B Neal

1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization.

The present Guidelines were prepared by the Guidelines Sub-Committee of the World Health Organization-International Society of Hypertension (WHO-ISH) Mild Hypertension Liaison Committee, the members of which are listed at the end of the text. These guidelines represent the fourth revision of the WHO-ISH Guidelines and were finalised after presentation and discussion at the 7th WHO-ISH Meeting on Hypertension, Fukuoka, Japan, 29th Sept-1st Oct, 1998. Previous versions of the Guidelines were published in Bull WHO 1993, 71:503-517 and J Hypertens 1993, 11:905-918.

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk

Background There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol (‘polypills’) to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. Methods We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. Findings At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. Conclusions This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12607000099426

Blood Pressure Lowering for the Secondary Prevention of Myocardial Infarction and Stroke

Blood pressure (BP) levels are directly and continuously associated with the risks of both coronary heart disease and stroke in individuals without a history of major cardiovascular disease,1 and randomized trials in patients with hypertension have demonstrated that BP lowering reduces these risks after just a few years of beginning treatment.2 3 The proportional benefits of treatment appear to be similar in higher and lower risk patients, and the absolute benefits therefore increase with the level of absolute risk.3 This raises the possibility that patients at highest absolute risk of myocardial infarction or stroke, namely, those with established coronary or cerebrovascular disease, stand to benefit most from BP lowering. However, questions about the safety of BP reduction for patients with preexisting cardiovascular disease have been raised following observations of J- and U-shaped associations between BP levels and the risks of recurrent myocardial infarction4 and stroke.5 Until recently, it has been unclear whether the J- and U-shaped associations resulted from low BP causing an increase in recurrent events or from more severe or unstable disease causing a decrease in BP and, independently, an increased risk of recurrence. If the latter were true, it could be hypothesized that the nonlinear associations would be most marked in the first few years of follow-up, when …

The Progress study: rationale and design

Rationale : Patients with a history of cerebrovascular disease have a very high risk of stroke, and usual levels of both systolic and diastolic blood pressure are directly and continuously associated with this risk. Trials of blood pressure lowering in patients with transient ischaemic attacks or stroke have been too small to reliably detect the effects on stroke risk of the modest blood pressure reductions achieved. Objectives : The primary objective of PROGRESS is to determine precisely the effects of blood pressure reduction with an angiotensin converting enzyme (ACE) inhibitor-based regimen on the stroke risk in patients with a history of transient ischaemic attacks or minor stroke. Design : The study is a randomized, double-blind, placebo-controlled clinical trial. Before randomization, there is a 4-week run-in phase on open-label ACE inhibitor treatment. The scheduled duration of treatment and follow-up is 4-5 years. Setting : The study will be conducted in collaborating clinical centres in Australia, Belgium, the Peoples Republic of China, France, Italy, Japan, New Zealand, Sweden and the United Kingdom. Patients : The study will involve 6000 patients with a history of transient ischaemic attacks or stroke (ischaemic or haemorrhagic) in the past 5 years. To be eligible patients should have no definite indication for or contra-indication to treatment with an ACE inhibitor and no disability likely to prevent regular attendance at study clinics. Interventions : Study treatment will comprise perindopril and indapamide or matching placebos for patients without an indication for or contra-indication to treatment with a diuretic, perindopril alone or matching placebo for all other patients. Study outcomes : The primary study outcome is total strokes and secondary outcomes include fatal or disabling strokes, total major cardiovascular events, cardiovascular deaths, cognitive function and dementia, and disability and dependency.

Blood pressure lowering in patients with cerebrovascular disease: results of the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) pilot phase.

1. Among patients with cerebrovascular disease, there is a direct and continuous association between blood pressure and the risk of stroke, but previous trials of blood pressure lowering in this patient group have been inconclusive.

An Overview of 37 Randomised Trials of Blood Pressure Lowering Agents Among 270,000 Individuals

Overviews (meta-analyses) of the major ongoing randomized trials of blood pressure lowering drugs will be conducted to determine the effects of: first, newer versus older classes of blood pressure lowering drugs in patients with hypertension; and second, blood pressure lowering treatments versus untreated or less treated control conditions in patient groups at high risk of cardiovascular events. The principal study outcomes are stroke, coronary heart disease, total cardiovascular events and total cardiovascular deaths. The overviews have been prospectively designed and will be conducted on individual patient data. The analyses will be conducted as a collaboration between the principal investigators of participating trials involving about 270,000 patients. Full data should be available in 2003, with the first round of analyses performed in 1999-2000. The combination of trial results should provide good statistical power to detect even modest differences between the effects on the main study outcomes.

Blood Pressure Lowering for the Prevention of Cognitive Decline in Patients with Cerebrovascular Disease

Cerebrovascular disease and high blood pressure both appear to increase the risk of vascular dementia. PROGRESS aims to investigate whether blood pressure lowering with an angiotensin converting enzyme inhibitor-based regimen will reduce the risk of cognitive impairment in patients with a history of stroke or transient ischaemic attack. A total of at least 6000 patients will be randomised to receive perindopril (± indapamide) or matching placebo(s), with treatment and follow-up scheduled to continue for at least 4 years. Substudies will investigate the effects of treatment on cognitive decline in subgroups defined by apo-E genotype and on white matter lesions assessed by magnetic resonance imaging. Final results from the study should be available in 2001.