Prof. Gregory Y. H. Lip
There is a dose-response relationship between an increasing blood pressure and an increasing risk of stroke and coronary heart disease . The treatment of hypertension results in a 30-35% reduction in strokes and a 20% reduction in heart attacks . It is therefore crucial to detect, treat and control high blood pressure, and if management of hypertension is inadequate or inappropriate this could even be considered as negligent. It is no longer a question of ‘do we treat’ hypertension, but more a question of ‘who to treat’ and ‘how to treat’ hypertension.
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.
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 .
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.
MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, et al. Blood pressure stroke and coronary heart disease: part I, prolonged differences in blood pressure: prospective observational studies corrected for regression dilution bias. Lancet 1990; 335: 765-74 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1969518&dopt=Abstract
Collins R, Peto R, MacMahon S. Herbert P, Fiebach NH, Kimberley AE, Godwin J, et al. Blood pressure stroke and coronary heart disease: part 2 short term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335 827-38 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1969567&dopt=Abstract
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. JAMA 2003; 289: 2560-72 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12748199&dopt=Abstract
Ramsey LE, Williams B, Johnston GD, MacGregor GA, Poston L, Poulter NR, Russell G. Guidelines for Management of hypertension: report of the third working party of the British Hypertension Society. J Hum Hypertens 1999;13:569-592 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10482967&dopt=Abstract
Beevers DG. Beta-blockers for hypertension: time to call a halt. J Hum Hypertens. 1998 ;12(12):807-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9883700&dopt=Abstract
Grossman E, Messerli FH. Why beta-blockers are not cardioprotective in elderly patients with hypertension. Curr Cardiol Rep. 2002;4(6):468-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12379165&dopt=Abstract
Beevers DG, Ferner RE. Why are thiazide diuretics declining in popularity? J.Hum.Hypertens. 2001;15:287-289.
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288:2981-2997. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12479763&dopt=Abstract
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group. JAMA 2000; 283:1967-1975. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10789664&dopt=Abstract
Beevers DG, Lee KW, Lip GY. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): ALL predictable and no big surprise out of a HAT? J Hum Hypertens. 2003 Jun; 17(6):367-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12764397&dopt=Abstract
McInnes GT. ALLHAT: a saga of missed opportunities. J Hum Hypertens. 2003; 17(6):373-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12764398&dopt=Abstract
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360:7-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12114036&dopt=Abstract
Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12686036&dopt=Abstract
Nadar S, Lim HS, Beevers DG, Lip GY. Lipid lowering in hypertension and heart protection: observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and the Heart ProtectionStudy. J Hum Hypertens. 2002;16(12):815-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12522461&dopt=Abstract
Lip GYH, Beevers M, Beevers DG. The 'Birmingham Hypertension Square' for the optimum choice of add-in drugs in the management of resistant hypertension. J Hum Hypertens 1998; 12:761-763. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9844947&dopt=Abstract
Gregory Y. H. Lip MD F.E.S.C. , Professor of Cardiovascular Medicine Nucleus member of the Working Group on Hypertension and the Heart University Department of Medicine City Hospital Birmingham B18 7QH England, UK Tel: +44 121 5075080; Fax: +44 121 554 4083; firstname.lastname@example.org www.swbh.nhs.uk/teaching
Our mission: To reduce the burden of cardiovascular disease
© 2017 European Society of Cardiology. All rights reserved