By Mark Greener, Freelance Medical Writer and Healthcare Communications Consultant

For years, the pharmacological management of stroke languished in the long shadows cast by heart disease. That could be about to change. As this tour shows, studies due for publication over the next few months go someway to clarifying strategies for primary and secondary stroke prevention, especially using lipid-lowering agents. Moreover, there's also renewed hope for neuroprotection in acute stroke, despite recent disappointments on this front.

Certainly, advances are needed. UK government statistics suggest that in 1998, the overall prevalence of ischaemic heart disease and stroke was 8.5% in men and 6.2% amongst women. During 1999, deaths from stroke accounted for 78.7 per 100,000 men and 130.7 per 100,000 women.

Indeed, across the developed world stroke is the third commonest cause of death and the leading cause of neurological disability. Approximately one-in-ten people who suffer an ischaemic stroke die within 30 days. Of those who survive, approximately half experience disability six months later. Against this background, a Decision Resources report estimates that sales of drugs for ischaemic stroke totalled $771 million in the major markets during 1998. Their analysts expect that combined sales of acute and secondary preventive therapies for stroke will reach nearly $1.5 billion during 2008.

In the meantime, as acute stroke treatment remains sub-optimal, much of the clinical emphasis focuses on primary and secondary prevention and numerous studies are underway. The Internet Stroke Center , hosted by Washington University School of Medicine, offers a comprehensive listing of stroke studies. In this tour, I will mention only some of the larger trials due to report over the next couple of years. But the Internet Stroke Center is also well worth visiting. You may well be surprised by just how active this area of research is.

Currently, clinicians tend to prescribe primary prevention with lipid lowering drugs for only either severe hypercholesterolaemia or moderate hypercholesterolaemia in patients with other risk factors. However, this advice might be refined following the publication of several studies assessing whether lipid-lowering drugs reduce vascular events in high-risk patients. For instance, FAME , PROSPER and RESPECT are examining the efficacy of fluvastatin, pravastatin and cerivastatin respectively.

Secondary prevention also attracts considerable interest from researchers - which isn't surprising given that 10 per cent of patients suffer recurrent stroke over the first year alone. In patients who have already suffered a stroke or transient ischaemic attack (mini-stroke), hypertension remains a risk factor for recurrence. Provisional evidence suggests that lowering blood pressure will reduce this risk. Against this background, PROGRESS is testing this hypothesis using the ACE inhibitor perindopril in 6000 patients. Similarly, several studies are assessing whether statins reduce the risk of further vascular disease, including HPS. (simvastatin) and SPARCL (atorvastatin).

The value of antiplatelet therapy after stroke or transient ischaemic attacks is better defined. But as aspirin reduces the risk of recurrent stroke by "only" 15 per cent, alternative antiplatelets are needed. Dipyridamole monotherapy appears to show similar efficacy against stroke as aspirin, although it does not seem to reduce the risk of myocardial infarction. Nevertheless, combining dipyridamole and aspirin is more effective than either drug alone against stroke. Aggrenox.com offers further information. Similarly, clopidogrel appears to be more effective than aspirin at reducing vascular events following a stroke, ischaemic heart disease or peripheral vascular disease. In this case, the efficacy is not limited to stroke prevention alone, but encompasses ischaemic heart disease and peripheral vascular disease. Again, a dedicated home page - Plavix.com - offers further information.

For years, researchers have searched for way to limit the damage arising from acute stroke. Indeed, neuroprotection has long been something of a holy grail for researchers. And they've searched along numerous pharmacological paths. The Internet Stroke Center offers a listing of the various approaches being tried - and I can only scratch the surface here. However, a few recent approaches exemplify neuroprotection's potential.

For example, Corvas International recently announced that its development partner Pfizer began a Phase IIb dose-ranging study of UK-279,276 (neutrophil inhibitory factor) in patients suffering acute stroke. Previous studies suggested that UK-279,276 is well tolerated and the new study includes functional and neurological outcomes. UK-279,276, a potent anti-inflammatory originally derived from hookworms that inhibits a specific neutrophil receptor, may prevent reperfusion injury in ischaemic stroke. Reperfusion of a necrotic area often triggers acute inflammation. This inflammation probably underlines much of the stroke-related brain damage.

Other approaches include opening potassium channels - a route followed by Bristol-Myers Squibb's BMS-204352 - or mopping up free radicals, an approach taken by Daiichi's Ebselen, Moreover, Pharmos Corporation recently showed improvements in long-term outcome, brain infarct size and mortality in rats subjected to experimental stroke and treated with the cannabinoid dexanabinol. Other cannabinoids in Pharmos' library show anti-inflammatory and neuroprotective efficacy in assays.

Despite being the third commonest cause of death in the major pharmaceutical markets, research into the treatment and prevention of stroke traditionally languished behind heart disease, cancer and other less deadly public health hazards, such as asthma or arthritis. It's not before time, but stroke at least seems to be on the verge of a therapeutic revolution driven by the studies visited on this tour - and many others. Whether any of the promising neuroprotective drugs in development reach the market remains to be seen. Nevertheless, the next couple of years will see results from several landmark studies in primary and secondary prevention. That alone is a cause for celebration.

We would be more than delighted if you would like to comment on this article. So please just contact Mark.

To make any comments on this article, or to ask a question of the author, please contact the publisher. If you would like to submit an article please subscribe to our PL Intelligence service.

The opinions expressed in the articles published in this section do not necessarily reflect those of Pharmalicensing or UTEK Corporation. No actions including proposals to or agreements with other companies should be taken by any reader without obtaining specific business or legal advice. Neither the publisher nor the authors accept any liability for any actions or activities undertaken by any reader or other third party as a consequence of these articles or for any errors or omissions therein.