The new ADP receptor antagonists significantly reduce deaths and cardiovascular morbidity compared with clopidogrel in patients with stable angina or acute coronary syndrome managed invasively, a meta-analysis has shown. These benefits were achieved without a significant increase in bleeding complications.

The researchers identified eight randomised clinical trials comparing the new ADP receptor antagonists (prasugrel, ticagrelor and cangrelor) with clopidogrel in a total of 67,851 patients with stable angina or acute coronary syndrome.

Mean follow-up was 7.6 months, ranging from 48 hours to 30 months. Almost 70% of the patients were men, with a mean age of 62.4 years. The indication for dual antiplatelet treatment was mainly acute coronary syndrome. Coronary angioplasty was performed in 86% of patients.

The primary endpoint was mortality with secondary endpoints of nonfatal myocardial infarction, recurrent ischaemia symptoms or ischaemia-driven revascularisation or stent thrombosis. Safety endpoints related to major bleeding criteria.

The new ADP antagonists, compared with clopidogrel, produced significant reductions in:

• Mortality: 3.1% vs 3.6%, odds ratio (OR) 0.86 (95% CI:0.79-0.94),

P = 0.0008, with a greater impact from oral drugs

• Myocardial infarction: 6.1% vs 7%,

OR 0.88 (95% CI:0.79-0.98), P = 0.01

• Recurrent ischaemia: 2.7% vs 3.1%, OR 0.85 (95% CI:0.77-0.93),

P = 0.0005

• Stent thrombosis: 1.1% vs 1.7%,

OR 0.60 (95% CI: 0.51-0.71),

P <0.000001

Clopidogrel is now well established in the management of acute coronary syndrome. Improvements in stent technology allow the percutaneous treatment of more complex lesions and therefore expose patients to increased thrombotic risk.

Clopidogrel is far from perfect and the authors comment that 15% to 48% of patients may have inadequate platelet inhibition even with a 600 mg loading bolus and dose adjustment.

The new oral ADP receptor antagonists, prasugrel and ticagrelor, and the intravenous cangrelor are an interesting addition to the antiplatelet armoury.

These agents are regarded as having more potent antiplatelet activity than clopidogrel but were thought to have the potential to increase the risk of bleeding.

The authors conclude that the new ADP antagonists are associated with a significant reduction in mortality, reinfarction, recurrent ischaemia and stent thrombosis compared with clopidogrel, without significant increase in bleeding complications.

Despite the current cost differential I suspect that these drugs will supersede clopidogrel in the fullness of time.

Dr Peter Savill