A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: A UK perspective.

Thiazide diuretics have been the cornerstone of hypertension treatment for >5 decades. Most recent European and American guidelines recommend both thiazide-type and thiazide-like diuretics as first-line drugs for all patients with hypertension. In contrast, diuretics are not regarded as first-line treatment in the UK and in patients who are to be initiated on a diuretic treatment, thiazide-like molecules, such as chlortalidone and indapamide are the preferred option. This review examines the prescribing trend of the 4 most commonly prescribed thiazide diuretics for the treatment of hypertension in the UK. Prescription cost analysis data were obtained for both 2010 and 2016/2017 for each region of the UK to analyse the impact of the 2011 National Institute for Health and Care Excellence hypertension guidelines on the trend in thiazide diuretic prescribing. Overall, the prescriptions of thiazide diuretics declined over the years. Bendroflumethiazide is the most commonly prescribed diuretic in the UK and despite some geographical differences, thiazide-type diuretics are more widely used than thiazide-like. The use of indapamide increased significantly between 2010 and 2016/2017 while chlortalidone was rarely employed. Of the many factors affecting trends in prescriptions, clinical inertia, treatment adherence, availability of the products and the lack of fixed dose combinations may play a role.

Pharmacotherapy for hypertension in adults aged 18 to 59 years.

BACKGROUND: Hypertension is an important risk factor for adverse cardiovascular events including stroke, myocardial infarction, heart failure and renal failure. The main goal of treatment is to reduce these events. Systematic reviews have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older. We wanted to know what the effects of therapy are in people 18 to 59 years of age. OBJECTIVES: To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension. To quantify effects on cardiovascular mortality plus morbidity (including cerebrovascular and coronary heart disease mortality plus morbidity), withdrawal due adverse events and estimate magnitude of systolic blood pressure (SBP) and diastolic blood pressure (DBP) lowering at one year. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to January 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. SELECTION CRITERIA: Randomized trials of at least one year' duration comparing antihypertensive pharmacotherapy with a placebo or no treatment in adults aged 18 to 59 years with mild to moderate primary hypertension defined as SBP 140 mmHg or greater or DBP 90 mmHg or greater at baseline, or both. DATA COLLECTION AND ANALYSIS: The outcomes assessed were all-cause mortality, total cardiovascular (CVS) mortality plus morbidity, withdrawals due to adverse events, and decrease in SBP and DBP. For dichotomous outcomes, we used risk ratio (RR) with 95% confidence interval (CI) and a fixed-effect model to combine outcomes across trials. For continuous outcomes, we used mean difference (MD) with 95% CI and a random-effects model as there was significant heterogeneity. MAIN RESULTS: The population in the seven included studies (17,327 participants) were predominantly healthy adults with mild to moderate primary hypertension. The Medical Research Council Trial of Mild Hypertension contributed 14,541 (84%) of total randomized participants, with mean age of 50 years and mean baseline blood pressure of 160/98 mmHg and a mean duration of follow-up of five years. Treatments used in this study were bendrofluazide 10 mg daily or propranolol 80 mg to 240 mg daily with addition of methyldopa if required. The risk of bias in the studies was high or unclear for a number of domains and led us to downgrade the quality of evidence for all outcomes.Based on five studies, antihypertensive drug therapy as compared to placebo or untreated control may have little or no effect on all-cause mortality (2.4% with control vs 2.3% with treatment; low quality evidence; RR 0.94, 95% CI 0.77 to 1.13). Based on 4 studies, the effects on coronary heart disease were uncertain due to low quality evidence (RR 0.99, 95% CI 0.82 to 1.19). Low quality evidence from six studies showed that drug therapy may reduce total cardiovascular mortality and morbidity from 4.1% to 3.2% over five years (RR 0.78, 95% CI 0.67 to 0.91) due to reduction in cerebrovascular mortality and morbidity (1.3% with control vs 0.6% with treatment; RR 0.46, 95% CI 0.34 to 0.64). Very low quality evidence from three studies showed that withdrawals due to adverse events were higher with drug therapy from 0.7% to 3.0% (RR 4.82, 95% CI 1.67 to 13.92). The effects on blood pressure varied between the studies and we are uncertain as to how much of a difference treatment makes on average. AUTHORS' CONCLUSIONS: Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity. All-cause mortality and coronary heart disease were not reduced. There is lack of good evidence on withdrawal due to adverse events. Future trials in this age group should be at least 10 years in duration and should compare different first-line drug classes and strategies.

The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio.

BACKGROUND: There is continuing variation in diagnosis and estimated prevalence of primary hyperaldosteronism. The higher estimates encourage search for adrenal adenomas in patients with elevated ratios of plasma aldosterone to renin. However, it is more likely that patients with normal plasma K+ and aldosterone belong to the polygenic spectrum of low-renin hypertension rather than have the same monogenic syndrome as classic Conn's. Our primary hypothesis was that in low-renin patients with normal plasma K+ and aldosterone, a thiazide diuretic, bendroflumethiazide, would be as effective as spironolactone in overcoming the Na+ retention and lowering blood pressure. Secondary objectives were to compare the dose response for each diuretic and to evaluate amiloride as an alternative to spironolactone. METHODS AND RESULTS: Fifty-seven patients entered and 51 patients completed a placebo-controlled, double-blind, randomized crossover trial. Entry criteria included low plasma renin, normal K+, elevated aldosterone-renin ratio, and a previous systolic blood pressure response to spironolactone of > or = 20 mm Hg. Two doses each of spironolactone and bendroflumethiazide were compared. The crossover also included amiloride and losartan. Outcome measures were blood pressure, plasma renin, and other biochemical markers of diuretic action. Spironolactone 100 mg and bendroflumethiazide 5 mg caused similar falls in systolic blood pressure, whereas bendroflumethiazide 2.5 mg was 5/2 mm Hg less effective in reducing blood pressure than either bendroflumethiazide 5 mg or spironolactone 50 mg (P<0.005). Amiloride 40 mg was as effective as the other diuretics. Biochemical indices of natriuresis showed bendroflumethiazide to be less effective than either spironolactone or amiloride; plasma renin rose 4-fold on spironolactone but only 2-fold on bendroflumethiazide (P=0.003). CONCLUSIONS: In hypertensive patients with a low plasma renin but normal K+, bendroflumethiazide 5 mg was as effective as spironolactone 100 mg in lowering blood pressure, despite patients being selected for a previous large fall in blood pressure on spironolactone. Because this result differs from that expected in primary hyperaldosteronism, our finding argues against low-renin hypertension including a large, undiagnosed pool of primary hyperaldosteronism. However, spironolactone was the more effective natriuretic agent, suggesting that inappropriate aldosterone release or response may still contribute to the Na+ retention of low-renin hypertension.

STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation.

OBJECTIVE: Older people experience more concurrent illnesses, are prescribed more medications and suffer more adverse drug events than younger people. Many drugs predispose older people to adverse events such as falls and cognitive impairment, thus increasing morbidity and health resource utilization. At the same time, older people are often denied potentially beneficial, clinically indicated medications without a valid reason. We aimed to validate a new screening tool of older persons' prescriptions incorporating criteria for potentially inappropriate drugs called STOPP (Screening Tool of Older Persons' Prescriptions) and criteria for potentially appropriate, indicated drugs called START (Screening Tool to Alert doctors to Right, i.e. appropriate, indicated Treatment). METHODS: A Delphi consensus technique was used to establish the content validity of STOPP/START. An 18-member expert panel from academic centers in Ireland and the United Kingdom completed two rounds of the Delphi process by mail survey. Inter-rater reliability was assessed by determining the kappa-statistic for measure of agreement on 100 data-sets. RESULTS: STOPP is comprised of 65 clinically significant criteria for potentially inappropriate prescribing in older people. Each criterion is accompanied by a concise explanation as to why the prescribing practice is potentially inappropriate. START consists of 22 evidence-based prescribing indicators for commonly encountered diseases in older people. Inter-rater reliability is favorable with a kappa-coefficient of 0.75 for STOPP and 0.68 for START. CONCLUSION: STOPP/START is a valid, reliable and comprehensive screening tool that enables the prescribing physician to appraise an older patient's prescription drugs in the context of his/her concurrent diagnoses.

Effects of "newer" and "older" antihypertensive drugs on hemorrheological, platelet, and endothelial factors. A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.

BACKGROUND: Different antihypertensive therapies may exert benefits via not only a reduction in blood pressure but also in improving the risk of thrombosis. METHODS: We tested the hypothesis that a more modern antihypertensive drug regimen (ie, amlodipine +/- perindopril) would have a more beneficial effect on hemorheological markers (white blood-cell count [WCC], plasma viscosity [PV], hematocrit [HCT], and fibrinogen)--and on plasma von Willebrand factor (vWf, an index of endothelial damage and dysfunction) and soluble P-selectin (sP-sel, an index of platelet activation), compared with an older antihypertensive drug regimen (ie, atenolol +/- bendroflumethiazide). RESULTS: After 6 months, PV, sP-sel, and HCT fell in both groups (P < .01), while fibrinogen was unchanged. However, those 74 patients randomized to amlodipine +/- perindopril had significant reductions in WCC (P = .005), with no significant changes in vWF or platelet count. Conversely, in those 85 patients randomized to atenolol +/- bendroflumethiazide, there were significant reductions in vWF (P = .001) and platelet count (P = .011) but no significant reductions in WCC. There were no significant differences in the levels of any of the variables between the two arms of the trial, nor a significant difference in the magnitude of reduction between the two treatment arms. CONCLUSIONS: Within the constraints of this substudy design, there was no differential effect apparent of the two antihypertensive treatment arms on hemorheological parameters or endothelial and platelet function (as assessed by vWF and sP-sel), suggesting that other pathophysiological mechanisms may be involved.

Does the aldosterone:renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study.

BACKGROUND: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT1study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study. The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting. METHODS/DESIGN: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios. Primary Objective--To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios. Secondary Objectives--To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide. DISCUSSION: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.

Delayed cardiotoxicity in chronic lithium poisoning: discrepancy between serum lithium concentrations and clinical status.

Chronic lithium poisoning is characteristically associated with greater toxicity than acute ingestion. Neurotoxic features may occur within several hours, whereas major cardiovascular effects are typically not seen until later. This report describes profound bradycardia as a late consequence of chronic lithium poisoning, and reminds us to consider the possibility of delayed toxic effects, even in situations where serum lithium concentrations appear to be declining.

Hypokalaemia and drinking green tea: a literature review and report of 2 cases.

We report the association between excessive consumption of green tea and hypokalaemia in an Oriental couple. Both patients were asymptomatic and the abnormal electrolyte level was only detected on routine blood tests. When they were advised to reduce the consumption of green tea, the abnormally low potassium level was reversed. We have not found such an association reported in the medical literature. The health benefits of green tea consumption are well publicised but the potential side-effects of overconsumption are less well known. We would like to report this association to alert clinicians about this potentially serious complication. This is especially relevant for those who are also taking prescribed medications that can lower potassium levels and/or sensitise patients to potential harm from hypokalaemia.

Acute renal failure and arterial hypertension due to subcapsular haematoma: is percutaneous drainage a feasible treatment?

Percutaneous drainage proved to be successful in managing a renal subcapsular haematoma that was causing acute renal failure and hypertension in a 74-year-old woman. The patient presented with oliguria, nausea and malaise 2 days after a ureteronephroscopic procedure with biopsies of a suspected urothelial neoplasm in the right renal pelvis. The left kidney had recently been removed due to renal cell carcinoma. At admission, the patient's blood pressure and plasma creatinine levels were massively elevated. Ultrasonography revealed a moderate right-sided renal subcapsular haematoma. When the patient did not respond to antihypertensive treatment, Page kidney was suspected. A pigtail catheter was placed in the haematoma and, shortly after drainage, the diuresis resumed and plasma creatinine together with blood pressure decreased. This condition had previously been managed by open surgery, but recent case reports have described successful management by laparoscopy-assisted and radiology-assisted drainage, as described in this case report.

Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study.

BACKGROUND: Vascular endothelial dysfunction may predict future atherosclerosis. Hence, an antihypertensive agent that reverses endothelial dysfunction and lowers blood pressure might improve the prognosis of patients with hypertension. We hypothesized that nebivolol, a vasodilating beta-blocker, could improve endothelial dysfunction. We tested this hypothesis by comparing the effects of nebivolol and atenolol on endothelial function. METHODS AND RESULTS: Twelve hypertensive patients with a mean ambulatory blood pressure of 154+/-7/97+/-10 mm Hg were randomized after a 2-week placebo run-in period (baseline) in a double-blind, crossover fashion to 8-week treatment periods with either 5 mg of nebivolol with 2.5 mg of bendrofluazide or 50 mg of atenolol with 2.5 mg of bendrofluazide. Forearm venous occlusion plethysmography and intra-arterial infusions of acetylcholine and N(G)-monomethyl-L-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide release, respectively. Sodium nitroprusside was used as an endothelium-independent control. Nebivolol/bendrofluazide and atenolol/bendrofluazide each lowered the clinic blood pressure to the same extent (132+/-7/82+/-6 and 132+/-9/83+/-8 mm Hg, respectively; P<0.001 from baseline). The vasodilatory response to acetylcholine was significantly increased with nebivolol/bendrofluazide (maximum percentage change in forearm blood flow [mean+/-SEM], 435+/-27%, P<0.001) but not with atenolol/bendrofluazide. Similarly, the endothelium-dependent vasoconstrictive response to L-NMMA was significantly improved only with nebivolol treatment (percentage change in forearm blood flow, -54+/-5%; P<0.001). The response to sodium nitroprusside was not different between treatments, suggesting that the endothelium-independent pathway was unaffected. CONCLUSIONS: Nebivolol/bendrofluazide increased both stimulated and basal endothelial nitric oxide release, whereas for the same degree of blood pressure control, atenolol/bendrofluazide had no effect on nitric oxide bioactivity. Thus, nebivolol may offer additional vascular protection in treating hypertension.

Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone?

BACKGROUND: The recognition that some 10% to 15% of the hypertensive population may have aldosterone excess has increased the frequency of measurement of the aldosterone-to-renin ratio (ARR) and the use of aldosterone antagonists. Whether this ratio will predict the blood pressure (BP) response to spironolactone is not clear. METHODS: We correlated the BP response to spironolactone 50 mg/day to baseline ARR in 69 hypertensive patients (mean [+/-SD] age 57 +/- 2 years, 65% male), consisting of 39 subjects with long-standing hypertension (4.0 +/- 0.2 years) whose hypertension was uncontrolled on at least three antihypertensive medications and 30 previously untreated patients who were randomized in a cross-over design to receive either spironolactone 50 mg/day or bendroflumethiazide 2.5 mg/day for 4 weeks. RESULTS: After 4 weeks of spironolactone, BP in patients with never-treated hypertension was reduced by 18 +/- 3 / 11 +/- 1 mm Hg. There was a highly significant correlation between log ARR and the fall in systolic BP (r = 0.69, P < .001) and diastolic BP (r = 0.45, P < .05). Nine of ten patients with low renin activity (< or =0.5 ng/mL/h) showed a >20-mm Hg fall in systolic BP. No such correlations were seen when BP was reduced by bendroflumethazide 2.5 mg. For patients with resistant hypertension, despite a BP reduction of 28 +/- 3 / 13 +/- 2 mm Hg after 14 weeks of spironolactone, there was no relationship between the reduction in BP and the ARR; however, subjects with pretreatment potassium <4.0 mmol/L had a greater response than those with levels > or =4.0 mmol/L (34 +/- 3 / 16 +/- 2 v 20 +/- 6 / 8 +/- 3 mm Hg, P < .05) CONCLUSIONS: Based on the study results, ARR and low renin activity may predict the response to spironolactone in never-treated hypertensive patients but not in patients taking antihypertensive drugs, possibly because of the effect of these agents on ARR. In such patients a trial of spironolactone is required to assess the BP response.

Aldosterone-to-renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension.

BACKGROUND: Some 10% to 15% of hypertensive patients have hyperaldosteronism, an increased ambulant aldosterone-to-renin ratio. As aldosterone reduces arterial compliance, we examined the relationship between aldosterone-to-renin ratio, aortic blood pressure (BP), arterial stiffness, and the effect of spironolactone in a hypertensive population. METHODS: In 24 untreated patients (mean age 51 +/- 2 years, 10 women), we assessed arterial stiffness by augmentation index-height of the late systolic peak in the aorta, pulse pressure (Sphygmocor), and aortic pulse wave velocity (Complior). RESULTS: There were significant positive correlations between the aldosterone-to-renin ratio and aortic systolic pressure, aortic pulse pressure, and augmentation index and negative correlations with pulse pressure amplification, but none with brachial BP or pulse wave velocity. After randomization in a cross-over design to 50 mg of spironolactone or 2.5 mg of bendroflumetazide for 4 weeks with washout period of 1 month, both drugs significantly reduced brachial BP, but only spironolactone reduced (P < .001) pulse wave velocity and augmentation index, which remained significant when corrected for its greater reduction in mean BP. There were significant (P < .001) positive correlations between the ratio and decrease in aortic systolic (r = 0.78), mean (r = 0.75), diastolic BP (r = 0.66), aortic pulse pressure (r = 0.69, augmentation index (r = 0.64) and with, brachial systolic pressure (r = 0.66), brachial pulse pressure (r = 0.44, P < .05) and pulse pressure amplification (r = 0.46, P < .05). Such relationships were not found with pulse wave velocity. CONCLUSIONS: The aldosterone-to-renin ratio may have an important role in determining arterial stiffness, particularly wave reflection and aortic systolic pressure and is of predictive value for the responsiveness to spironolactone. Aldosterone antagonism has BP-independent effects on arterial stiffness.

Differential cognitive outcomes in the Hypertensive Old People in Edinburgh study.

Hypertension is associated with cognitive impairment in older adults. The Hypertensive Old People in Edinburgh (HOPE) study reported improved scores in two psychometric tests in those subjects with the greatest fall in diastolic blood pressure during a 24-week randomised, double-blind trial of captopril versus bendrofluazide in 81 elderly hypertensive people with mild cognitive impairment. Three hundred and eighty-seven of the original sample of 603 older people with and without hypertension and/or cognitive impairment from which the trial subsample was drawn were available for adequate psychometric testing 4 years later. Blood pressure was related prospectively to Raven's Progressive Matrices (RPM), a measure of fluid intelligence, but not memory differences. RPM scores were obtained at baseline, 6 weeks, 12 weeks and at the end of the randomised controlled trial. For subjects on captopril mean scores at each time point adjusted for blood pressure change were 27.6 (95% CI 25.5-29.6), 27.2 (95% CI 25.1-29.2), 28.4 (95% CI 26.6-30.3) and 28.9 (95% CI 26.9-30.9), and for bendrofluazide 27.1 (95% CI 25.1-29.0), 28.9 (95% CI 26.9-30.9), 28.9 (95% CI 27.2-30.7) and 28.7 (95% CI 26.8-30.6). There was a significant improvement in scores for those on bendrofluazide compared with captopril at week 6 (F=8.10, p=0.006, partial eta2=0.11). There were no significant effects for either drug or blood pressure at any time point for tests of memory. Future trials of the effects of antihypertensive therapy on cognition should focus more on outcomes other than memory. Early differential effects of therapeutic agents may not be maintained.

Doxazosin versus bendrofluazide: a comparison of the metabolic effects in British South Asians with hypertension.

BACKGROUND: People from British South Asian communities have an increased risk of mortality from coronary heart disease (CHD). Doxazosin, a selective alpha(1)-adrenergic blocker, in addition to lowering blood pressure, has been shown to have positive effects on glucose metabolism and lipid profiles in patients with hypertension. AIM: We studied doxazosin (1-8 mg) and bendrofluazide (2.5 mg) in patients of British South Asian origin with existing mild to moderate hypertension (doxazosin n = 78; bendrofluazide n = 82), to compare their effects on glucose and lipid metabolism in this group. DESIGN OF STUDY: A 34-week randomised, double-blind, parallel-group, multicentre study. SETTING: Primary care in the UK. METHOD: All doxazosin patients started with an initial dose of 1 mg once daily, titrated to a maximum 8 mg once daily if diastolic blood pressure was >90 mmHg or was not <5 mmHg of the baseline value. The primary efficacy variables were mean glucose and total cholesterol concentrations at week 21. RESULT: Doxazosin reduced glucose, total cholesterol, low-density lipoprotein-cholesterol and triglycerides and increased high-density lipoprotein-cholesterol. There were significant differences between doxazosin and bendrofluazide for glucose concentrations at week 21 (P = 0.029) and week 34 (P = 0.015), total cholesterol at week 21 (P = 0.048) and triglycerides at week 21 (P = 0.047) and week 34 (P = 0.009). There was no significant difference in blood pressure lowering between the two treatments. CONCLUSION: Doxazosin exhibits beneficial effects on glucose concentrations and lipid profile, in particular in lowering triglyceride concentrations in British South Asians. Whether these desirable characteristics translate to improved overall cardiovascular risk requires formal evaluation.

Triiodothyronine-induced thyrotoxicosis in ophthalmic Graves disease.

A euthyroid woman with ophthalmic Graves disease developed endogenous hyperthyroidism coincident with T3 suppression test. There is a putative role of liothyronine administration in precipitating or activating hyperthyroidism. Aberrancies in T3 suppression testing in graves disease occur.

Cigarette smoking interferes with treatment of hypertension.

We retrospectively analyzed two studies to determine whether smoking affected the treatment of hypertension. In a study of the effects of propranolol hydrochloride (a hepatically metabolized beta-blocker) vs hydrochlorothiazide, 108 smokers and 232 nonsmokers were randomized to the propranolol treatment group. The propranolol-treated smokers tended to be younger, taller, thinner, and wre more likely to be black. This group also had an initial blood pressure reduction (+/- SD) of -7.9 +/- 12.9/-8.7 +/- 8.4 mm Hg compared with -10.7 +/- 13.0/-10.9 +/- 7.1 mm Hg for the nonsmokers. Blood pressure increased less during the one-year maintenance period for the nonsmokers. However, when analyzed by race, this effect was seen in blacks, but not in whites. Diastolic blood pressure tended to be reduced more in nonsmokers (vs smokers) receiving hydrochlorothiazide (-12.1 +/- 6.7 vs -10.7 +/- 6.7 mm Hg, respectively). The second study compared the effects of nadolol (a renally excreted beta-blocker) with bendroflumethiazide. There were no significant effects on blood pressure for either of these drugs. In both studies, there was a greater tendency for smokers to be terminated from the study irrespective of drug group. We conclude that cigarette smoking does interfere with the treatment of hypertension in general, and especially with reduction of blood pressure by propranolol in black patients.

[Old or new antihypertensives--which are better?]. / Differenzialtherapie mit alten und neuen Antihypertensiva. In der Praxis brauchen Sie alle fünf.

Some of the reported findings of numerous studies on the treatment of hypertension are still giving rise to heated discussions. The result is conflicting recommendations and uncertainty among care-providing physicians. Today, the substances from the group of more recent hypertensive agents (calcium antagonists, ACE-inhibitors and angiotensin 1 receptor blockers) together with the classical agents (diuretics and beta blockers) are recognized as equally justifiable as the five agents of first choice in the treatment of uncomplicated hypertension. If, however, accompanying diseases are present, the choice of primary medication depends on the respective risk (diabetes, etc.) of the individual patient. In many cases, combination treatment should be considered from the very beginning.

A diuretic is more effective than a beta-blocker in hypertensive patients not controlled on amlodipine and lisinopril.

The combination of an angiotensin-converting enzyme inhibitor and a calcium antagonist has a synergistic effect in patients with more severe hypertension. However, when this combination fails to control blood pressure, it is not clear which drug is then additive. The aim of this work was to study in a double-blind, randomized, crossover design the effect on blood pressure of the addition of either a thiazide diuretic (bendrofluazide, 5 mg once daily) or a beta-blocker (atenolol, 100 mg once daily) or placebo each for a month in hypertensive patients who are not adequately controlled on the combined treatment of amlodipine 5 mg once daily and lisinopril 5 mg twice daily. Eighteen patients with a supine diastolic pressure of more than 90 mm Hg after at least 1 month on the combined treatment of amlodipine and lisinopril were enrolled in the study. The results show that in patients whose blood pressures are not controlled by the combination of amlodipine and lisinopril, the addition of bendrofluazide 5 mg once daily causes a significant fall in blood pressure compared with placebo and a significantly greater fall than 100 mg atenolol once daily.

Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations.

A double-blind crossover comparison was made in 18 nonedematous hypertensive subjects with glomerular filtration rates exceeding 70 ml/min/1.73 m2 of the effects of 5 mg metolazone and 5 mg bendroflumethiazide on blood pressure and metabolic parameters. After a 4-wk run-in placebo period, patients received either metolazone or bendroflumethiazide for 6 wk in a crossover fashion with an intervening washout period of 4 wk. Metolazone induced a more sustained and greater blood pressure response than bendroflumethiazide. Changes in plasma potassium, urate, bicarbonate, renin, and angiotensin II occurred during treatment with both metolazone and bendroflumethiazide; the only significant difference, however, was in changes in plasma bicarbonate. Total body potassium (TBK), measured by whole-body monitor, did not fall outside the normal range with either metolazone or bendroflumethiazide, although metolazone induced a greater reduction in TBK (6.2 gm, 5.5% of TBK) than bendroflumethiazide (1.2 gm, 1.1% of TBK, p < 0.05). Our results suggest that metolazone is a more effective antihypertensive and induces similar but greater metabolic changes than bendroflumethiazide. The results of our comparison suggest that although changes in plasma potassium and TBK are minor, they are greater with metolazone, and potassium supplements may not be necessary in nonedematous hypertensive patients with normal renal function.