Who to treat?
Hypertension can be defined pragmatically as that level of blood pressure above which the use of antihypertensive treatment does more good than harm. Indeed, hypertensive patients do not make up a homogeneous population and hypertension per se is not a condition that can be regarded in isolation. All major hypertension management guidelines recommend the use of risk stratification, in the context of a patient’s total cardiovascular risk , . Indeed, risk factors such as diabetes mellitus, hyperlipidaemia, smoking, age and gender need to be taken into account, as these risk factors are cumulative to the overall cardiovascular risk burden. All risk factors must therefore be managed in a holistic manner, in a ‘package of care’ that includes treating high risk groups, with non-pharmacological and pharmacological measures.
How to treat?
Until recently, the thiazide diuretics and beta-blockers have been regarded as the mainstay of hypertension treatment. However, there is an increasing recognition that beta-blockers are ineffective as first-line agents in the elderly and in Afro-Caribbean patients - whether beta-blockers are even effective in reducing endpoints in hypertension, especially in the elderly has been extensively debated , . On the other hand, thiazides are cheap and effective agents, but the lowest possible dose should be used, as there is no dose-response antihypertensive effect, whilst higher doses of thiazides are associated with increasing metabolic effects .
Many randomised controlled trials have also compared the newer antihypertensive agents, such as the alpha blockers, calcium antagonists, ACE inhibitors and angiotensin receptor antagonists to the ‘old’ drugs, thiazides and beta-blockers. The largest was the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in ‘high-risk’ hypertensive patients who were initially randomised to a diuretic (chlorthalidone) versus each of three ‘alternative’ (newer) antihypertensive drugs: an alpha-adrenergic blocker (doxazosin), an ACE-inhibitor (lisinopril), and a CCB (amlodipine) . The doxazosin arm was stopped early due to an excess of cardiovascular events, especially heart failure. For the thiazide, ACE inhibitor, and dihydropyridine calcium antagonist arms of the study, the incidence of the primary endpoints of fatal coronary heart disease (CHD) and non-fatal myocardial infarction (MI), was essentially identical, although there was an apparent excess of stroke endpoints in the lisinopril arm, and more heart failure with lisinopril and amlodipine compared to thiazide. The merits (or otherwise!) of the ALLHAT trial have recently been extensively discussed.
Recent recognition of the value of lipid lowering therapy in hypertension is provided by the MRC/BHF Heart Protection Study (HPS) , which studied patients at ‘high risk’ of death due to coronary heart disease (41% were hypertensive), where the use of simvastatin 40mg/day reduced all cause mortality (12.9% versus placebo, 14.7%). There were also significant decreases in non fatal myocardial infarctions, fatal or non fatal strokes and coronary or non coronary revascularisations. These data from the HPS were complemented by the lipid-lowering arm data from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) study . In the latter, atorvastatin 10mg daily was associated with a significant reduction in the primary end point of fatal myocardial infarction and nonfatal coronary heart disease events (by 36%), together with significant reductions in the secondary end points of stroke (by 27%), all cardiovascular events and procedures (by 21%), and total coronary events (by 29%). Risk reductions in CHD events in both HPS and ASCOT were unrelated to baseline cholesterol levels and were consistent across the whole range of cholesterol. The merits and issues with regard to using lipid lowering in hypertension have recently been discussed .
Implications for management
The recent trials have proven the value of a holistic approach to cardiovascular risk management in hypertensive patients with additional risk factors, by the addition of statin therapy, irrespective of serum cholesterol level. It is clear that we have to move away from treating individual risk factors such as hypertension or hyperlipidaemia in isolation, and all risk factors need a complete, comprehensive ‘package of care’ of cardiovascular risk management.
The data from ALLHAT also would advise some degree of caution with the use of alpha-blockers in hypertensives at risk of heart failure. Most trials also confirm the need for combination therapy to achieve adequate blood pressure control – generally <140/85mmHg in non-diabetics and <130/80mmHg in diabetes – and as an average, half of all hypertensives will require two or more drugs, whilst a third will require three or more drugs to achieve adequate blood pressure control. It therefore makes sense to use antihypertensive agents that are synergistic in action to each other, as well as minimising adverse effects (if any) from each other. To assist in the rational selection of antihypertensive treatment, the "Birmingham Hypertension Square" can be used for 'add-in' antihypertensive therapy . After choosing a logical first-line drug, the possible second-line agents are immediately adjacent on the square, as indicated by the arrows [Figure 1]. Third-line drugs can be chosen in similar fashion.
The ‘Birmingham Hypertension Square’
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.