6.3
Cardiovascular disease secondary prevention
See Background Chapter 6.3
Cardiovascular disease (CVD) is very common and will become even more common
and a serious public health problem over the next 20 years, particularly in developing
countries. In Europe, there are an estimated 80 million people who have a greater than
one in four, 10-year risk of a vascular event. Already, CVD is the leading cause of death
in Europe and the world (see Figure 6.3.1).
Figure 6.3.1: Deaths worldwide estimated for 2002 and projected for 2020
attributable to cardiovascular disease
40,000,000
30,000,000
20,000,000
2020
2002
10,000,000
Cardiovascular diseases
The determinants of CVD that have driven this epidemic of ill health in developed and
developing countries are well established. Smoking, high blood pressure, high
cholesterol, diabetes and obesity are among the most important risk factors for heart
attack and stroke. These risks are cumulative. Thus a smoker with high blood pressure
is at greater risk than a smoker with normal blood pressure. For patients who have
already had a heart attack or stroke, reducing these risk factors (irrespective of the level)
will dramatically reduce the risk of a repeat heart attack or stroke. This finding means
that even for surviving patients with normal blood pressure or normal cholesterol they
would benefit from medicines that reduce cholesterol or blood pressure.
There is evidence that lifestyle interventions, such as stopping cigarette smoking,
dietary change and increasing physical activity levels in patients with established
cardiovascular disease, are likely to reduce risks of recurrent vascular events. It is
likely that the beneficial effects of smoking cessation, increased physical activity and
dietary change will be largely independent and together they are likely to be
substantial. Although the benefits of specific lifestyle changes are clear and their costs
generally limited, the most efficient and cost-effective ways of bringing about these
changes in lifestyle have not been extensively investigated.
With regard to smoking cessation, advice from health professionals has been shown to
be effective. Although nicotine replacement therapy and antidepressant drugs have
short-term benefits in smoking
cessation
their
long-term
Suggested formulation for secondary prevention of
effectiveness is uncertain.
heart attack
It
has
been
clearly
 Low-dose antiplatelet therapy (for example
demonstrated that antiplatelet
aspirin 75mg)
therapy (with a medicine
 Full dose of a standard statin (for example
like aspirin), 1 blood pressure
simvastatin 40mg)
lowering
medicines
(ACE
 Full dose of an angiotensin converting enzyme
inhibitors or a diuretic) 2 , 3 and
inhibitor (for example lisinopril 10mg), and
 Half dose of a beta-blocker (for example atenolol
cholesterol lowering drugs
25mg)
(statins),4 used separately or in
combination, reduce the risk of
Suggested formulation for secondary prevention of
recurrent
vascular
events.
stroke
WHO has published two recent
 Low-dose antiplatelet therapy (for example
reviews which strongly support
aspirin 75mg)
the use of these medicines for
 Full dose of a standard statin (for example
secondary
prevention
(see
simvastatin 40mg)
Appendices 6.3).
 Full dose of an angiotensin converting enzyme

inhibitor (for example lisinopril 10mg), and
Half dose of a diuretic (for example
hydrochlorothiazide 12.5mg)
However, many patients with
existing
CVD
receive
substantially
incomplete
preventive
therapy.
The
problem is that, for a variety of reasons, these patients are not prescribed the four
different medicines they need to take. In 1999-2000, a major survey involving about 50
leading European hospitals identified major shortfalls in the secondary preventive care
provided to patients who had been admitted with ischaemic heart disease.5 Ideally,
each of the treatments should have been used in all patients but well under half of all
patients were receiving all the recommended treatments. Another feature of the data
was that there was only very limited improvement in treatment in comparison with a
comparable survey completed a few years earlier. This information reinforces the
need for novel strategies that will give physicians new ways of bridging the large
gaps between defined optimal care and actual clinical practice.
The simple solution to this deficiency is to develop and test a fixed-dose combination
(FDC) product of these proven effective medicines. The research agenda proposed in
this section is different to that of the other sections because this approach offers the
greatest potential short- to-medium term impact of all of the possible research activities
in this Report.
The evidence for the use of FDCs to improve adherence, reduce costs, improve access
and equity, and reduce medication errors for TB is convincing. However, to improve
the treatment of CVD, there is a need for the testing of new formulations of two
different, four-drug FDCs for the secondary prevention of heart attack and stroke (see
text box on the previous page). Once such products are formulated there will be a need
for clinical trials to assess the effect of these products on blood pressure, cholesterol
and platelet functioning, adherence to guidelines, and the overall effect on mortality
and morbidity. These trials should be undertaken in both developed and developing
countries.
While the EU Framework Programmes have not supported many clinical trials, trials
for these proposed FDCs should be an exception. Because the component medicines
are now off-patent, there is no incentive for innovative pharmaceutical companies to
undertake such trials, and the generic companies do not generally have the capacity to
do so.
It is estimated that these four-drug FDCs could reduce the risk of a second heart attack
or stroke by about two-thirds.6 If this combination proved effective, and cheap generic
versions of the individual medicines were used, this would be a very cost-effective
intervention.
On the basis of the background paper, it is strongly recommended that a research
agenda should be established to produce and test FDC products for secondary
prevention of heart attack and stroke to improve adherence and prevent mortality
and morbidity.
1
Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised
trials of antiplatelet therapy for prevention of death, myocardial infarction and stroke in
high risk patients. BMJ 2002;324(7329):71-86.
2
Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril
on cardiovascular and microvascular outcomes in people with diabetes mellitus: results
of the HOPE study and MICRO-HOPE substudy. Lancet 2000;355(9200):253-259.
3
PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood
pressure lowering regimen among 6,105 individuals with previous stroke or transient
ischaemic attack. Lancet 2001; 358(9287):1033-1041.
4
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of
cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized
placebo-controlled trial. Lancet 2002;360(9326):7-22.
5
Wood D, EUROASPIRE I and II Group. Clinical reality of coronary prevention
guidelines: a comparison of EUROASPIRE I and II in nine countries. Lancet
2001;357(9261):996-1001.
6
Wald N, Law M. A strategy to reduce cardiovascular disease by more than 80%. BMJ
2003;326(7404):1419-1425.