Published: 15/07/2004, Volume II4, No. 5914 Page 24 25

Drugs to combat blood pressure may come at a price, but the wider health benefits should not be underestimated, says Nick Summerton

Once upon a time the citizens of Chesterfield would have been proud of the new Church of St Mary and All Saints.However, as a result of using cheaper unseasoned timber, the church is now better known for its twisted spire. This rises 228ft above the town like a crooked finger reminding us all of the need to consider consequences as well as costs.

This is well illustrated in the prevention of cardiovascular disease. Echoing the coronary heart disease national service framework, the new general medical services contract quality framework places a special emphasis on the pro-active management of hypertension and diabetes. Solutions being developed range from service innovations - care pathways, primary care clinicians with special interests and public health initiatives - through to new pharmacological approaches to modify cardiovascular risk factors such as blood pressure.

There is a tradition of adopting a broader perspective in developing a public health view on cardiovascular disease prevention. For example, smoking cessation programmes are considered to have added health value beyond their impact on cardiovascular disease. It is disappointing that pharmacological interventions are often not accorded the same degree of consideration.

The angiotensin receptor blockers such as Valsartan, Losartan and Candesartan represent a major advance in the management of cardiovascular disease. By specifically blocking the angiotensin 1 receptors and leaving the angiotensin 2 receptors unaffected, it has been suggested that this group of drugs have advantages over treatments such as the calcium channel blockers, the beta blockers, the ACE inhibitors and the diuretics for cardiovascular disease treatment and prevention.

A series of randomised controlled trials have revealed significant benefits for the angiotensin receptor blockers for the management of heart failure.More importantly, they have an impact on the management of other chronic diseases such as diabetes. Losartan and Irbesartan may prevent the progression of renal disease, irrespective of the effects on blood pressure.

The most recently published angiotensin receptor blocker trial, VALUE, involved 15,000 patients with high blood pressure who were also representative of the types of patients most GPs are likely to encounter in day-to-day practice at elevated cardiovascular risk.

1One-third were diabetic, one-quarter were smokers and half had a history of coronary heart disease. This is in stark contrast to the groups of patients included in randomised controlled trials.

The problem with the angiotensin receptor blockers is that they are not cheap.

According to a recent edition of the British National Formulary, one month's supply (28 capsules) of Valsartan 80mg costs£15.75 and yet a month's supply of the beta blocker Atenolol costs£1.01. The diuretics are even cheaper: 20 tablets of generic bendroflumethiazide retail at 53p.

In its draft hypertension guidance, the National Institute for Clinical Excellence is proposing that thiazide diuretics should be the first choice in hypertension treatment, with angiotensin receptor blockers being relegated to second or third choice. But in considering whether angiotensin receptor blockers should be prescribed for a patient a much broader perspective is needed.

The commonly prescribed anti-hypertensive drugs produce a range of side effects, including lethargy, gout, cough and impotence. As a result, not all patients will tolerate the first anti-hypertensive treatment they are prescribed; reported one-year cessation rates are 12.9 per cent for thiazide type diuretics, 17.6 per cent for ACE inhibitors and 27 per cent for beta blockers.

More worryingly, over the longer term some patients may simply remain undertreated as a consequence of either stopping or reducing their treatment with or without the implicit agreement of their doctor.

A dramatic review in the Lancet suggested that twothirds of the cerebrovascular disease burden and half the ischaemic heart disease burden is attributable to sub-optimal blood pressure control.

2The VALIANT trial examined whether the angiotensin receptor blocker Valsartan was a realistic alternative to Captopril in the management of patients following a myocardial infarction.

3Although the drugs were equivalent in terms of effectiveness, the overall level of side-effects was lower in the Valsartan-treated group, with 83 fewer patients discontinuing treatment.

Similarly, in the VALUE hypertension trial Valsartan and Amlodipine (a calcium channel blocker) had similar effects on cardiac morbidity, but patients on Amlodipine were significantly more troubled by ankle swelling.

1Such swelling is dose-dependent and as we are encouraged to manage blood pressure more aggressively to reduce overall cardiovascular risk this side effect may become more of a difficulty.

Nowadays patients are encouraged to understand more about their care. Furthermore, as time passes and some patients with hypertension accumulate additional problems such as diabetes, the potential harm of some treatments may begin to outweigh their benefits. In the VALUE trial, Amlodipine resulted in more hospital admissions with heart failure than Valsartan.

1Drugs often have multiple effects, and in the management of blood pressure it is important to appreciate that this is only a surrogate marker of longer-term effectiveness.What really matters is the ability of the treatment to reduce overall cardiovascular risk as measured by the impact on cardiovascular morbidity and mortality.

The LIFE trial compared the angiotensin receptor blocker Losartan against the beta blocker Atenolol in patients with high blood pressure.

4Interestingly this demonstrated that patients treated with Losartan gained additional benefits in terms of cardiovascular risk reduction beyond that due to blood pressure reduction alone. The authors suggested that Losartan might have an additional cardioprotective effect.

In common with high blood pressure or elevated cholesterol, diabetes is an important independent risk factor for cardiovascular disease. In both the LIFE and VALUE trials, patients with hypertension treated with an angiotensin receptor blocker were significantly less likely to develop diabetes.

1,4 The effect was particularly dramatic in the VALUE trial where the reduction was 23 per cent. It therefore seems that Valsartan impacts on at least two major risk factors - it lowers blood pressure and, independently of that, reduces the incidence of new onset diabetes.

Preventing cardiovascular disease should be about longer-term planning. In considering pharmacological approaches such as the use of the angiotensin receptor blockers, a broader perspective should be adopted. There is a need to consider both drug costs and the requirement for continuing treatment over an extended period to reduce cardiovascular risk.

Good-quality care of people with hypertension is about considering a drug's acceptability to the patient, appropriateness and efficiency as well as effectiveness.

Coupled with this there is a need for greater awareness that drugs may have more than one effect and that patients may have more than one chronic condition. l Dr Nick Summerton is a GP and reader in public health and primary care at the University of Hull.

References

1Julius S et al .Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial.Lancet 2004; 263: 2022-31.

2Blood pressure lowering treatment trialists collaboration.Effects of different bloodpressure-lowering regimens on major cardiovascular events.Lancet 2003; 362:1527-1535.

3Pfeffer MA et al .Valsartan, captopril or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.The VALIANT trial.New England Journal of Medicine 2003;349:1893-1906.

4Dahlof B et al .Cardiovascular morbidity and mortality in the Losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.

Lancet 2002; 359:995-1003.

Key points

New anti-hypertensive drugs, although more expensive than conventional treatments, have significant benefits in the management of cardiovascular disease.

NICE analysis of cost-benefits do not consider their impact on other risk factors for cardiovascular disease, such as diabetes.

A broader perspective is necessary when assessing the public health benefits of anti-hypertensive drugs.