2 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future.

2.1 In people who have not undergone revascularisation after an MI, does clopidogrel and placebo have a better outcome than clopidogrel and aspirin?

Why this is important

Standard antiplatelet therapy after an MI consists of dual therapy (DAPT) with aspirin and clopidogrel, which produces better outcomes than aspirin alone. Research has demonstrated that new P2Y12 inhibitors improve on the outcomes with clopidogrel, when combined with aspirin, although bleeding and subsequently risk are increased.

Few studies have used P2Y12 inhibitors without aspirin. There are theoretical reasons why aspirin may detract from the vascular benefits of strong P2Y12 inhibitors. In addition, because clopidogrel alone produces at least the benefit of aspirin alone, it is possible that the supposed benefit of the combination of clopidogrel and aspirin over aspirin alone is due solely to the action of clopidogrel. Limited data on the use of clopidogrel alone in people with vascular diseases suggests the possibility that the addition of aspirin to clopidogrel gives little or no reduction in vascular event rate, at the cost of an increased risk of bleeding. A study of clopidogrel alone compared with clopidogrel and aspirin in people after MI would be valuable because of the potential preserved benefit and reduced risk of bleeding. This might lead to new strong P2Y12 inhibitors being assessed without concomitant aspirin.

2.2 Does continuing beta-blocker treatment beyond 1 year after an MI improve outcomes for people with normal left ventricular systolic function?

Why this is important

Recent cohort studies have suggested that continuing treatment with a beta-blocker beyond a year after an acute MI may not confer any benefit to the person in terms of reduced morbidity or mortality. This is particularly relevant given recent changes in acute management strategies. While beta-blockers are valuable in reducing mortality and morbidity for up to a year after an MI, they have side effects and represent an additional treatment burden to people who are already taking many other medications. However, there is also some suggestion that there are risks associated with withdrawal of beta-blockers in this population. The balance of risks and benefits of long-term beta blockade has not been clearly determined, particularly in the context of modern acute treatment of MI.

2.3 Is treatment with an oral anticoagulant, aspirin and clopidogrel preferable to treatment with an oral anticoagulant and clopidogrel in people who have had an MI, have an indication for oral anticoagulation and are treated either medically, by primary PCI or by coronary artery bypass grafting surgery?

Why this is important

Many people who have had an MI have indications for long-term treatment with both oral anticoagulants and combination antiplatelet drugs. Those with atrial fibrillation, mechanical heart valves or a history of pulmonary emboli are at high risk of stroke or thromboembolism and therefore need anticoagulation to prevent these events. It is well recognised that people receiving a combination of antiplatelet therapy and oral anticoagulation are at high risk of minor, major and fatal bleeding events. These outcomes are often recurrent and associated with hospitalisation, blood transfusion and interventional procedures. The evidence review found limited high-quality evidence to identify whether, in this population, treatment with triple therapy (an oral anticoagulant, plus dual antiplatelet therapy) or dual therapy (an oral anticoagulant plus clopidogrel) is more effective. The Guideline Development Group recognised that this question was important in an increasingly elderly population, who are more likely to have comorbidities and who are at a higher risk of bleeding.

2.4 What characteristics are associated with uptake and adherence to cardiac rehabilitation after an acute MI when rehabilitation is started early?

Why this is important

There is wide variation across the UK in style, staffing and resources of cardiac rehabilitation programmes. Participation in cardiac rehabilitation after an acute MI significantly reduces mortality and improves quality of life. However, data from the 2012 Myocardial Infarction National Audit Project (MINAP) highlight that only 44% of all patients take part in cardiac rehabilitation after an MI. This falls far short of the National Service Framework for Coronary Heart Disease (2000) target of more than 85% of people discharged from hospital after an acute MI. National audit data also highlight that patients are waiting on average 53 days to start the exercise component (Phase III) after an acute MI. Early cardiac rehabilitation (defined as attendance at a cardiac rehabilitation orientation appointment within 10 days) significantly improves attendance and is also cost-saving through reduced incidence of unplanned cardiac re-admissions.

2.5 In people who have had a STEMI who undergo primary PCI with a bare-metal stent, and 4 weeks of aspirin and clopidogrel, is there an additional benefit to continuing clopidogrel for a further 11 months?

Why this is important

There are no randomised controlled trials that provide data on long-term treatment with clopidogrel plus aspirin compared with aspirin alone in patients who are treated with primary PCI or medical therapy alone. Two large trials have provided data on short-term efficacy in medically treated STEMI patients (Commit/CCS-2 and Clarity – TIMI 28). In clinical practice, doctors extrapolate the data from patients with NSTEMI, in whom this problem has been studied in both medically and invasively managed patients, who receive clopidogrel for up to 12 months (CURE, PCI-CURE, CREDO) because of a reduction in composite endpoints including mortality. The risk of bleeding increases with dual antiplatelet therapy (aspirin with clopidogrel), but the majority of benefit might occur in the short-term reduction of fatal and non-fatal re-infarction, and a reduced risk of stent thrombosis in patients treated with PCI.

  • National Institute for Health and Care Excellence (NICE)