NPC Archive Item: Update on glitazones and cardiovascular risks

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19 March 2010

In a recent Science Advisory, the American Heart Association and the American College of Cardiology Foundation have summarised the currently available data on the cardiovascular risks of glitazones and provided practical recommendations for health professionals.

In people with type 2 diabetes, priority should be given to reducing cardiovascular (CV) risk — lifestyle interventions (stopping smoking, losing weight, and taking more exercise as appropriate), controlling blood pressure, taking a statin, taking metformin.

In some patients, additional hypoglycaemic drugs may be considered to control blood glucose. However, NICE guidance on type 2 diabetes should be followed and individual targets for HbA1c should be agreed with each patient. These could be above that of 6.5% (48mmol/mol) set for people with type 2 diabetes in general and should take into account patient preferences and the balance of likely benefits and harms (such as hypoglycaemia) as well as the medicines management issues.

When considering prescribing a glitazone, health professionals should continue to follow MHRA advice published in October 2007 and December 2007. Neither pioglitazone▼ nor rosiglitazone should be used in people with heart failure or a history of heart failure. Rosiglitazone should be used in patients with previous or current ischaemic heart disease (IHD) only after a careful evaluation of the individual patient’s risk. Furthermore, neither glitazone should be commenced or continued in people at higher risk of fractures.

What does this Science Advisory say?
The Advisory says that “Thiazolidinediones [glitazones] should not be used with an expectation of benefit with respect to IHD events. Insufficient data exist to support the choice of pioglitazone over rosiglitazone. Thiazolidinediones increase the risk of heart failure and should not be initiated in patients with NYHA class III/IV CHF”

There has been only one prospective RCT specifically designed to assess the effect of rosiglitazone on CV outcomes — the RECORD study. However, due to study limitations the results relating to CV risks are inconclusive. Meta-analyses of RCTs have also reported inconsistent results. The Advisory concludes that an association between rosiglitazone and IHD has not yet been firmly established, although sufficient evidence has emerged to raise concerns about a potential adverse effect.

The majority of published studies on pioglitazone (including the PROactive study) do not suggest an increased risk of CV events. However, there are currently no prospective RCTs that have examined the risk of CV events associated with pioglitazone compared with rosiglitazone and observational studies have reached different conclusions. The Advisory also comments on the well established effects of glitazones in exacerbating heart failure.

The Advisory recommends that the essential components for prevention of CV events in patients with type 2 diabetes include smoking cessation, maintenance of optimal body weight, diet, physical activity, control of blood pressure and lipids (with statins as first-line therapy), and use of aspirin (see our blog which discusses recent data on the effectiveness of aspirin for primary prevention in patients with diabetes). These interventions are of proven benefit in reducing macrovascular disease and saving lives. There is however, a paucity of evidence that any hypoglycaemic drug reduces macrovascular risk, and there are questions about whether rosiglitazone or intensive glycaemic control may have adverse effects on risk for IHD. Of the available agents, metformin in obese patients with type 2 diabetes has provided the strongest evidence of CV disease benefit.

The Advisory concludes by saying that clinical trials focusing purely on glycaemic control as the primary outcome do not provide the quality of evidence required to make informed decisions regarding the efficacy and safety of glucose-lowering regimens with respect to both microvascular and macrovascular disease. More data are needed to clarify the effects of all existing and future glucose-lowering agents on CV events.

More information on the choice of hypoglycaemic drugs can be found on the type 2 diabetes section of NPC.

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