Microalbuminuria in subjects with hypertension attending specialist blood pressure clinics.

Albuminuria is associated with increased risk of cardiovascular disease and target organ damage in patients with diabetes mellitus. In nondiabetic hypertensive patients, the threshold at which microalbuminuria (MAU) increases risk is unclear and there is evidence that cardiovascular risk may be increased in individuals with MAU levels lower than the usual recommended screening thresholds. We compared two definitions of MAU (on the basis of three early morning urine samples) in a cohort of hypertensive patients attending two specialist clinics in Scotland: conventional (MAU(C)) albumin-to-creatinine ratio (ACR) >2.5-25 mg mmol(-1) in males or >3.5-25 mg mmol(-1) in females; and low-grade (MAU(L)) ACR 1.2-2.5 in males or 1.7-3.5 mg mmol(-1) in females. Of the 1059 subjects screened, 786 (74%) were nondiabetic, with estimated glomerular filtration rate ⩾30 ml min(-1) per 1.73 m(2) and without gross proteinuria (low-risk subset). The average age was 58±15 years, body mass index 30±6 kg m(-2) and 46% were males. The prevalence of MAU(C) was 11% and 9.5% in the overall and low-risk subset, respectively, whereas MAU(L) prevalence was 11.1% and 10% respectively. The prevalence of cardiovascular disease was higher (24%) with albuminuria (both MAU(C) and MAU(L)) compared with 14% among those without albuminuria. The use of MAU(L) doubled the number of hypertensive subjects with increased cardiovascular risk who can be targeted for more rigorous risk reduction strategies. Consideration should be given to reducing the current threshold for MAU.

Angiotensin-II receptor blockers: benefits beyond blood pressure reduction?

Effective treatment of hypertension is essential to reduce the risk of renal and cardiovascular (CV) morbidity. The risks associated with hypertension are modulated by the presence of other factors. This has prompted the quest for agents that have benefits beyond blood pressure (BP) lowering. The angiotensin II receptor blocker (ARB) class of antihypertensive agents represents an important addition to the therapeutic options for elevated BP. Their ability to control BP is equivalent to existing therapies and there is a considerable and mounting evidence-base for their ability to reduce hypertension-associated target organ damage and comorbidities. Studies show that ARBs have clinical benefits across the spectrum of disease severity. In particular, recent large studies have demonstrated that these benefits extend to patients with conditions predisposing to CV events, such as diabetes, left ventricular hypertrophy and microalbuminuria, and where risk factors coexist. Data from these studies suggest that the CV protective effects of ARBs are at least, in part, independent from the BP lowering action. In addition, ARBs are extremely well tolerated, and strong evidence suggests that compliance with therapy--a key factor in achieving adequate BP control--with ARBs is higher than with other antihypertensive agents. Furthermore, flexible dosing and good tolerability profile mean that, where necessary, ARBs can be combined with other classes of antihypertensive agents to achieve adequate BP control and reduce the risk of hypertension-associated morbidity.

Relative potency of amiloride and spironolactone in healthy man.

The renal antimineralocorticoid activity of single oral doses of amiloride, a physiologic aldosterone antagonist, was compared to that of spironolactone, a competitive aldosterone antagonist, in 12 healthy men pretreated with fludrocortisone. For up to 20 hr amiloride induced linear log dose-urinary electrolyte response relationships but spironolactone dose-response trends were demonstrated only in the period from 10 to 20 hr after treatment. In this period, the best estimate of the potency of amiloride relative to spironolactone for urine log10 10 Na/K was 36 (95% confidence limits 23 to 69). The fludrocortisone model seems appropriate for quantitative comparisons of physiologic and competitive aldosterone antagonists, but does not indicate therapeutic relative potency.

Dose-response relationships for spironolactone in combination with a potassium-wasting diuretic.

The plasma and urine electrolyte responses to repeated doses of spironolactone, 25, 50, and 100 mg, in combination with metolazone, 2.5, 5.0, and 10 mg, were examined in 18 healthy subjects (six at each dose of metolazone). During the period of pharmacologic steady state, there were log linear spironolactone dose-response relationships for plasma potassium, sodium, and bicarbonate (P less than 0.001 in each case) with no contraindication to parallelism between the metolazone groups. In the absence of mineralocorticoid challenge, spironolactone dose-urine electrolyte responses could not be demonstrated. However, after fludrocortisone, spironolactone log dose-response trends were linear with respect to natriuresis (P = 0.027), antikaliuresis (P = 0.020), and log 10 Na/K (P = 0.001), which is usually considered the best single index of renal antimineralocorticoid activity, and exhibited parallelism between the metolazone doses. These observations suggest that a convenient bioassay for aldosterone antagonists in normal men may be provided by the electrolyte responses to repeated doses of such drugs in combination with potassium-wasting diuretics. In view of the limitations of other methods, this approach may have particular relevance to the evaluation of potassium-sparing properties.

Steady-state relative potency of aldosterone antagonists: spironolactone and prorenoate.

The dose ratio approach was used to define the steady-state relative potency of the competitive mineralocorticoid antagonists prorenoate potassium and spironolactone in six healthy male subjects using fludrocortisone as mineralocorticoid agonist. Log fludrocortisone dose-response relationships in the presence or absence of antagonists did not differ from linearity and parallelism, supporting the theoretical basis of the method. Urinary sodium and plasma potassium responses appeared to behave according to the law of mass action, which made possible estimation of the potency of prorenoate relative to spironolactone on a weight basis-4.2:1 (95% C.L. 2.7-6.9:1) and 2.68:1 (95% C.L. 0.71-6.57:1, respectively. The steady-state relative potency for sodium excretion was greater than previously estimated after single doses. Mass action theory could not explain the urinary potassium and log 10 Na/K responses to repeated doses of spironolactone, precluding valid estimation of relative potency for these variables and suggesting that the latter response alone is an unreliable index of overall renal antimineralocorticoid activity.

Dose-response relationships for spironolactone at steady state.

The overnight urine electrolyte and plasma potassium responses to spironolactone (25, 50, 100, and 200 mg daily) at steady state were investigated in 11 healthy subjects after fludrocortisone challenge. For sodium excretion and urine log10 10 Na/K, log dose-response relationships were defined (P less than 0.001 in each case), but there was little evidence of dose-related influences on potassium excretion or plasma potassium. The findings confirm the limitations of the fludrocortisone model in evaluating the potassium-sparing properties of aldosterone antagonists at steady state and of the urine sodium; potassium ratio as an overall index of renal antimineralocorticoid activity.

Activity of sulfur-containing intermediate metabolites of spironolactone.

The renal antimineralocorticoid activity of single administration of 2 sulfur-containing compounds, which are thought to be intermediate metabolites of spironolactone, was assessed in healthy subjects. They were each active in reversing the urinary electrolyte changes indiced by fludrocortisone for 2 to 10 hr after dosing, but only the 7 alpha-thiomethyl derivative exhibited activity in the period 12 to 16 hr after treatment. The activity of both drugs was less than of spironolactone. Taking urinary log 10 Na/K as the best index of antimineralocorticoid activity, the potencies of the intermediates relative to spironolactone were 0.26 (95% confidence limits, 0.12 to 0.49) for 7 alpha-thio-spirolactone and 0.33 (95% confidence limits, 0.15 to 0.62) for 7 alpha-thiomethyl-spirolactone in the period 2 to 10 hr after medication. We conclude that these minor sulfur-containing intermediate metabolites of spironolactone are unlikely to contribute significantly to the renal antimineralocorticoid activity of spironolactone.

Bioassay of a new aldosterone antagonist and evaluation of a simple method of quantitative comparison.

The renal antimineralocorticoid activity of single oral doses of a new aldosterone antagonist OH OPC(ME)-K was compared to that of spironolactone in two studies in healthy men. OH OPC(ME)-K reversed the urinary electrolyte response to fludrocortisone in the period up to 16 hr after treatment, but it was less potent than spironolactone on a weight basis. The best estimate of the relative potency of OH OPC(ME)-K: spironolactone (derived from a simple protocol using equal single doses of the two drugs) was 0.60:1 (95% confidence limits 0.24:1 to 1.42:1), in good agreement with the estimate from a more complex three-dose parallel-line bioassay (0.61:1, 95% confidence limits 0.48:1 to 0.79:1). The results of simple single-dose studies can be used, with certain assumptions, to provide a useful estimate of the relative potency of new aldosterone antagonists at an early stage of development.

Comparison of lipid-lowering effects of low-dose fluvastatin and conventional-dose gemfibrozil in patients with primary hypercholesterolemia.

A total of 123 patients with primary hypercholesterolemia were randomized on a 2:1 ratio to receive either fluvastatin at 20 mg once daily at night (n = 82) or gemfibrozil at 600 mg twice daily (n = 41) in a double-blind, double-dummy comparison of the effects on plasma lipid parameters and tolerability over 8 weeks. All patients had either low-density lipoprotein cholesterol (LDL-C) concentrations > or = 160 mg/dL (4.1 mmol/L) in association with definite coronary artery disease (CAD) or > or = 2 risk factors, or LDL-C > or = 190 mg/dL (4.9 mmol/L) with no CAD and < 2 risk factors. All had triglyceride (TG) levels < or = 350 mg/dL (4.0 mmol/L). After 8 weeks of treatment, fluvastatin produced significant reductions from baseline of 17.4% (p < 0.001) in LDL-C, 13.2% (p < 0.001) in total cholesterol (TC), 13.8% (p < 0.001) in very low-density lipoprotein cholesterol (VLDL-C), and 6.4% (NS) in TG. High-density lipoprotein cholesterol (HDL-C) was increased by 5.6% (p < 0.001), and the ratio of LDL-C:HDL-C (Friedewald) was decreased by 21.2% (p < 0.001). Gemfibrozil reduced LDL-C by 15.8%, TC by 13.4%, VLDL-C by 32.2%, LDL-C:HDL-C by 24.8%, and TG by 34.2%, and increased HDL-C by 13.9% (all changes were statistically significant, p < 0.001) compared with baseline. Gemfibrozil produced significantly greater changes in VLDL-C (p < 0.01), HDL-C (p < 0.001), and TG (p < 0.001), but not in LDL-C: HDL-C, compared with fluvastatin. Both drugs significantly reduced apolipoprotein (apo) B and lipoparticles (Lp) E:B, and increased apo A-I but had divergent effects on LpA-I (increased with fluvastatin and reduced with gemfibrozil; p < 0.05). At the end of the study, 43.8% of fluvastatin patients and 45% of gemfibrozil patients achieved a reduction of > 20% in LDL-C levels. Normalization of LDL-C levels was achieved (according to European Atherosclerosis Society guidelines) by 13.4% of fluvastatin- and 14.6% of gemfibrozil-treated patients. Both drugs were well tolerated; adverse events occurred in 36.6% of fluvastatin recipients compared with 58.5% of patients taking gemfibrozil. No clinically notable elevations of aspartate or alanine aminotransferases, alkaline phosphatase, or creatine phosphokinase occurred. No patient developed new or worsening lens opacities associated with a reduction in optically corrected visual acuity. The most commonly reported adverse events were headache and gastrointestinal upset. There were no serious drug-related adverse events.

Compliance with aspirin or placebo in the Hypertension Optimal Treatment (HOT) study.

OBJECTIVE: The Hypertension Optimal Treatment (HOT) study is a large, prospective trial aimed at defining the level of diastolic blood pressure required during anti-hypertensive therapy in order to achieve maximal protection against cardiovascular complications. A further aim is to assess the effects on morbidity and mortality of a 75 mg daily dose of aspirin compared with placebo. SUBJECTS AND METHODS: Compliance with double-blind administration of aspirin or placebo added to anti-hypertensive treatment was evaluated for 1 year in a subset (n = 530) of the study population (n = 18 790) by placing the medication in a container closed with an electronic cap that records precisely the time of each opening. RESULTS: The 1-year compliance rate (percentage of days with one opening per day) could be assessed in 501 patients. It averaged 78.3 +/- 25% in aspirin-treated patients (n = 236, mean +/- SD), compared with 78.5 +/- 25% in patients having received placebo (n = 265), and was not influenced by age, sex or country (Germany, Italy, Switzerland, UK). The compliance rate was also similar irrespective of whether the patients had reached their target blood pressure, but was significantly better during the first than the second 6-month monitoring period (84.1 +/- 22% versus 72.3 +/- 32%, n = 501). CONCLUSIONS: The high rate of compliance with aspirin or placebo observed in the HOT study suggests that the patients were highly motivated and may account for the unusually good blood pressure control achieved in this trial during long-term anti-hypertensive treatment.

Mechanical stretch increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells.

OBJECTIVE: To determine whether changes in haemodynamic load, simulated in vitro by mechanically stretching cultured vascular smooth muscle cells, could be transduced into biochemical signals similar to those produced by growth factors. DESIGN: A system was developed which was capable of stretching cultured vascular smooth muscle cells from 0 to 20%. The effect of stretching quiescent vascular smooth muscle cells on both c-fos messenger RNA (mRNA) expression and release of total inositol phosphates was determined over a time interval of 0-360 min. METHODS: Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Induction of the proto-oncogene, c-fos, was determined by Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]-inositol phosphates released from prelabelled cells. RESULTS: A 20% fixed stretch resulted in a rapid induction of c-fos mRNA which reached maximal levels by 15 min. The amount of c-fos mRNA detected was dependent on the degree of stretch, with maximum induction obtained for 15 and 20% stretch. The effects of mechanical stretch were also assessed on phosphoinositide turnover by measuring [3H]-inositol phosphates released from prelabelled cells. A 20% fixed stretch of vascular smooth muscle cells for 20 min resulted in a 3.2-fold increase in total [3H]-inositol phosphates released compared with unstretched cells. CONCLUSIONS: Our results show that mechanical stretch increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells in vitro. These observations suggest that mechanical stretch and growth factors share common signal transduction pathways which may be important in the development of vascular hypertrophy.

Candoxatril, a neutral endopeptidase inhibitor: efficacy and tolerability in essential hypertension.

OBJECTIVE: To examine the efficacy and tolerability of the neutral endopeptidase inhibitor, candoxatril (UK 79,300) as monotherapy in essential hypertension. DESIGN: Double-blind, placebo-controlled, parallel-group study of 28 days' duration. SETTING: Three hospital outpatient departments participating in the Glasgow Blood Pressure Clinic (Glasgow, UK). PATIENTS: Forty patients with essential hypertension with diastolic blood pressure 95-114 mmHg after a 2-4 week placebo run-in period. INTERVENTIONS: Twenty-eight days' treatment with candoxatril 200 mg twice daily or matching placebo capsules. MAIN OUTCOME MEASURES: Changes in supine and erect blood pressure, and volunteered side effects during double-blind treatment. RESULTS: When measured at the end of the dose interval, the fall in supine blood pressure following candoxatril was not significantly greater than that after placebo. Compared with placebo, a significant effect for candoxatril was seen only for systolic blood pressure in the erect posture; the fall in erect diastolic blood pressure attributable to candoxatril was insignificant. Median plasma atrial natriuretic peptide concentration increased in candoxatril-treated patients and decreased in the placebo group. No stimulation of the renin-aldosterone axis was seen. There was a non-significant trend towards greater urinary excretion of cyclic guanosine monophosphate after candoxatril. Mean plasma concentration of candoxatril at (UK 73,967--the active metabolite of candoxatril) reached a peak of 1010 +/- 437 ng/ml after acute dosing, and 1328 +/- 405 ng/ml after chronic dosing; time to maximum concentration was 2 h in each case. Candoxatril was well-tolerated; numbers of adverse events did not differ between active treatment and placebo. CONCLUSIONS: Although atrial natriuretic peptide levels were significantly increased, candoxatril 200 mg twice daily for 28 days did not produce a clinically relevant fall in blood pressure. Our results cast some doubt upon the role of neutral endopeptidase inhibition in the treatment of unselected hypertensive patients.

Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study. HOT Study Group.

BACKGROUND: The Hypertension Optimal Treatment (HOT) Study has provided information about cardiovascular events in 18790 hypertensives, subjected to pronounced blood pressure (BP) lowering for a mean of 3.8 years. The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk, and it has been found that, despite intensive blood pressure lowering in all risk strata, morbid event rates increased with increasing risk stratum. OBJECTIVES: Previously analysed global risk strata were based on combinations of risk factors. The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk, despite good BP control. METHODS: Risk ratios (RR) for patients with and those without a risk factor were calculated with 95% confidence intervals (CI) using a Cox proportional hazard model, and adjusted for all variables except the one under examination. RESULTS: For all risk factors considered and for all types of event, RR were always greater than 1, indicating a greater risk in the presence, compared with that in the absence of each factor. The male gender was a statistically significant risk for cardiovascular (CV) events, CV and total mortality and particularly for myocardial infarction (MI); age > or = 65 years for CV events, stroke, CV and particularly total mortality; smoking for all events analysed, but particularly for total mortality (twice higher in smokers than in non-smokers); high serum cholesterol (> 6.8 mmol/l) for CV events, MI and CV mortality; high serum creatinine (> 155 micromol/l) for CV events, stroke, CV and total mortality; diabetes for CV events, stroke, total mortality and particularly CV mortality; and ischaemic heart disease for all events analysed. Adjusted RR were often close to or greater than 2. CONCLUSIONS: Each of the risk factors considered was found to be an important cause of residual risk, despite good BP control. These findings emphasize the importance of addressing other correctable risk factors, e.g. smoking, hypercholesterolaemia and diabetes, as well as rigorous control of blood pressure, and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest.

Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.

OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.

Cancer risk of hypertensive patients taking calcium antagonists.

OBJECTIVE: To measure rates of incident and fatal cancer in hypertensive patients taking calcium antagonists and to compare these with rates in three control groups. DESIGN: A retrospective analysis of cancer in patients of the Glasgow Blood Pressure Clinic prescribed either a calcium antagonist or other antihypertensive drugs (non-calcium antagonist group). Record linkage of the clinic with the West of Scotland Cancer Registry and with the Registrar General, Scotland provided information on incidence of cancer and on deaths and their causes. PATIENTS: 2297 patients were prescribed calcium antagonist and 2910 were prescribed antihypertensive drugs other than calcium antagonist. MAIN OUTCOME MEASURES: Relative risk of cancer, the ratio of observed to expected cancers in the calcium antagonist group, was estimated using expected values based on three control groups; namely the non-calcium antagonist group, a middle-aged population of Renfrew and Paisley and the West of Scotland population. RESULTS: There were 134 incident cancers in the calcium antagonist group, representing relative risks of 1.02 [95% confidence interval (CI) 0.82-1.271 compared with the non-calcium antagonist group, 1.01 (95% CI 0.84-1.18) compared with Renfrew-Paisley controls and 1.02 (95% CI 0.85-1.19) compared with West of Scotland controls. Findings for cancer mortality were similarly negative. Risks were no higher for older patients. CONCLUSIONS: Our study lends no support to the suggestion that calcium antagonists cause cancer.

Drug interactions that matter. A critical reappraisal.

Drug interactions are ubiquitous but those with proven clinical relevance are much less common. Only when the combined effects of the interacting drugs are greater or less than the arithmetic sum of their individual actions can the event be considered a true interaction. This eliminates many candidate 'interactions' which in reality merely describe the summation of similar or opposing, but independent, drug effects. An appreciation of those drug interactions that really do matter can be best achieved by combining a practical knowledge of the pharmacological mechanisms involved with awareness of the most vulnerable patients (those with little reserve capacity) and the drugs associated with the greatest risk (those with a narrow therapeutic index). This review follows these guidelines and provides an account of well documented drug interactions categorised according to mechanism.

Effect of micronization on the bioavailability and pharmacologic activity of spironolactone.

The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of these tablets were identical. After 200-mg single doses, the bioavailability of micronized tablets was significantly higher than that of standard tablets. Furthermore, as assessed by 24-hour urine log10 10 Na/K ratio, the pharmacologic activity of micronized spironolactone was significantly greater than that of the standard formulation. The significant influence on renal antimineralocorticoid activity of raised plasma and urinary levels of canrenone, quantitatively the major active metabolite of spironolactone in man, emphasizes the clinical importance of the bioavailability of spironolactone preparations. Since this study, the process used in the manufacture of spironolactone (Aldactone) tablets has been under review.

Delivery of care for hypertension.

To overcome shortcomings in the delivery of care for hypertension various approaches have been developed including a system whereby care of hypertension is shared in a formal manner between general practitioners and hospital specialists. The feasibility, acceptability and cost-effectiveness of a computerised model of shared care were investigated in three matched groups of patients attending hypertension clinics in Glasgow. Glasgow Blood Pressure Clinic attenders considered suitable for shared care by their consultants were randomised to shared care (n = 277) or continued clinic follow-up; a further control group (n = 277) was identified from an independent nurse-practitioner clinic. After 2 years of follow-up, feasibility was estimated by the proportion of patients who had undergone an adequate review (blood pressure, serum creatinine and electrocardiograph); acceptability to general practitioners and patients was assessed by questionnaires; cost-effectiveness was calculated as the cost (to National Health Service and patient) per adequate review. The drop-out rate for shared care over 2 years was 3% compared with 14% for the outpatient clinic and 9% for the nurse-practitioner clinic. In year 2, rates of adequate reviews were 82%, 52% and 75%, respectively. Blood pressure control was similar in the groups. Of 297 general practitioners invited to participate, 85% agreed and 68% wished to continue participation after 2 years. About 50% of shared care patients preferred this method of follow-up compared with their earlier experience of clinic attendance. Shared care was more cost-effective than either conventional or nurse-practitioner clinic follow-up, especially with respect to cost to the patient; costs per adequate review (pound sterling) were 28.96, 50.55 and 30.95, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Why not prescribe the best drugs for hypertension now?

As Westernised societies have become more affluent, the attitudes of the population have become more risk-aware. People are now intolerant of small risks as well as the physical or mental discomforts from drug side effects. Safety and tolerability are now major forces driving the development of new medicines for the treatment of chronic illnesses and the prevention of increasingly rare events. For example, over the past decades, lower and lower treatment thresholds have been recommended in hypertension. Public perception of risk strongly influences the acceptability of lifetime treatment, especially for mild hypertension. This era has also witnessed great advances in the development of antihypertensive drugs that combine efficacy with unsurpassed tolerability. However, the philosophy of Scottish teachers of Materia medica still appears to be followed-'never be the first or the last to prescribe a new drug'. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists are as safe and as efficacious as other antihypertensive medications and better tolerated. Large trials (HOT, HOPE, UKPDS and PROGRESS) point to the need for rigorous control of blood pressure particularly in high-risk individuals. Antihypertensive drugs that act on the renin-angiotensin system will probably impact significantly on achieving optimal blood pressure levels. Should it not now be accepted that high-risk patients should have ACE inhibitors and angiotensin II receptor antagonists prescribed as first-line agents? We review the evidence for the use of ACE inhibitors and angiotensin II receptor antagonists as antihypertensive agents.

Policies for managing hypertensive patients: a survey of the opinions of British specialists.

In September 1988 medically-qualified members of the British Hypertension Society were asked to complete anonymously a questionnaire relating to their views on the management of hypertensive patients. Of 149 questionnaires posted, 90 were returned (60%). There was general agreement that non-pharmacological measures, particularly weight loss and alcohol restriction, are effective treatments. However, there was wide variation in the minimum level of blood pressure considered to warrant drug treatment and little consensus regarding measurement policies or target blood pressures. The drugs of first choice were beta-blockers (54% in men, 35% in women) and thiazide diuretics (28% in men and 47% in women), and they were also the most frequent second choices with 54% of respondents advocating 'stepped-care' based on these drugs. The maximum age at which respondents would be prepared to introduce antihypertensive drugs varied widely although 63% considered that thiazide diuretics are first choice in the elderly. These findings demonstrate a broad range of opinion on the management of hypertension among British specialists, and suggest a continuing need for large clinical trials.