Metoprolol: a pharmacoeconomic and quality-of-life evaluation of its use in hypertension, post-myocardial infarction and dilated cardiomyopathy

Metoprolol is a beta 1-selective adrenoceptor antagonist that is widely used in several indications. A recent investigation has also highlighted a potential role for metoprolol in selected patients with idiopathic dilated cardiomyopathy. Pharmacoeconomic and quality-of-life data for metoprolol are limited to the areas of hypertension, post-myocardial infarction and idiopathic dilated cardiomyopathy. In these settings, metoprolol has shown beneficial effects on morbidity and mortality, or closely-related end-points. Controlled release formulations offer the potential to maximise the confirmed antihypertensive benefits of metoprolol by maintaining clinically effective plasma drug concentrations within a narrow range over a 24-hour interval between doses. Recent data support the use of controlled release metoprolol at the low dose of 50 mg/day. Metoprolol is at least as effective as many other antihypertensive drugs, although compared with thiazide diuretics at relatively high doses in the MAPHY (Metoprolol Atherosclerosis Prevention in Hypertensives) trial, metoprolol was associated with a more favourable effect on mortality. Pharmacoeconomic analysis, also based on the MAPHY trial, indicates that metoprolol is more cost effective than high dose thiazide diuretics in middle-aged men with mild to moderate hypertension. However, the advantage for beta-blockade in this trial is not supported by results of other studies, and the applicability of these data to current medical practice using lower thiazide doses is therefore questionable. Quality of life in patients with mild to moderate hypertension did not deteriorate in most investigations with metoprolol. Furthermore, quality of life was similar for controlled release metoprolol and atenolol. With conventional/matrix-based sustained release metoprolol, quality of life was less satisfactory than with lisinopril but was only marginally different from that with diltiazem (at lower than usual therapeutic doses). Nevertheless, these newer agents have no proven beneficial effect on mortality, and further studies are also warranted with controlled release metoprolol 50 mg/day. When administered post-myocardial infarction, conventional metoprolol was associated with significant improvements in quality of life and was cost saving over a 3-year period. Significant improvements in quality of life were also evident for metoprolol-treated patients with idiopathic dilated cardiomyopathy. In summary, available data support the continued extensive usage of metoprolol as treatment for hypertension and as therapy post-myocardial infarction. Pharmacoeconomic data supporting an advantage for metoprolol over high dose thiazides in hypertension needs further assessment in settings reflecting usual general practice approaches to managing patients with hypertension, while differences in quality of life between metoprolol and other antihypertensive agents appear to be marginal.(ABSTRACT TRUNCATED AT 400 WORDS)     

Beta-blockers and primary cardioprotection in hypertension

Theoretical and experimental data coupled with findings from several studies, showing the beneficial effect of beta-blocking therapy in reducing the risk of death and re-infarction among infarct patients (secondary cardioprotection), suggested that beta-blockers could reduce the incidence of coronary events also in hypertensive patients with no clinical evidence of coronary heart disease (CHD) (primary cardioprotection). In order to evaluate the primary cardioprotective potential of beta-blockers as compared to diuretics in the treatment of hypertension, some large-scale, randomized, prospective studies were set up in the middle and late 1970s. The results of three of these trials, the MRC, the IPPPSH and the HAPPHY studies, were negative or non-conclusive and somehow conflicting. None of them showed any difference between beta-blockers and diuretics in reducing the incidence of CHD, but the MRC and the IPPPSH studies suggested that beta-blockers were better than diuretics in male non-smokers. However, the HAPPHY study did not confirm such a hypothesis. More recently, two studies, the Clatterbridge study (retrospective, non-controlled) and the MAPHY study (prospective, controlled) gave positive results about the primary cardioprotective effect of beta-blockers. In particular, the MAPHY study demonstrated that starting antihypertensive treatment with the beta1-selective beta-blocker metoprolol instead of a thiazide diuretic led to lower total and cardiovascular mortality, mainly by reducing fatal CHD and fatal stroke. Although more evidence is needed, the primary cardioprotective effect demonstrated with metoprolol in the MAPHY study might have important implications for clinical practice and public health.     

Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders

During the intervening years since metoprolol was first reviewed in the Journal (1977), it has become widely used in the treatment of mild to moderate hypertension and angina pectoris. Although much data have accumulated, its precise mechanisms of action in these diseases remain largely uncertain. Optimum treatment of hypertension and angina pectoris with metoprolol is achieved through dose titration within the therapeutic range. It has been clearly demonstrated that metoprolol is at least as effective as other beta-blockers, diuretics and certain calcium antagonists in the majority of patients. Although a twice daily dosage regimen is normally used, satisfactory control can be maintained in many patients with single daily doses of conventional or, more frequently, slow release formulations. Addition of a diuretic may improve the overall response rate in hypertension. Several controlled trials have studied the effects of metoprolol administered during the acute phase and after myocardial infarction. In early intervention trials a reduction in total mortality was achieved in one moderately large trial of prolonged treatment, but in another, which excluded patients already being treated with beta-blockers or certain calcium antagonists and where treatment was only short term, mortality was significantly reduced only in 'high risk' patients. Overall results with metoprolol have not demonstrated that early intervention treatment in all patients produces clinically important improvement in short term mortality. Thus, the use of metoprolol during the early stages of myocardial infarction is controversial, largely because of the requirement to treat all patients to save a small number at 'high risk'. This blanket coverage approach to treatment may be more justified during the post-infarction follow-up phase since it has been shown that metoprolol slightly, but significantly, reduces the mortality rate for periods of up to 3 years. Metoprolol is generally well tolerated and its beta 1-selectivity may facilitate its administration to certain patients (e.g. asthmatics and diabetics) in whom non-selective beta-blockers are contraindicated. Temporary fatigue, dizziness and headache are among the most frequently reported side effects. After a decade of use, metoprolol is well established as a first choice drug in mild to moderate hypertension and stable angina, and is beneficial in post-infarction patients. Further study is needed in less well established areas of treatment such as cardiac arrhythmias, idiopathic dilated cardiomyopathy and hypertensive cardiomegaly.     

Metoprolol: a review of its use in chronic heart failure

Metoprolol, a relatively selective beta1-blocker, is devoid of intrinsic sympathomimetic activity and possesses weak membrane stabilising activity. The drug has an established role in the management of essential hypertension and angina pectoris, and more recently, in patients with chronic heart failure. The effects of metoprolol controlled-release/extended-release (CR/XL) in patients with stable, predominantly mild to moderate (NYHA functional class II to III) chronic heart failure have been evaluated in the large Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) trial and the much smaller Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study. Treatment with metoprolol CR/XL was initiated at a low dosage of 12.5 to 25 mg once daily and gradually increased at 2-weekly intervals until the target dosage (200 mg once daily) or maximal tolerated dosage had been attained in patients receiving standard therapy for heart failure. At 12 months, metoprolol CR/XL was associated with a 34% reduction in relative risk of all-cause mortality in patients with chronic heart failure due to ischaemic or dilated cardiomyopathy in the MERIT-HF trial. The incidence of sudden death and death due to progressive heart failure were both significantly decreased with metoprolol CR/XL. Similarly, a trend towards decreased mortality in the metoprolol CR/XL group compared with placebo was observed in the RESOLVD trial. Data from small numbers of patients with severe (NYHA functional class IV) heart failure indicate that metoprolol CR/XL is effective in this subset of patients. However, no firm conclusions can yet be drawn. Improvement from baseline values in NYHA functional class, exercise capacity and some measures of quality of life with metoprolol CR/XL or immediate-release metoprolol were significantly greater than those with placebo. The drug is well tolerated when treatment is initiated in low dosages and gradually increased at intervals of 1 to 2 weeks. Conclusions: Metoprolol CR/XL effectively decreases mortality and improves clinical status in patients with stable mild to moderate (NYHA functional class II or III) chronic heart failure due to left ventricular systolic dysfunction, and the drug is effective in patients with ischaemic or dilated cardiomyopathy. Although limited data indicate that metoprolol CR/XL is effective in patients with severe (NYHA functional class IV) chronic heart failure, more data are needed to confirm these findings. Treatment with metoprolol CR/XL significantly reduced the incidence of sudden death and death due to progressive heart failure.     

A controlled study on the antihypertensive effect of a new beta-adrenergic receptor blocking drug, metoprolol, in combination with chlorthalidone

1. A double-blind crossover evaluation of the antihypertensive effect of metoprolol v. placebo was carried out in a series of twenty-three patients with mild or moderate essential hypertension who were receiving chlorthalidone (25 mg daily) as their basic treatment. An individually titrated metoprolol dosage (75-300 mg) was used. The double-blind crossover study consisted of two 3-month periods during which the patients received either metoprolol or placebo in addition to chlorthalidone.

2 Metoprolol, as compared with placebo, produced a statistically significant reduction of blood pressure, both in supine and standing positions. Normotension was achieved during metoprolol-chlorthalidone treatment in twenty-two of the twenty-three patients, but during placebo-chlorthalidone treatment in only twelve of the twenty-three patients.

3 During the double-blind crossover study mild side-effects occurred during metoprolol-chlorthalidone treatment in fourteen patients during first month, in twelve patients during second month and seven patients during third month. During placebo-chlorthalidone treatment side effects occurred in seven, six and seven patients, respectively.

4 In conclusion, metoprolol caused a significant fall in blood pressure when given to patients already receiving chlorthalidone. Metoprolol in combination with chlorthalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in those patients not responding to chlorthalidone alone.

     

Antihypertensive effect of metoprolol in diuretic-treated,mild primary hypertension

Metoprolol tartrate was administered to 41 patients with mild essential hypertension already treated with a diuretic for a period of 2 weeks. In the majority of those patients, other step 2 antihypertensive agents either failed to control high blood pressure or caused adverse reactions. All other antihypertensive agents except diuretics were discontinued during the 2-week wash-out period. Patients with a diastolic blood pressure of 95 to 104 mmHg (inclusive) received oral metoprolol at a dose of 50mg twice daily for 2 weeks. Subsequently, metoprolol titration was individualized on a bi-weekly basis until either the diastolic blood pressure was = 90 mmHg and/or a maximal daily dose of 300mg of metroprolol was reached. The analysis of efficacy and safety was done for a total period of 14 weeks. Diastolic blood pressure and heart rates were significantly reduced (P≤0.05) in all treatment groups. Minor adverse reactions such as mild fatigue in 11 patients, nervousness in 2, and leg cramps in 2 patients were reported. Transient skin rash, dizziness, headache, chest pain, insomnia, and cold extremities were also reported in one patient each. It is concluded from the present study that metropolol (in twice daily dose) in combination with a diuretic is safe, effective, and well tolerated in the treatment of mild hypertension.     

Carvedilol versus other beta-blockers in heart failure

Carvedilol is a beta-blocker with ancillary properties. Pilot clinical studies with carvedilol, added to the standard therapy of digoxin, diuretics and ACE inhibitors, showed beneficial effects in mild, moderate and severe heart failure. Patients consistently showed improvement in LV ejection fraction and NYHA functional class. Subsequently large clinical trials showed decreased morbidity and mortality with carvedilol in mild and moderate and more recently, severe heart failure. However, there is little or no improvement in exercise tolerance with carvedilol. The beneficial effects of carvedilol in heart failure are associated with cardiac remodelling. Metoprolol and bisoprolol are selective beta(1)-blockers without ancillary properties. Early studies showed benefits with metoprolol and bisoprolol in heart failure. Large clinical trials established that metoprolol and bisoprolol decreased mortality and morbidity in heart failure. In contrast no benefit has been shown with celiprolol, a selective beta(1)-blocker and beta(2)-stimulant in heart failure. There is a debate as to whether the ancillary properties of carvedilol contribute to its beneficial effect in heart failure, making it a better drug to use than metoprolol. Short-term studies suggested that carvedilol and metoprolol were equivalent in heart failure but short-term is probably not an appropriate way to compare the drugs. A recent long-term study and study in poor responders to metoprolol, suggest that carvedilol may be better than metoprolol in heart failure.     

The cost effectiveness of hypertension treatment in Sweden

The aim of this study was to carry out an analysis of the cost effectiveness of antihypertensive drug treatment in different patient groups in Sweden. The cost-effectiveness ratios were estimated as net costs (treatment costs minus reduced costs of cardiovascular morbidity) divided by the number of life-years gained (the increase in life expectancy). The analysis was based on the reduction of coronary heart disease and stroke in the most recent meta-analysis of antihypertensive treatment, to which Swedish cost data were applied. We found that the cost per life-year gained decreases with age for both men and women, and is relatively low for middle-aged and older patients, even when the diastolic blood pressure (DBP) range is 90 to 94mm Hg. In conclusion, the results indicate that, in Sweden, antihypertensive treatment is generally cost effective in middle-aged and older patients with a DBP of > or = 90 mm Hg. However, it is questionable whether it is generally cost effective to treat younger patients with mild hypertension.     

4种血管紧张素Ⅱ受体拮抗药治疗轻中度高血压的成本-效果分析

目的:评价4种血管紧张素Ⅱ受体拮抗药治疗轻中度高血压的成本-效果。方法:104例轻、中度高血压患者分为4组,分别应用替米沙坦、氯沙坦钾、厄贝沙坦、缬沙坦治疗,8wk后比较临床效果并进行成本-效果分析。结果:4种用药方案在疗效比较上差异无统计学意义(P>0·05),成本分别为684·00、760·80、659·20、720·80元,成本-效果比分别为7·74、9·51、7·91、8·07。结论:替米沙坦从药物经济学的角度分析为治疗轻中度高血压的较优药物。     

Carvedilol versus other β-blockers in heart failure

Carvedilol is a β-blocker with ancillary properties. Pilot clinical studies with carvedilol, added to the standard therapy of digoxin, diuretics and ACE inhibitors, showed beneficial effects in mild, moderate and severe heart failure. Patients consistently showed improvement in LV ejection fraction and NYHA functional class. Subsequently large clinical trials showed decreased morbidity and mortality with carvedilol in mild and moderate and more recently, severe heart failure. However, there is little or no improvement in exercise tolerance with carvedilol. The beneficial effects of carvedilol in heart failure are associated with cardiac remodelling. Metoprolol and bisoprolol are selective ₁-blockers without ancillary properties. Early studies showed benefits with metoprolol and bisoprolol in heart failure. Large clinical trials established that metoprolol and bisoprolol decreased mortality and morbidity in heart failure. In contrast no benefit has been shown with celiprolol, a selective ₁-blocker and ₂-stimulant in heart failure. There is a debate as to whether the ancillary properties of carvedilol contribute to its beneficial effect in heart failure, making it a better drug to use than metoprolol. Short-term studies suggested that carvedilol and metoprolol were equivalent in heart failure but short-term is probably not an appropriate way to compare the drugs. A recent long-term study and study in poor responders to metoprolol, suggest that carvedilol may be better than metoprolol in heart failure.     

Arachidonic acid and prostaglandin levels in dithranol erythema: time course study.

Atenolol 100 mg once daily and metoprolol SA 200 mg once daily were compared in 20 patients with mild to moderate hypertension, in a randomised, double-blind cross-over trial. Blood pressure and heart rate were compared at rest and during maximal exercise on a bicycle ergometer at 2 and 24 h post-dose. Blood pressure control was similar with both drugs, except at 2 h when systolic blood pressure was significantly lower with atenolol. Blood pressure and heart rate were less well controlled at 24 h than at 2 h with both drugs, but the majority of patients were still considered adequately controlled at 24 h. Atenolol and metoprolol SA can be considered equally effective in the treatment of mild to moderate hypertension and can be recommended as a once daily regime.     

Controlled release metoprolol formulations. A review of their pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and ischaemic heart disease.

Conventional formulations of metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of hypertension and ischaemic heart disease. Recently developed controlled release metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed to overcome the drug delivery problems of matrix-based sustained release forms by releasing the drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with metoprolol CR/ZOK compared with matrix-based sustained release formulations of metoprolol, or conventional atenolol or bisoprolol, while metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release metoprolol preparations. In patients with stable effort angina pectoris, once daily administration of metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional metoprolol in divided doses, while metoprolol OROS reduced the mean number of anginal attacks by the same margin as atenolol. Controlled release metoprolol formulations have been well tolerated in clinical trials. Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with atenolol or long acting propranolol. Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced bronchoconstrictor effects than atenolol, matrix-based sustained release metoprolol or long acting propranolol in patients with asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of metoprolol in addition to the relatively low plasma concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of metoprolol, the use of all beta-adrenoceptor antagonists should be avoided in patients with a history of bronchospasm. Thus, controlled release metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.     

Hydrochlorothiazide versus spironolactone: long-term metabolic modifications in patients with essential hypertension

The metabolic side effects of thiazide diuretics are believed to be responsible for the failure of thiazide diuretics to reduce cardiovascular morbidity in patients with hypertension. However, the decrease in the incidence of osteoporotic fractures that are associated with thiazide administration may be relevant in elderly patients with arterial hypertension. Spironolactone (SP) appears not to influence the metabolic risk profile of the patient with hypertension, and no studies have examined its effect on calcium metabolism. Therefore, in 22 patients with mild to moderate essential hypertension, the authors performed a parallel, randomized, double-blind, placebo-controlled study that compared the effects on serum urate and lipid, potassium, magnesium, and calcium metabolism of hydrochlorothiazide (HC) (mean [+/- SD] dose, 72 +/- 26 mg/d) and SP (144 +/- 53 mg/d) during a 52-week period. As compared with placebo, HC significantly increased serum urate and total cholesterol concentrations, and decreased serum potassium levels. SP did not affect serum urate or cholesterol levels but increased serum potassium concentrations. Neither diuretic significantly modified magnesium metabolism. Little changes were seen in serum calcium levels during HC or SP treatment, whereas urinary calcium excretion was significantly decreased by HC (mean decrease, 45%; P less than .01) or SP (40%; P less than .01). The authors conclude that SP, in addition to its potassium-sparing properties, has a calcium-sparing effect that may be beneficial for patients in whom reduction of urinary calcium excretion has a therapeutic value.     

糖尿病合并高血压的可能机制和降压药选择策略

糖尿病合并高血压使患者心、脑血管事件和终末期肾病的发病危险明显增加。本文简述了糖尿病合并高血压的可能机制,并对糖尿病合并高血压患者的降压药选择进行了复习。目前的总体认识为：血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体阻滞剂、钙通道阻滞剂对糖代谢和糖尿病本身的作用为中性,甚至可产生一定的有益作用;而利尿剂、β受体阻滞剂则可能对糖代谢产生不利影响,特别是当两者合用时,但现有的研究资料尚不能明确证实某一类型降压药具有明显的优越性,因此,无论使用何种药物,使患者的血压迅速、稳定地控制在130/80mmHg以下才是最重要的目标。     

替米沙坦不同联用药方案治疗轻、中度原发性高血压的成本-效果分析

目的:评价替米沙坦不同联用药方案治疗轻、中度原发性高血压的成本-效果。方法:60例患者随机分为3组,分别给予替米沙坦+非洛地平(A组)、替米沙坦+依那普利(B组)、替米沙坦+吲达帕胺(C组)治疗8wk后进行成本-效果分析。结果:A、B、C组总有效率分别为90%、85%、95%;总成本分别为422.80、409.50、348.88元,C组与A、B组比较有显著性差异(P<0.05)。结论:C组方案治疗轻、中度原发性高血压较佳。     

Indapamide. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension

Indapamide is an orally active sulphonamide diuretic agent. Although some evidence appears to indicate that the antihypertensive action of indapamide is primarily a result of its diuretic activity, only a limited diuresis occurs with the usual antihypertensive doses of 2.5 mg daily, and in vitro and in vivo data suggest that it may also reduce blood pressure by decreasing vascular reactivity and peripheral vascular resistance. In mild to moderate hypertension it is as effective as thiazide diuretics and beta-adrenergic blocking agents in lowering blood pressure when used as the sole treatment. Indapamide has been successfully combined with beta-adrenergic blocking agents, methyldopa, and other anti-hypertensive agents. While such findings need confirmation, it appears that indapamide shares the potential with other diuretic agents to induce electrolyte and other metabolic abnormalities, although it may do so with less frequency or severity. Thus, indapamide appears to offer a suitable alternative to more established drugs as a 'first-line' treatment in patients with mild to moderate hypertension. Whether it differs significantly from other diuretics when used as antihypertensive therapy, either in its mode of action or its side effect profile, needs further clarification.     

Issues with antihypertensive therapy: safety perspectives

The benefits of treating hypertension have been documented by several long-term studies that have shown a decreased incidence of morbidity and mortality associated with stroke, left ventricular failure, and renal insufficiency. With the large number of antihypertensive drugs currently available, several safety factors need to be considered when initially choosing a regimen so as not to adversely influence the potential benefits of blood pressure control. Antihypertensive agents should be chosen based on their hemodynamic profile, the absence of adverse metabolic effects and subjective side effects, and the presence of beneficial effects on the patients' quality of life. Thiazide diuretics and beta-blocking agents have often been recommended as initial therapy in patients with mild to moderate hypertension. However, thiazide diuretics may be less desirable in certain patients because of their effects on lipids, potassium, and glucose tolerance; beta-blocking agents are not ideal for some patients because of their effects on lipids, exercise tolerance, and overall quality of life. The angiotensin-converting enzyme inhibitors, selective alpha 1-blocking agents, and calcium channel blocking agents may be more appropriate for initial therapy of hypertension in many patients.     

琥珀酸美托洛尔缓释片治疗原发性高血压60例分析

目的应用琥珀酸美托洛尔缓释片治疗轻、中度原发性高血压,观察其疗效。方法将60位轻、中度原发性高血压病人随机分为两组,每组30人。治疗组用琥珀酸美托洛尔缓释片47.5 mg,每日1次口服,每周随访1次,若2周无效者改用95 mg,每日1次口服4,周为1个疗程;对照组采用苯磺酸氨氯地平2.5～5 mg每日1次口服,每周随访1次4,周为1个疗程。结果治疗组患者,琥珀酸美托洛尔缓释片治疗4周末,治疗前、后血压值及心率比较,差异有统计学著意义(P<0.05);对照组患者治疗前、后血压值及心率比较,差异有统计学意义(P<0.05);将治疗组和对照组用药前、后的心率变化进行比较,前者优于后者,差异有统计学意义(P<0.05)。结论琥珀酸美托洛尔缓释片可持续平稳降压24 h以上,是治疗高血压的有效药物之一。     

Improving Care in Resistant Hypertension

OBJECTIVE: Resistant hypertension is an important clinical problem that is poorly studied and not well managed. The objective of this study was to identify factors associated with successful treatment of resistant hypertension in a specialty clinic. METHODS: This was a retrospective observational study examining the medical records of patients seen at a specialty hypertension clinic at the University of Rochester, Rochester, New York, USA, in the year 2005. The records of 68 patients were reviewed. Those presenting with resistant hypertension (defined as BP > or =140/90mm Hg and receiving at least three antihypertensive medications, including a diuretic) were identified. Change in medication type and dosage, BP reduction, and percentage of patients at Joint National Committee (JNC)-7 goal were noted. RESULTS: Twenty-eight patients were included in the analysis. Mean age was 62.5 +/- 11.6 years, 54% were women, and mean presenting BP was 175.4 +/- 23.5/87.5 +/- 14.6mm Hg. After an average of 6.2 +/- 3.2 visits over a mean of 13.9 +/- 13.5 months, mean BP was reduced to 145.3 +/- 27.7/73.9 +/- 13.6mm Hg (paired t-test: p = 0.001 SBP, p = 0.0001 DBP), and 44.8% of the patients were at their JNC-7 goal. Change in the mean number of antihypertensive medications was not significantly different between the initial and final clinic visits (4.1 +/- 1.2 vs 4.2 +/- 1.0; p = 0.627). Combination pill use increased from four patients (14%) at initial visit to 19 (68%) at final visit. Numbers of patients treated with diuretics, beta-adrenoceptor antagonists, calcium channel antagonists (CCB), and minoxidil increased at the final clinic visit. Significant dose-related changes included the up-titration of CCBs to high doses, and the initiation of moderate doses of thiazide diuretics; mainly chlorthalidone (67% final visit vs 0% at initial visit). CONCLUSIONS: Patients referred to a specialty clinic for the control of resistant hypertension achieved significant reductions in BP with frequent visits, combination pills, and greater use and higher doses of CCBs and thiazide diuretics.     

The use of diuretics in modern antihypertensive therapy

Abstract: A review is made to sum up the indications when diuretics may be the drug of choice in the treatment of hypertension. Advantages from the combined treatment of thiazide diuretics and other antihypertensive agents are also emphasized. Adverse effects from diuretic treatment, i. e. hypokalemia, hyperuricemia, impaired glucose tolerance and risks associated with unfavourable serum lipoprotein patterns are discussed. It is concluded that from a hemodynamic point of view thiazide diuretics can be a good therapeutic alternative for most patients, excepting those with hyperkinetic circulation. It is recommended to use lower doses of thiazide diuretics than previously and the monitoring of S-potassium is necessary in all patients.