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Assessing Therapeutic Options and Individualising Treatment According to Patient Needs
events with ASA plus dipyridamole (419 [4.1%]) than with clopidogrel As determined in the ACTIVE W trial, warfarin is undoubtedly the
(365 [3.6%]). Furthermore, a greater number of patients discontinued recommended treatment for patients with AF who are at high risk of
the dual treatment than clopidogrel (1,650 [16.4%] and 1,069 [10.6%], stroke.
37
Nevertheless, the ACTIVE A study showed that in high-
respectively), with headache accounting for the greatest disparity.
45
risk stroke patients with AF who are unable or unwilling to take
Therefore, clopidogrel may be considered as a suitable treatment for warfarin, dual antiplatelet therapy with ASA and clopidogrel is an
this patient. effective alternative, with a 28% risk reduction for stroke.
37
Therefore,
in this patient, the dual antiplatelet therapy would be the first choice
Polyvascular Risk Patient of many physicians.
The second patient is a 67-year-old south Asian female from London.
She has non-insulin-dependent diabetes, hypertension, a history of Summary and Conclusions
stable angina and some claudication. She has also had a TIA within Several conclusions can be drawn from looking at these three clinical
the last 18 months and is taking ASA 75mg per day. Each of these can scenarios. First, ASA resistance is an important clinical phenomenon.
be considered to be an independent risk factor, and therefore she is a In these cases it can be beneficial to add dipyridamole, although an
classic example of a multivascular high-risk patient. alternative option is to use clopidogrel. Second, polyvascular
risk patients need to be treated very aggressively in order to
The REACH registry confirms that, despite conventional therapy, the minimise their future event rate. Finally, warfarin is the treatment of
risk of experiencing a major atherothrombotic event or of being choice in AF, but in a few patients where warfarin is a relative
hospitalised within one year is much greater if more than one disease contraindication, combined antiplatelet therapy of clopidogrel plus
bed is involved: 12.6% for single disease bed versus 21.7% for ASA is appropriate. n
multiple. The highest risk is for patients with CAD, CVD and PAD, at
26.3% (95% CI 23.8–28.7).
32
There is a linear relationship between the
Peter M Rothwell is a Professor of Clinical Neurology in
number of locations in which disease is present and the risk of
the Department of Clinical Neurology and the Stroke
subsequent vascular events (see
Prevention Research Unit at Oxford Neuroscience at
Figure 3). Furthermore, within this
risk hierarchy the presence of PAD doubles a patient’s risk of
the University of Oxford. He founded the Stroke
Prevention Research Unit in 2000 and his main
subsequent vascular events.
32
In the US at least, and almost certainly
research interests are in the causes of stroke and
worldwide, hospitalisation costs also increase with every vascular bed
improving the prevention of stroke, particularly after a
implicated (see
transient ischemic attack or minor stroke. He is also
Figure 6). Therefore, with this second patient it is
interested in the more general theme of how best to
important that her risk factors are aggressively managed.
apply the results of clinical trials and other forms of
research to clinical decisions with individual patients in
Pharmacological Treatment
routine clinical practice.
An aggressive treatment strategy for this patient includes statins to
Mark J Alberts is a Professor of Neurology and Director
manage her cholesterol. The Stroke Prevention by Aggressive of the Stroke Program at Northwestern University
Reduction in Cholesterol Levels (SPARCL) trial showed that high-dose
Feinberg School of Medicine and Northwestern
Memorial Hospital in Chicago, Illinois. His current
atorvastatin 80mg/day led to a 16% relative risk reduction in
research interests include studying genetic aetiologies
stroke/TIA. The authors of the paper added that stroke and TIA are of stroke, identifying new treatments for acute stroke
‘risk equivalents’ of CHD.
46
However, despite this, only around 17% of
and studying new medications and interventions to
prevent strokes. He has also been very active in
patients who are at high risk of ischaemic stroke are given statin
studying aspirin resistance in stroke patients. Professor
therapy. Moreover, even in a wealthy city such as London, patients Alberts assisted in establishing the Stroke Belt
from an ethnic minority – in this patient’s case, south Asians – are less
Consortium, a highly successful regional organisation to
improve stroke education.
likely to receive adequate statin treatment.
47
With diabetes, a 1%
reduction in glycated haemoglobin (HbA
1c
) is associated with a
Campbell D Joyner is a Professor in the Department of
relative risk reduction of 21% for any related diabetes end-point.
48
Medicine at the University of Toronto and an
Tight glucose control is likely to achieve good outcomes in stroke,
Associate Scientist in clinical integrative biology and
the Schulich heart research program at Sunnybrook
with a target HbA
1c
of <6.5%.
49
Similarly, there is a log-linear
Research Institute in Toronto. His research interests
relationship between the relative risk of first stroke and the mean include atrial fibrillation, congestive heart failure,
blood pressure. Even in the normotensive range of blood pressure of
aortic stenosis, high atherothrombotic risk and
ischaemic stabilisation management and avoidance.
75–85mmHg, this relationship holds.
50
Reducing blood pressure by
Professor Joyner is both a clinician and teacher
5mmHg leads to a 42% reduction in stroke risk.
51
Thus, by taking and is involved as a principal investigator in a number
medication to control her cholesterol, glucose levels and blood
of clinical trials.
pressure, this patient can reduce her stroke risk.
Pankaj Sharma is a Reader in Clinical Neurology at
Imperial College London and an Honorary Consultant
Atrial Fibrillation Neurologist at Hammersmith Hospitals. He was
The final patient is a more typical presentation. An 82-year-old man
formally the head of acute stroke services at
Hammersmith Hospitals Acute Stroke Unit (HHASU)
has a history of TIAs. An examination reveals hypertension and AF. The
and is now director of the Imperial College
patient has a relative contraindication to warfarin. Cerebrovascular Research Unit (ICCRU). His research
interests include the genetics of stroke, including in
Treatment
ethnic minority populations. He trained in general
medicine, clinical pharmacology and neurology, and is
Considering the patient’s relative contraindication to warfarin, the the only UK neurologist to hold specialist European
treatment options include ASA 75mg/day or 300mg/day, ASA plus
accreditation in the management of hypertension.
clopidogrel or warfarin anyway, despite the relative contraindications.
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