ASCOT

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ASCOT
ASCOT STUDY
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ASCOT

• INTRODUCTION AND AIMS
• EXISTING KNOWLEDGE
• BACKGROUND OF ASCOT
• STUDY DESIGN (TWO ARMS (BPLA,LLA)
• METHODOLOGY
• TREATMENT REGIMES USED IN ASCOT
• RESULTS (BPLA published in 4/9/05)
• CHANGE IN GUIDELINES ??
• HOW DOES IT AFFECT GPS ??

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INTRODUCTION

• Largest study of high blood pressure treatment
  ever conducted in Europe.
• Results were published in the European Scoiety of
  cardiology in September 4th 2005.
• Combination of effective modern antihypertensives
  along with lipid lowering drugs can reduce the
  incidence of strokes CHD, cardiovascular deaths
  and prevent the onset of diabetes.

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INTRODUCTION AND AIMS

• Launched in 1997 funded by Pfizer
• Independent investigator led study
• Designed to evaluate different treatment
  strategies for preventing cardiovascular disease
  in hypertensive patients.
• Compare the effects of two treatment strategies
  on non fatal MI and fatal CHD.

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EXISTING KNOWLEDGE

• Hypertension is one of the most prevalent risk
  factors for cardiovascular disease, affecting 800
  million people worldwide.
• At least 80 of these would have other
  uncontrolled risk factors of which raised
  cholesterol is the commonest.
• We all know that reduction of blood pressure is
  central to reducing mortality due to MI, CVA etc.
• Traditionally beta blockers diuretics are used
  to treat hypertension
• Newer drugs like calcium channel blockers and ACE
  inhibitors are also used to treat hypertension.

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BACKGROUND

• Conducted in 650 practices and 32 regional
  medical centres in the UK, Ireland and the 5
  Scandinavian countries.(Denmark, Norway,
  Sweden,Iceland and Finland)
• The impetus of this study was lack of outcome
  data on the newer types of antihypertensives.

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BACKGROUND contd

• No evidence so far on the outcome of specific
  combination regimes in lowering blood pressure.
• Evidence of shortfall in the prevention of CHD
  using standard therapies using beta blockers and
  diuretics.
• Need to evaluate multiple risk factor
  intervention in the prevention of CHD.
• Previous trials have shown that beta blockers and
  diuretics are better than hydrallazine and
  methyldopa.(these are no longer commonly used)

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DESIGN

• Multicentric international trial that involves
  two treatment comparisons in a factorial design.
• A prospective, randomized open blinded ,end point
  design study (PROBE) comparing 2 antihypertensive
  regimens (BPLA)
• A double blind, placebo controlled trial of a
  lipid lowering agent in a subsample of those
  hypertensive patients.(LLA)

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METHODOLOGY

• 19,257 patients in the age group of 40-79 years
  were recruited between 1998-2000.
• Other eligibility criteria were
• No contraindications to the drugs
• Able to attend clinic regularly for 5 years
• BP gt160/100 untreated or gt/ 140/90 treated.
• No previous MI or CHD
• 3 or more risk factors for cardio vascular event
  i.e. smoking, NIDDM, Male, age gt55.

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Treatment regimes BPLA

• The trial protocol was to reduce the BP to 140/90
  in non diabetic and to 130/80 for diabetics.
• The 2 antihypertensive regimes were administered
  in 6 incremental steps, depending on whether
  patients achieved their goals.
• First line drugs were amlodipine or atenolol,
  followed by combination with perindopril or
  bendrofluazide.

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REGIMES contd
Step 1 Amlodipine 5 mg Atenolol 50 mg
Step 2 Amlodipine 10 mg Atenolol 100 mg
Step 3 Amlodipine 10 mg Atenolol 100 mg
Perindopril 4 mg BFZ 1.25 mg
Step 4 Amlodipine 10 mg Atenolol 100 mg
Perindopril 8mg BFZ 2.5 mg
Step 5 Amlodipine 10 mg Atenolol 100 mg
Perindopril 8 mg BFZ 2.5 mg
Doxazosin 4 mg Doxazosin 4mg
Step 6 Amlodipine 10 mg Atenolol 100 mg
Perindopril 8 mg BFZ 2.5 mg
Doxazosin 8 mg Doxazosin 8 mg
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RESULTS

• 9639 patients received Amlodipine/ Perindopril
  treatment regime.
• 9618 patients received atenolol/ Bendrofluazide
  treatment regime.
• 18 were already on Asprin
• 10 were on lipid lowering drugs.
• Median follow up was 5.4 years.
• Only 14 of patients on the amlodipine group and
  9 of patients on the atenolol group remained on
  monotherapy.

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RESULTS contd.

• Blood pressure was well controlled in both arms
  of the study, but lower in the amlodipine group.
• Average BP before the study for the amlodipine
  group was 164.1/94.8, which was reduced to
  135.5/71.1 after 5.4 years.
• For the atenolol group blood pressure dropped
  from 163.9/94.5 to 136.3/78.4.

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RESULTS contd.

• 14 risk reduction in all cause mortality in the
  amlodipine group
• 10 reduction in the primary endpoint of nonfatal
  MI or fatal CHD.
• 23 reduction of fatal and non fatal stroke.
• 24 reduction in cardiovascular mortality.
• 16 reduction in total cardiovascular events and
  revascularisation procedures.

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RESULTS contd.

• 32 excess incidence of new onset diabetes on the
  atenolol group.
• Reduction in the incidence of renal impairment
• Reduction in the incidence of peripheral vascular
  disease.

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RESULTS (LLA)

• Study was terminated after a median period of 3.3
  years by the data and safety monitoring board as
  there was significant reduction in the primary
  endpoint as well as in the incidence of strokes.
• Total of 10,297 of the patients enrolled in the
  ASCOT were eligible for the lipid lowering arm of
  the study.

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RESULTS LLA (contd)

• 36 reduction in non fatal MI and fatal CHD.
• 27 reduction in fatal and non fatal stroke
• 41 reduction in chronic stable angina.
• 13 reduction in total mortality.
• 21 reduction in revascularisation procedures
• 29 reduction of total cardiac events.

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CHANGES TO GUIDELINES??

• Professor Peter Littlejohns, NICE Clinical and
  Public Health Director, commented
• NICE guidelines are not usually considered for
  updating until four years after publication.
• However in this case, because a potentially
  significant piece of new evidence is about to be
  published, NICE feels it is appropriate to look
  at this data in the context of our existing
  recommendations to see whether any revision might
  be necessary.

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CONTD

• Professor Bryan Williams, a member of the
  Guideline Development Group added Early
  indications from the ASCOT study suggest that the
  results have the potential to change the
  pharmacological treatment algorithms in the
  current NICE and BHS guidelines.

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HOW DOES THIS AFFECT GPS

• Adds to the existing confusion.
• BHS guidelines downgraded the use of beta
  blockers as first line treatment.
• NICE still recommend beta blockers and thiazide
  as first choice.
• ASCOT recommends amlodipine and perindopril.
• Cost implications.