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Prescribing Advice for GPs

An NHS Prescribing Advisers' Blog


NICE published a Clinical Guideline for Hypertension in August 2004. This guideline was based on the evidence available at the time and was probably dramatically influenced by the ALLHAT Study1.

This Study was conducted in about 42,000 patients and compared active treatments as follows:

  • Thiazide Diuretic (Chlorthalidone)
  • ACE Inhibitor (Lisinopril)
  • Calcium Channel Blocker (Amlodipine)
  • Alpha Blocker (Doxazosin)

Based upon the results of this trial there are two key findings that altered (or should alter) daily practice. Firstly, the Doxazosin arm of this study was stopped early as patients in this group were suffering more outcome events than any other arm. It was therefore decided it was unethical to continue this arm of the study and as a consequence of these steps Doxazosin is a fifth line antihypertensive agent.

The ultimate finding of the study was that there is little to choose between the remaining three arms in terms of clinical efficacy in terms of "hard" outcomes like fatal and non-fatal MI. There were differences in blood pressure control between the groups where the Thiazide Diuretic performed well against the other drugs with amlodipine proving better in diastolic pressure only. While the differences are statistically significant, the clinical differences are negligible (0.8 - 2mmHg difference).

This then leaves the only difference for evaluation between the drug arms to be that of cost. As Thiazide Diuretics as the most cost effective option there simply must be the first line treatment for hypertension.

Second line options are added based upon emerging evidence around the risk of diabetes when Beta Blockers are used in conjunction with Thiazide Diuretics. Angiotensin Converting Enzyme Inhibitors (ACEIs) are preferential in those patients who are at higher risk of developing diabetes.

Action: The NICE Guideline is evidence based and should be followed by all clinicians treating Hypertension in Primary Care. For full details of the algorithm, see the Clinical Guideline Quick Reference.

For each of the NICE recommended drug classes the following drugs are recommended:

  • Thiazide Diuretic - Bendroflumethiazide 2.5mg
  • Beta Blocker - Atenolol 50mg or Bisoprolol 5mg
  • ACE Inhibitor - Ramipril or Perindopril (Titrated to maximum tolerated dose)
  • Calcium Channel Blocker - Amlodipine (as Mesilate) or Felodipine

ONLY if ACE Inhibitor is not tolerated

  • Angiotensin II Receptor Blockers - Candesartan or Irbesartan or Valsartan


  1. 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). The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group JAMA 2002;288:2981-2997

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A recommendation has already been made regarding changing statin therapy following the implementation of the new Pharmacy Contract.

There is much discussion at present about the likely changes to the GMS contract and the targets contained within it regarding cholesterol. Broadly speaking there are two sides to the argument, the "fire and forget" approach and the "treat to target" approach. The treat to target approach is firmly contained in the current contract and rumours abound that the target is likely to be lowered for next year. The evidence to support this approach is growing but as yet is not entirely persuasive.

It would be prudent in any eventually to take a stepped approach to treatment to ensure that whatever happens, prescribers are prepared to tailor treatments to gain maximum benefit for as many patients as possible. Using the most cost effective and evidence based statins as first line will help to achieve this goal.

The 4S1 and HPS2 studies have shown that Simvastatin is an effective and well tolerated drug. It reduces cholesterol by 30% at the 40mg strength and has evidence to prove its benefits in saving patients lives. Simvastatin is unprecedented as the choice for lipid lowering.

In situation where Simvastatin 40mg does not get the patient to the required target, first consider if the patient is taking the medication and if they are still eating a healthy diet before altering the treatment. Where a treatment alteration is required, Atorvastatin 40mg is a more potent cholesterol reducing agent albeit with a lower level of evidence in terms of cardiovascular event outcomes.

Finally, if Atorvastatin 40mg fails to attain prescribers should consider the most appropriate way forward for the patient in question. Options include accepting the current cholesterol level, increasing the dose of the statin, adding in another lipid lowering agent or referring to a specialist.

Action: Implement and use a stepped approach to lipid management as follows:

  • Simvastatin 40mg tablets, 1 each day
  • Atorvastatin 40mg tablets, 1 each day
  • Revert to Simvastatin 40mg tablets and add Ezetimibe 10mg tablets, 1 each day

    Or Increase to Atorvastatin 80mg tablets, 1 each day

    Or Refer for specialist advice


  1. The Scandinavian Simvastatin Survival Study Group. Randomized Trial of cholesterol lowering in 4444 patients with coronary heart disease. Lancet 1994;344:1383-1389
  2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7-22M

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Antiplatelets should be prescribed to reduce the risk of a cardiovascular event. This risk reduction can be classified as primary or secondary prevention depending on whether the first or subsequent event is being prevented. The evidence for the most appropriate intervention differs between these two groups.

Secondary Prevention is the reduction of risk of a subsequent cardiovascular event, for example a heart attack or stroke. NICE have recently issued a Technology Appraisal on this topic.

The guidance states the following:

  • Low dose Aspirin (75mg [Dispersible]) is "standard care"
  • In patients who have had an ischaemic stroke or a transient ischaemic attack, the combination of modified-release dipyridamole and aspirin (Asasantin) is recommended for two years after the most recent event
  • Only in patients who are intolerant to aspirin should clopidogrel (Plavix) be used (within the product license)

Primary Prevention is the reduction of risk of a first event. The NICE Technology Appraisal detailed above does not cover this population. In this group of patients the expected risk reducing benefits must be weighed against the potential risks associated with the treatment. It is also important to pay due regard to product licenses. Neither Asasantin nor Plavix are licensed for Primary Prevention.

An article on Bandolier has provided a sensible and evidenced approach to balancing the risks and benefits. This article concludes that at a coronary risk of 1.5% per year (or 15% in 10 years, or a CVD risk of 20% in 10 years) the benefits outweigh the risks.

Patients who are at a greater than 20% risk of their first CVD event in the next 10 years should be offered antiplatelet therapy with Low Dose Aspirin (provided their blood pressure is controlled and there are no contraindication)

Action: Prescribers should use Aspirin 75mg Dispersible as first line treatment for prevention of cardiovascular events. Where compliance is to be affected by gastrointestinal symptoms an Enteric Coated formulation can be tried before the alternative strategies listed above.

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