New British-led research shows that starting treatment of blood pressure with two medicines rather than the one produces better and faster results and fewer side effects – findings that could change clinical practice world-wide.
The study, published in the Lancet, challenges popular medical practice for the treatment of high blood pressure. The research was led by Cambridge in collaboration with the Universities of Dundee, Glasgow and the British Hypertension Society.
Doctors usually start treatment with one medicine and then add others over a period of months, if needed, to control blood pressure. This study shows that it is best to start treatment with two medicines together at the same time - resulting in much faster and better control of blood pressure and surprisingly fewer side effects than with one medicine alone.
The two medicines can be incorporated into a single pill, simplifying things for patients who will still only have to take one pill. But by including two medicines in the same pill, they are taking a much more effective medicine with fewer side effects.
Professor Morris Brown, of the University of Cambridge and Addenbrooke's Hospital, said, "The ACCELERATE study breaks the mould for treating hypertension. Most patients can now be prescribed a single combination pill and know that they are optimally protected from strokes and heart attacks."
Prof Bryan Williams, of the British Hypertension Society, said, "This study is important and the findings could change the way we approach the treatment of high blood pressure."
Currently there are almost 10 million people in the UK with high blood pressure and effective treatment is known to substantially reduce the risk of stroke and heart disease.
The investigators believe these important findings could change clinical practice and affect the future treatment of blood pressure for millions of people in the UK.
Professor Tom MacDonald, of the University of Dundee, said: "The research is a great result for patients with high blood pressure. Starting with two medicines is clearly better than starting with one and amazingly there were fewer side effects and not more."
Gordon McInnes, Professor of Clinical Pharmacology at the University of Glasgow, said: "The results of this trial are of huge importance to doctors and people treated for high blood pressure. Future treatment will be more effective and, since fewer side effects will lead to better acceptance of therapy, many fewer heart attacks and strokes are likely."
The 'ACCELERATE' study of 1250 patients with hypertension shows that a new accelerated treatment programme lowers blood pressure faster, more effectively, and with fewer side effects than conventional treatment.
ACCELERATE shows that patients who start treatment with a single tablet containing a combination of drugs will have a 25% better response during the first six months of treatment than patients receiving conventional treatment, and – remarkably – are less likely to stop treatment because of side effects. Still more remarkably, the blood pressure in the conventional treatment arm never caught up with the new treatment arm, even when all the patients in the study were being treated with the same combination of drugs.
The authors suspected that conventional treatment allows the body to partially neutralise each drug, and ACCELERATE was designed to show that the new treatment programme prevents this neutralisation from happening.
ACCELERATE was designed by The British Hypertension Society, who entered a unique partnership with Novartis in order for the treatment programme to be simultaneously tested in ten countries on four continents.
Currently, patients with hypertension take many months to have their blood pressure lowered, following guidance to start with a low-dose of one tablet, and gradually increase the dose and number of drugs. This traditional 'start low, go-slow' policy is encouraged in order to avoid side effects, but has been shown to delay the protection from strokes which is the main reason for treating hypertension. In the longer-term, patients are also less likely to take their medication if multiple tablets are required.
Professor Graham MacGregor, Chairman of UK charity the Blood Pressure Association, said: "High blood pressure is a major cause of stroke and heart disease, so we welcome new research which could lead to improved control of the condition. Many people being treated for high blood pressure need to take more than one medicine, so a combination medicine like this offers the opportunity to take one tablet instead of two, and may be more cost effective for those paying prescription charges."
Funded by the British Heart Foundation, the British Hypertension Society Research Network is now doing a similar study with different medicines to be sure these results are generalisable.
For additional information, please contact:
University of Cambridge Office of Communications:
Tel: +44 (0)1223 766205
Mob: +44 (0)7824 835104
Cambridge University Hospitals NHS Foundation Trust (Addenbrooke's Hospital)
Tel: 01223 274433
University of Dundee
Head of Press
TEL: 01382 384910
University of Glasgow
Media Relations Officer
Tel: 0141 330 3683
British Hypertension Society
British Hypertension Society Administrative Officer
Prof Bryan Williams
On behalf of BHS
Hypertension Research Team
Clinical Sciences Wing
Tel: 07717 467973
Blood Pressure Association,
60 Cranmer Terrace,
Head Office Tel: 020 8772 4994.
Information line: 0845 241 0989. 11am-3pm, Mon-Fri.
Notes to Editors:
1. "Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial" will be published in the Lancet on 13 January.
2. ACCELERATE study details
The ACCELERATE study randomly assigned 1254 patients with a systolic blood pressure greater than 150 mmHg to initial treatment with either aliskiren 150 mg, increasing to 300 mg after 8 weeks, or amlodipine 5 mg increasing to 10 mg after 8 weeks, or the combination of aliskiren 150 mg and amlodipine 5 mg, increasing to twice these doses after 8 weeks. From 16 to 24 weeks, all patients received the same medication, aliskiren 300 mg and amlodipine 10 mg. From 24 to 32 weeks, patients received a third drug, hydrochlorothiazide 12.5 mg, if their blood pressure was greater than 140 mmHg.
The study evaluated two co-primary endpoints: blood pressure over the first 24 weeks, comparing initial combination with the average of initial single therapy; and the blood pressure at 24 weeks, by when all patients were receiving the same treatment. The results show that blood pressure is lowered over a 24 week duration by an additional 6.4/3.7 mmHg in patients started on a combination of aliskiren and amlodipine compared to patients starting with one of the two drugs for sixteen weeks, and then adding the second (p< 0.0001). At 24 weeks and 32 weeks the average blood pressure reductions were numerically greater (~2/1 mmHg, p=0.05), indicating that initial combination therapy does have a lasting influence. By 32 weeks, 62% of patients on the combination reach their blood pressure target (< 140/90 mmHg) versus 53% of patients initiated on amlodipine alone (p=0.02).
The ACCELERATE study also showed no excess adverse effects associated with commencing combination therapy with aliskiren and amlodipine. 13.8% of patients withdrew from initial combination due to side effects, compared to 14.3% from aliskiren and 18.4% from almodipine
3. Why is early blood pressure control important?
Lowering high blood pressure is probably the most evidence-based and cost-effective treatment given to patients. The relationship between high blood pressure and stroke is particularly strong and the relationship of high blood pressure with other cardiovascular disease including heart attacks, heart failure and cardiovascular death is also very significant.
The evidence from large trials shows that the benefit of lowering blood pressure accrues very quickly after the blood pressure is lowered. Thus risk is higher when blood pressure is higher and lower when it is lower.
An example of the potency of the blood pressure and cardiovascular disease relationship was seen in 2004 a large study called the Valsartan Antihypertensive Long-term Use
Evaluation (VALUE) trial ( http://www.ncbi.nlm.nih.gov/pubmed/15207952 ). This study reported that good control of blood pressure early in the trial (within 3 months) was associated with reductions in the occurrence of strokes and deaths. The difference in blood pressure control in the first 3 months was only 3.8/2.2 mmHg but this reduction reduced strokes two-fold and deaths by almost three-fold.
Applied widely, initial treatment with two medicines could result in many hundreds of lives being saved in the UK alone.
Many patients with high blood pressure have other cardiovascular risk factors such as raised cholesterol or cigarette smoking or that they are older etc. Being at high risk means that events happen quite frequently such as 3-5 events occurring per year per hundred patients. In such patients a reduction in the rate of events by two or three fold results in very considerable benefit. So high risk patients tend to benefit more in terms of the number of events prevented than do low risk subjects.
ACCELERATE shows that there is no down-side to more aggressively lowering blood pressure earlier by using two medicines rather than one. Implemented widely to high risk patients this strategy has the capacity to save many lives and prevent other cardiovascular diseases.
4. Medicines used in the ACCELERATE study:
Amlodipine - Amlodipine works by relaxing blood vessels and so reduces the resistance of the circulation and subsequently reduces blood pressure. (Technically, amlodipine is a long-acting dihydropyridine calcium channel antagonist.)
Amlodipine is very widely used and is available as a 'generic' medicine (off-patent) and it is thus inexpensive. The Anglo Scandinavian Cardiac Outcome Trial (ASCOT http://www.ascotstudy.org/home.htm ) and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT http://allhat.sph.uth.tmc.edu/ ) studies provided good evidence for the efficacy of these medicines. More recently the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH http://www.nejm.org/doi/full/10.1056/NEJMoa0806182 ) trial found that amlodipine was superior to a diuretic medicine when co-prescribed with another medicine called an angiotensin converting enzyme inhibitor (ACEI).
Because of the findings of these studies amlodipine is now very widely prescribed for the management of raised BP.
Aliskiren - Aliskiren is a new medicine that acts by blocking the action of a hormone called renin. The kidney secretes renin and this works through a cascade of other hormones (called the renin, angiotensin, aldosterone system or RAAS) to cause the body to retain salt (sodium) and this results in an increase in BP. Blocking renin stops the cascade of other hormones from being activated and so stops the retention of salt. The effect of this is to reduce BP. Aliskiren is well tolerated and appears to be safe. Aliskiren is a novel patentable compound produced by Novartis pharmaceuticals and the trade names of this medicine are Rasilez in the UK and Tekturna in the USA.
5. British Hypertension Society: www.bhsoc.org
The British Hypertension Society provides a medical and scientific research forum to enable sharing of cutting edge research in order to understand the origin of high blood pressure and improve its treatment.