In 2004, the British Hypertension Society (BHS) published its fourth guidelines on the management of hypertension.1 For patients who need treatment,most will require combination therapy to reach target blood pressure levels, and the guidelines’ AB/CD algorithm is intended to encourage the use of logical drug combinations.2
Later that year, NICE published its guideline for the management of hypertension in primary care.3 NICE recommended initial therapy with a low-dose thiazide-type diuretic, adding as second-line therapy a beta blocker or, for those at risk of new onset diabetes,an ACE inhibitor or angiotensin receptor blocker. A calcium channel blocker was recommended as third-line therapy. The advice to avoid the diabetogenic combination of thiazide-type diuretic with a beta blocker in at-risk patients was in line with the BHS guidelines.
The systematic review underpinning the NICE guideline demonstrated the benefits of using a low-dose thiazide type diuretic or a beta blocker to prevent stroke or myocardial infarction. The PROGRESS trial provided the evidence for a similar benefit of an ACE inhibitor in stroke patients.4
Doubts about the benefits of the betablocker atenolol were raised in a systematic review published in November 2004.5 Compared with placebo,no outcome differences were seen,apart from a tendency to a lower risk of stroke.However, when compared with other anti-hypertensive agents, atenolol was associated with more strokes and a higher mortality. However, only now, with the publication of the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm (ASCOT-BPLA)6 has the approach recommended by the BHS been tested in a major outcome trial. This trial randomised 19 257 patients aged 40-79 years with hypertension and other risk factors to treatment with amlodipine with perindopril added as required or atenolol plus a thiazide (bendroflumethiazide).
Although the primary endpoint of non-fatal MI and fatal CHD only became significant when coronary revascularisations were included, all other endpoints favoured the newer drugs combination of calcium-channel blocker and ACE inhibitor.
Benefits were seen in all the pre-specified subgroups, including patients with diabetes and others with end-organ damage. Multivariate adjustment of blood pressure and other risk factors accounted for 50% of the differences in coronary events and 40% of the differences in stroke events between the two treatment groups.7 Higher HDL cholesterol may help to account for the coronary benefit not related to blood pressure.
The ASCOT Lipid Lowering Arm (LLA) study published in 2003 has shown the benefits of statin therapy in hypertensive patients.8 When the benefits of a calcium-channel blocker, ACE inhibitor and statin are compared with the most common current blood pressure therapy of a beta-blocker and a thiazide, there is an impressive two-fold benefit in the reduction of both non-fatal MI and fatal CHD and in fatal and non-fatal stroke.
The BHS and NICE guideline development groups plan to meet soon to discuss modifications to current guidance in the light of the ASCOT results.
Doubtless there will be a significant change in the drugs GPs use to treat hypertension and prevent cardiovascular events, involving a shift to the newer regimens of a calcium-channel blocker and ACE inhibitor with a thiazide- type diuretic as step three. Beta blockers will be reserved for patients with established CHD, with specific ones used to treat heart failure.We will also need a new impetus to treat all patients with hypertension, on blood pressure lowering treatment, with a statin, unless contraindicated.
- Williams B, Poulter NR, Brown MJ et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004- BHS IV. J Hum Hypertens 2004; 18: 139-85.
- Brown MJ, Cruickshank JK, Dominiczak AF et al; Executive Committee, British Hypertension Society. Better blood pressure control: how to combine drugs. J Hum Hypertens 2003; 17: 81-6.
- National Institute for Clinical Excellence. Hypertension – management of hypertension in adults in primary care. London: NICE, 2004.
- PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attacks. Lancet 2001; 358: 1033-41.
- Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension:is it a wise choice? Lancet 2004;364:1684-89.
- Dahlof B, Sever PS, Poulter NR et al; ASCOT investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required,in the Anglo-Scandinavian Cardiac Outcomes Trial- Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005; online.
- Poulter NR, Wedel H, Dahlof B et al. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo- Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet 2005; online.
- Sever PS, Dahlof B, Poulter NR et al; ASCOT investigators. 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: 1149-58.