CARDS study halted due to benefit of atorvastatin in patients with type 2 diabetes

Susan Jeffrey

June 18, 2003

Wed, 18 Jun 2003 19:30:00

New Orleans, LA - The Collaborative Atorvastatin Diabetes Study (CARDS), comparing treatment with atorvastatin (Lipitor®, Pfizer Inc) with placebo in 2800 patients with type 2 diabetes but without overt heart disease, has been halted two years earlier than planned because of a significantly lower incidence of fatal and nonfatal coronary events, stroke, and coronary revascularization procedures in treated patients.

The CARDS steering committee announced on June 16, 2003 that the study was being stopped early because an interim analysis showed a "substantial and highly significant benefit of treatment," they note in a press release. Carried out in 132 centers in the UK and Ireland, CARDS is a collaboration between the University College of London; Diabetes UK, a diabetes charity; the Department of Health; and Pfizer UK.

"These are very promising results and the final data will be available in the next few months, late this year or early next year," co-principal investigator Prof Helen M Colhoun (University College and Middlesex School of Medicine, London, UK) told heartwire . "If the final data confirm our current findings (as we expect them to), then taken together with the data from HPS and ASCOT, it would provide a strong evidence base to underpin a change in CVD-prevention guidelines that would affect a large proportion of type 2 diabetic patients."

Recent NICE guidelines in the UK, for example, considered the evidence base to be weak for patients with a 10-year CHD risk below 15%, Colhoun added, and so did not make a clear recommendation of lipid lowering for these patients.

Change of practice in the CARDS?

CARDS is a multicenter, placebo-controlled, double-blind study that enrolled 2838 men and women between 40 and 75 years of age and randomized them to receive 10 mg/day of atorvastatin or placebo. Patients had type 2 diabetes as well as one other risk factor for coronary heart disease, including current smoking, hypertension, retinopathy, or microalbuminuria or macroalbuminuria. Serum LDL had to be <160 mg/dL and triglycerides <600 mg/dL.

The trial was to continue until 304 primary end-point events had occurred, which was not expected until 2005, according to the published protocol.

CARDS is the second atorvastatin trial to be ended early. Late last year, the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was stopped after 3.3 years of a planned five-year follow-up for a significant reduction in cardiovascular outcomes among hypertensive patients with normal cholesterol levels who were on treatment. Results of that trial were presented in March at the American College of Cardiology 2003 Scientific Sessions and reported at that time by heartwire .

The positive effects of statin treatment in people with diabetes were also confirmed by results of the Heart Protection Study (HPS), recently published in the Lancet. In that study, treatment with 40 mg/day of simvastatin (Zocor®, Merck) cut the incidence of MI, stroke, and revascularization in the diabetic subgroup of about 6000 patients by one third, approximately the same benefit as that seen in the overall HPS population.

The findings had the HPS researchers calling for a change of diabetes guidelines as well.

"The present study provides direct evidence that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations," said lead author Dr Rory Collins (Clinical Trial Service Unit, Oxford, UK). "Statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events, irrespective of their initial cholesterol concentrations."

Stopping short of treatment for all?

In an interview with heartwire , Dr Darren McGuire (University of Texas, Southwestern, Dallas) said the early termination of CARDS due to overwhelming efficacy and the previously published data from the diabetic cohort of HPS and from ASCOT all strongly support lowering the threshold for treatment among people with diabetes. "The accumulated data are consistent and very impressive, making it clear that the vast majority of patients with type 2 diabetes should be treated with a statin," McGuire said. "But I think we have to stop just short of advocating statins for all patients with type 2 diabetes for two main reasons."

First, he says, although diabetes markedly increases CV risk, there remains a population, albeit a small group, in whom the magnitude of risk does not translate into cost-effective treatment: younger patients with no other CV risk factors, for example. "Even with a consistent relative risk reduction associated with statins in this lowest-risk group, as overall risk shrinks, so will the absolute risk reduction, requiring much larger 'numbers needed to treat' to realize benefit." In these patients, the decision to treat should hinge on an estimate of their overall cardiovascular risk, McGuire says.

The other group in question is the growing population of children who are now developing type 2 diabetes; in the US, the prevalence of type 2 in children is approaching that of type 1, a trend now seen around the world. "The proposition of treating an 11-year-old patient with diabetes to be continued lifelong raises additional issues of cost effectiveness, treating through puberty, and longer-term safety," he said.

Related links

1. HeartWire > News; June 12, 2003]

2. [Education > HeartBeat; Apr 17, 2003]

3. [HeartWire > News; Apr 2, 2003]


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