. TROUGH:PEAK RATIO OF AVAILABLE ANTIHYPERTENSIVE DRUGS: We performed a literature survey to evaluate the practical relevance of the trough:peak ratio and to determine how it might help in the choice of antihypertensive agents. The results suggested that not all single daily doses of angiotensin converting enzyme inhibitors or calcium antagonists had a trough:peak ratio of > 50%. We conclude that specially designed, prospective clinical trials should be conducted to address this issue.

Antihypertensive Agents↗

PubMed1994

[Antihypertensive efficacy and tolerability of diltiazem and enalapril, alone or in combination. DESG. Diltiazem Enalapril Study Group].

OBJECTIVES: Since conversion enzyme inhibitors and calcium inhibitors may have synergic actions, we evaluated the antihypertensive effect and tolerance of prolonged-release diltiazem (300 mg/d) and enalapril (20 mg/d). METHODS: A double blind study included 176 patients with mild to moderate hypertension. Diltiazem was given to 89 (44 males, 45 females, mean age 49.91 +/- 10.50 years, mean resting diastolic arterial pressure 103 +/- 5 mmHg) and 87 (49 males, 38 females, mean age 51.37 +/- 12.13 years, mean resting diastolic arterial pressure 103 +/- 5 mmHg) received enalapril. Single drug therapy was given for 6 weeks and then continued for another 8 weeks in responders. At the end of the first 6-week period non-responders were given a combination regimen (diltiazem 300 mg and enalapril 20 mg). RESULTS: After 6 weeks of single drug therapy, 48 patients in the diltiazem group (61.5%) and 53 in the enalapril group (65.4%) had normal blood pressures which remained normal at the end of the trial 8 weeks later in 36 (76%) and 42 (82%) respectively. After 8 weeks of combined regimen 15 of the 24 non-responders (68%) to single drug diltiazem therapy had normal blood pressures as did 18 of the 23 non-responders (78%) to enalapril alone. Tolerance evaluated clinically, biologically and electrocardiographically was comparable to reports in the literature. CONCLUSION: Delayed prolonged-release diltiazem 300 mg and enalapril 20 mg thus had equivalent antihypertensive effects and were equally well tolerated. Combination therapy increased effectiveness without inducing any additional side effects.

Adult↗

PubMed1994

Contribution of specific skeletal muscle metabolic abnormalities to limitation of exercise capacity in patients with chronic heart failure: a phosphorus 31 nuclear magnetic resonance study.

Several studies of phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) have demonstrated the presence of skeletal muscle metabolic abnormalities during exercise in patients with chronic heart failure (CHF). We studied the contribution of these abnormalities to the limitation of exercise capacity in CHF. In 25 patients (age 57 +/- 2 years, left ventricular ejection fraction [LVEF] 28% +/- 1.6%, peak oxygen consumption (VO2) 16 +/- 1.2 ml/kg/mm) (mean +/- SEM), we studied the calf muscle at rest and during plantar flexion with 31P MRS. The phosphocreatine (PCr) depletion rate was significantly negatively correlated to peak VO2 (r = -0.62, p = 0.001) but not to LVEF. Muscle pH was correlated with the inorganic phosphorus (Pi)/PCr ratio (r = -0.69, p = 0.0001) and with the PCr/adenosine triphosphate beta (ATP beta) ratio (which negatively relates to adenosine diphosphate [ADP] concentration) (r = 0.65, p = 0.00001). Although muscle ATP (ATP/sum of phosphorus [sigma P] remained stable, in 8 patients ATP/sigma P decreased significantly (-15% +/- 4%, p = 0.0002). In this ATP-depleted group, peak VO2 was significantly lower than that of the nondepleted group and PCr depletion more rapid, whereas LVEF did not differ. Skeletal muscle metabolic abnormalities in CHF contribute markedly to the alteration of exercise capacity. Rapid PCr depletion and muscle acidosis are the most relevant abnormalities. ATP depletion and excessive increase in ADP during exercise may contribute further to exercise limitation specifically in patients with more marked CHF.

Adenosine Diphosphate↗

PubMed1994

Can anaerobic threshold be used as an end-point for therapeutic trials in heart failure? Lessons from a multicentre randomized placebo-controlled trial. The VO2 French Study Group.

Anaerobic threshold (AT), proposed as a non-invasive index of exercise tolerance, independent of patient motivation, is considered more reliable than exercise duration in assessing the effect of drug therapy in chronic heart failure (CHF). However, inter-observer variation in patients may be more difficult than in normal subjects. In a multicentre study, 85 patients from 10 centres performed a total of 331 bicycle maximal tests (ramp protocols, 10 watts.min-1) with respiratory gas analysis by different systems. A central committee reviewed all the tests. Percentages of AT determination ranged from 34% to 71% depending on the method used. Apart from the respiratory exchange ratio (RER) method, which yielded the lowest rate of determination: 34%, and the crossing point (when RER = 1), which yielded the highest rate, 71%, other methods of determination, such as carbon dioxide (42%), minute ventilation (52%) or ventilatory equivalents plotted vs time (57%), did not differ in the rate of AT determination. Thus, even among trained physicians, AT determination was not reliable. The crossing point may nevertheless be a valuable index from a pragmatic standpoint, although it occurs after the actual AT. Peak oxygen uptake should remain the main end-point in assessment of exercise capacity.

Anaerobic Threshold↗

PubMed1994

Skeletal muscle phosphate metabolism abnormalities in volume-overload experimental heart failure.

We studied skeletal muscle phosphate metabolism abnormalities to examine their contribution at an early stage of congestive heart failure (CHF) in rats with aortocaval fistula (ACF) 4 wk after the procedure. In a group of 26 rats (13 with ACF and 13 sham operated), we assessed the degree of CHF. The ACF produced a significant rise in heart weight and plasma atrial natriuretic peptide. In a second group of 26 rats (13 ACF and 13 sham operated), we performed 31P-magnetic resonance spectroscopy in the gastrocnemius muscle during motor activity produced by electrical stimulation. The rate of phosphocreatine depletion, expressed by its initial slope, was higher in the ACF rats compared with controls (0.078 +/- 0.01 vs. 0.041 +/- 0.007; P < 0.03). pH and ATP decreased and phosphodiesters increased in all rats during electrical stimulation, with no difference between ACF rats and controls. The kinetics of phosphocreatine recovery were not different between ACF rats and controls. Together with previous studies, our present results suggest that muscle metabolism abnormalities in CHF may vary according to the experimental model and may be observed early in the course of the disease.

Adenosine Triphosphate↗

PubMed1994

[Metabolic, morpho-histologic and biochemical changes in skeletal muscles in chronic cardiac failure].

The study of skeletal muscle by nuclear magnetic resonance (NMR) 31p in patients with chronic heart failure (CHF) or in experimental animal models has not shown metabolic abnormalities under basal conditions. However, during exercise, phosphocreatinine (PCr) depletion is increased and early intracellular acidosis has been demonstrated. These changes contribute to deterioration of exercise capacity as they are related to peak VO2 and exercise duration. Other metabolites may play an important role. The depletion of ATP at maximal exercise may be observed in some patients with severe CCF. The results of PCr recovery kinetics are contradictory. Apparently, its recovery rate is unchanged. Most biochemical and histological abnormalities are represented by a decrease in oxidative structure (type I muscular fibres, mitochondria) and in enzymatic oxidative capacity. These changes are related to the metabolic abnormalities and exercise capacity. Muscular hypotrophy alone cannot explain the metabolic changes observed in CHF. Several mechanisms could be involved, physical deconditioning probably being the most pertinent. Other factors such as neurohormonal activation and insulin resistance should be investigated. Physical training improves exercise capacity and may reverse these muscular abnormalities. A long-term benefit of physical training on morbidity and mortality should be demonstrated.

Acidosis↗

PubMed1993

Angiotensin-converting enzyme inhibitor and spironolactone combination therapy. New objectives in congestive heart failure treatment.

Secondary aldosteronism has deleterious effects in patients with congestive heart failure (CHF) and can contribute to congestion, ventricular arrhythmias, and sudden death. Mortality is higher in patients with elevated levels of plasma aldosterone. Aldosterone increases as CHF progresses as a result of activation of the renin-angiotensin-aldosterone system (RAAS). This is further amplified by the routine use of diuretics. Angiotensin-converting enzyme (ACE) inhibitors produce a profound and consistent inhibition of angiotensin II production, but they exert only a mild and transient antialdosterone effect. In a number of studies involving ACE inhibitors, plasma aldosterone levels at the end of the trial do not differ significantly from baseline. Spironolactone, a specific aldosterone receptor antagonist, may exert an independent and additive effect to that of ACE inhibitors. Apart from its renal effects, recent evidence suggests that spironolactone may exert direct cardiac and vascular effects inhibiting cardiac collagen hypertrophy and limiting vascular constriction. Combining an ACE inhibitor and spironolactone may achieve a more complete inhibition of the whole RAAS and may produce further clinical benefits. The efficacy and safety of such a combination has not been properly addressed. In the CONSENSUS trial, plasma potassium and creatinine levels were not necessarily adversely affected when enalapril was added to the regimens of patients receiving spironolactone, a condition existing in > 40% of the patients enrolled in this study. One prospective open study and other anecdotal reports suggest that combining spironolactone and ACE inhibitors resulted in clinical improvement without serious side effects in patients who could not tolerate further increases in the ACE inhibitor dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1993

Effects of lisinopril and hydrochlorothiazide on platelet function and blood rheology in essential hypertension: a randomly allocated double-blind study.

AIM: To compare the effects of an angiotensin converting enzyme (ACE) inhibitor and a thiazide diuretic on platelet function and haemorrheological variables, since these factors may contribute to the atherosclerotic and thrombotic complications associated with hypertension. METHODS: Following a 2-week placebo period, 80 male and female patients with mild to moderate hypertension, aged 50 +/- 10 (mean +/- SD) years, were randomly allocated in a double-blind study to 4 weeks of treatment with the ACE inhibitor lisinopril at 20 mg once a day or the diuretic hydrochlorothiazide at 25 mg once a day. Venous blood was sampled before and at the end of the 4-week treatment period to assess platelet function and haemorrheological variables. RESULTS: Both treatments lowered systolic and diastolic blood pressure equally and had no significant effect on platelet counts and platelet aggregation in response to ADP and to arachidonic acid. Haematocrit plasma viscosity and blood filterability were not altered by either drug. Hydrochlorothiazide tended to increase and lisinopril tended to decrease whole blood viscosity at all shear rates but these changes did not reach statistical significance. Lisinopril increased the erythrocyte aggregation time (from 1.98 +/- 0.50 to 2.08 +/- 0.52 s) and decreased the disaggregation shear rate (from 159 +/- 46 to 153 +/- 40 s-1) and the disaggregation shear stress (from 705 +/- 257 to 659 +/- 204 mPa). Hydrochlorothiazide induced the opposite effects (2.00 +/- 0.47 to 1.92 +/- 0.39 s, 181 +/- 531 to 196 +/- 82 s-1 and 813 +/- 268 to 868 +/- 392 mPa, respectively) with a statistically significant (P < 0.05) intergroup difference. CONCLUSIONS: These findings suggest that chronic treatment with the ACE inhibitor lisinopril, but not the diuretic hydrochlorothiazide, may produce favourable effects on blood rheology, but the clinical relevance requires further investigation.

Adult↗

PubMed1993

Trandolapril. How does it differ from other angiotensin converting enzyme inhibitors?

Among the physicochemical, pharmacokinetic and pharmacodynamic properties that differentiate trandolapril from other angiotensin converting enzyme (ACE) inhibitors, the most clinically relevant ones are those that contribute to the long duration of action of the drug. The long elimination half-life of trandolapril and its strong lipophilicity, high ACE inhibitor potency and high affinity for the ACE cause the drug to have a long biological half-life. The long duration of action of trandolapril may be demonstrated experimentally; near total ACE inhibition is observed 24 hours after single dose administration and there is significant ACE inhibition 72 hours following drug withdrawal after long term therapy. We have analysed the duration of blood pressure lowering during long term therapy with commercially available ACE inhibitors in published studies using ambulatory blood pressure monitoring. On the basis of results from 19 studies undertaken in patients with mild to moderate hypertension, it was possible to reconstruct the curve of the magnitude of blood pressure changes against time. Mean trough: peak ratio calculations showed that once-daily administration produced ratios higher than 50% with enalapril (40 to 80%), lisinopril (40 to 70%) and trandolapril (50 to 100%). Other ACE inhibitors had trough: peak ratios lower than 50%. Despite many methodological limitations, this literature analysis demonstrates that trandolapril has a blood pressure-lowering effect for the full 24-hour period. Studies in which a dose is occasionally omitted show that the blood pressure-lowering effect of trandolapril may last beyond 24 hours.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Indapamide reduces hypertensive left ventricular hypertrophy: an international multicenter study.

The effect of 6 months of treatment with indapamide (IND, 2.5 mg/day) on regression of left ventricular hypertrophy (LVH), an independent predictor of poor prognosis in hypertension, was compared by echocardiography to that of nifedipine (NFD, 40 mg/day), enalapril (ENL, 20 mg/day), atenolol (ATL, 100 mg/day), and hydrochlorothiazide (HCTZ, 25 mg/day) in four parallel double-blind studies in 151 hypertensive patients with a diastolic blood pressure between 95 and 120 mm Hg and a raised left ventricular mass index (LVMI) (mg/m2) (Devereux). Patients were randomized to IND or comparator following a 2-week washout (1 month in the IND vs. ATL study). Respective baseline and 6-month LVMI values (mg/m2) were: IND (n = 20) vs. HCTZ (n = 20): 151.4 +/- 6.3 and 125.70 +/- 4.6 (p < 0.001) vs. 141.3 +/- 6.6 and 135.6 +/- 8.3 (p = N.S.); IND (n = 22) vs NFD (n = 19): 144.1 +/- 5.3 and 125.1 +/- 4.3 (p < 0.001) vs. 170.4 +/- 6.6 and 148.2 +/- 6.2 (p < 0.001); IND (n = 9) vs. ENL (n = 9): 155.1 +/- 6.3 and 143.4 +/- 5.2 (p < 0.001) vs. 142.0 +/- 6.7 and 130.0 +/- 5.9 (p < 0.001); IND (n = 17) vs. ATL (n = 12): 146.2 +/- 5.1 and 130.8 +/- 6.5 (p < 0.001) vs. 156.7 +/- 8.4 and 142.9 +/- 10.3 (p < 0.01). All drugs significantly reduced diastolic blood pressure, and all except HCTZ induced a significant and similar reduction in left ventricular mass.

Adult↗

PubMed1992

[Management of the treatment with converting enzyme inhibitors in chronic heart failure].

Treatment with angiotensin-converting enzyme (ACE) inhibitors can begin at any time when a left ventricular dysfunction has been diagnosed. In the absence of rare contra-indications (renal artery stenosis, connective tissue disease, severe renal failure), all patients with asymptomatic or, a fortiori, symptomatic chronic heart failure can benefit from ACE inhibitors, whatever the origin of the heart failure. Among the ACE inhibitors now available, the benefits of captopril (3 daily doses) and of enalapril (2 daily doses) on all the targets of cardiac failure treatment are now well established. The effects of lisinopril on mortality are not yet known, but the haemodynamic and symptomatic benefits of this drug are also well established (with the advantage of once daily administration). Other ACE inhibitors with less numerous and less convincing trial reports can be used or rejected depending on the physician's faith in the effects of this pharmaceutical class. With all ACE inhibitors the initial dose must be very low, to be gradually increased over several days or even weeks until the highest dose tolerated is reached. ACE inhibitors can be associated with the classical treatment of cardiac failure. A previous diuretic treatment with sodium depletion may increase the risks of first dose effect and renal intolerance due to the introduction of the ACE inhibitors. Theoretically, the combination of ACE inhibitors and spironolactone is to be avoided for fear of hyperkalaemia and renal deterioration. Yet, provided some precautions are taken this combination may improve the benefits of ACE inhibition when the renin-angiotensin-aldosterone system inhibition is not optimal. However, this has yet to be demonstrated by prospective clinical trials.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Comparison of treatment with lisinopril versus enalapril for congestive heart failure.

The effect of lisinopril 5-20 mg once daily or enalapril 5-20 mg once daily on exercise capacity, ventricular ectopic activity, and signs and symptoms of heart failure have been studied in 278 patients with mild-to-moderate (New York Heart Association [NYHA] classes II and III) heart failure in a randomized, double-blind, parallel-group study of 12 weeks' duration. Exercise duration was significantly increased by both angiotensin-converting enzyme (ACE) inhibitors after 6 and 12 weeks of treatment compared with their respective baseline values. There was a trend toward a greater increase in exercise duration on lisinopril after 12 weeks, although this did not reach statistical significance (p = 0.0748). There were no significant treatment differences with respect to the effect of the 2 drugs on ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Both drugs were equally effective in improving NYHA grading and symptoms. Neither treatment had any significant effect on mean heart rate or mean blood pressures. Both treatments were equally well tolerated. The most commonly reported adverse events on both drugs were cough, dizziness, fall in blood pressure, vertigo, and myocardial infarction. The results of this study indicate that lisinopril 5-20 mg once daily is at least as effective and well tolerated as enalapril 5-20 mg once daily.

Adult↗

PubMed1992

The French multicentre study of ramipril in ambulatory patients with mild-to-moderate hypertension.

The aim of this 16-week trial was to determine the safety and efficacy of a step-care regimen of ramipril, an angiotensin converting enzyme inhibitor, from the minimal active dose (2.5 mg) in patients treated for mild to moderate hypertension. The trial was conducted by 102 general practitioners in 770 patients with mild to moderate hypertension. After a response rate to a 4-week placebo therapy of 9.1%, 57.0% of patients given active treatment with ramipril responded to daily doses of 2.5 mg. Ramipril 5 mg daily was effective in 55.6% of the remaining patients. There was no apparent statistically significant difference between the treatments with ramipril 10 mg or a combination of ramipril 5 mg + Lasix 20 mg daily (44.7% and 47.4% response respectively) in a 6-week double-blind arm of the study. In total, more than 90% of patients responded to treatment with ramipril by the end of the study. The incidence of adverse events was generally low, such as headache, cough, dizziness, asthenia, cramps and nausea. The incidence of cough appeared to be related both to the dosage of ramipril given and to outbreaks of influenza syndrome. Thirty-eight patients discontinued active treatment as a result of minor events such as cough, dizziness or diarrhoea, and one case each of myalgia and papular rash. There were no significant variations in laboratory parameters during the study, especially fasting blood glucose and apolipoprotein A1 and B. The results of this study provide evidence of the safety and efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Blood rheology in arterial hypertension.

DETERMINANTS OF BLOOD RHEOLOGY: Blood flow depends on driving pressure and a resistance factor, the latter being related to geometrical hindrance and to the intrinsic viscosity of the blood. Since whole blood is non-Newtonian in nature, blood viscosity is strongly dependent on shear conditions. Low-shear areas occur in cardiovascular disease, and therefore the interaction between blood viscosity and flow conditions may affect vascular disorders. Increased shear stress secondary to increased viscosity may produce endothelial activation and release of endothelium-derived relaxing factors, leading to flow-dependent vasodilation. All the determinants of blood rheology, including plasma protein and erythrocyte factors may be altered in patients with arterial hypertension. BLOOD RHEOLOGY IN HYPERTENSION: A hyperviscosity state is created which is associated with an unfavourable prognosis, since it is correlated with blood pressure levels and the severity and complications of the disease including left ventricular hypertrophy. The mechanisms of haemorheological abnormalities in hypertension are still unclear. It is not known whether blood rheology is an independent variable in patients with hypertension or whether it is a covariable with other established indices of heterogeneity. However, many aetiopathological changes identified in hypertensive disease may contribute to the observed changes in blood rheology. Haemorheological changes in hypertension, through complex interactions with platelet activation and endothelial function, may contribute to the development of thrombosis and atherosclerosis. Moreover, in acute and chronic ischaemia and other conditions where compensatory mechanisms such as collateral formation and vasodilation are limited, rheological factors may become important determinants of blood flow and tissue oxygenation. TREATMENT EFFECTS: Many antihypertensive agents have direct or indirect potential effects on haemorheological variables. However, to date, most studies that have investigated the effects of therapy on rheological variables have not been performed in clinically relevant situations. Controlled studies that monitor both the acute and longterm effects of antihypertensive drugs on relevant haemorheological variables are required to show whether specific therapeutic approaches can correct abnormalities in blood rheology.

Antihypertensive Agents↗