Clopidogrel plus Aspirin reduces myocardial infarction risk in patients with acute coronary syndrome


In order to better prevent blood clots, Clopidogrel ( Plavix ) can be prescribed to patients with acute ischaemia of the heart muscle, in addition to Acetylsalicylic acid ( ASA ). The Institute for Quality and Efficiency in Health Care ( IQWiG ) has now investigated whether the combination of Clopidogrel and ASA actually has a higher benefit for patients than ASA alone. The final report by IQWiG, published on 31 March 2009, concludes that combination therapy can measurably reduce the risk of myocardial infarction. This particularly applies if the 2 drugs are used in the early stage of treatment.

ASA and Clopidogrel should complement each other's effects

Clopidogrel is an anti-platelet drug that is used in a similar way to ASA. It inhibits parts of the blood-clotting system, leading to a reduction in platelet clotting and of the subsequent formation of blood clots. Clopidogrel thus reduces the risk of occlusion of the arteries and helps prevent heart attacks and strokes. However, the risk of bleeding increases. As the mechanism that affects blood clotting is slightly different from that of ASA, Clopidogrel can also be used in combination with ASA in certain cases. It is assumed the 2 drugs complement each other and that the overall inhibitory effect on the formation of blood clots increases.

The combination of Clopidogrel and ASA is approved in patients with acute coronary syndrome ( ACS ), i.e., with an acute stenosis of the coronary blood vessels. On the one hand, this refers to patients with an acute myocardial infarction, which is shown in the electrocardiogram ( ECG ) as a characteristic elevation of the ECG wave between the "S" and "T" point ( ST-segment elevation myocardial infarction, STEMI ). On the other hand, it refers to patients with acute severe ischaemia of the heart, but without a myocardial infarction and the typical ST-segment elevation in the ECG. Both types of patients must as a rule immediately receive medical treatment in a hospital.

Patients with acute coronary syndrome without ST-segment elevation: Clopidogrel plus ASA has no effect on mortality

The results of the only study that could be assessed in patients with ACS without ST-segment elevation provided proof that patients using combination therapy experienced fewer heart attacks. In this study patients were treated for up to 12 months. All-cause mortality was not reduced by the additional use of Clopidogrel. At the same time, major bleeding complications occurred more often than with ASA monotherapy. It cannot be conclusively assessed, on the basis of the available data, how long it is meaningful for patients to use combination therapy in order for this therapy to be more beneficial than harmful. Specific studies are lacking here. Overall, however, patients seem to particularly benefit from combination therapy in the early phase of treatment.

Combination therapy in patients with STEMI/ACS can better prevent reoccurrence of a myocardial infarction

The evidence base is clear regarding the reoccurrence of heart attacks in patients with STEMI/ACS. The data provide proof that the additional use of Clopidogrel during the stay in hospital reduces the myocardial infarction rate more strongly than ASA alone does. However, it has so far not been proven that these patients benefit from taking both drugs after leaving the hospital. In addition, the data also provide indications that combination therapy in patients with STEMI/ACS is also more successful regarding the prevention of a stroke.

In contrast to patients with ACS without ST-segment elevation, the additional use of Clopidogrel in patients with STEMI/ACS could also have a beneficial effect on all-cause mortality. In the individual studies the results were inconsistent for this outcome; however, a meta-analysis showed a reduced mortality rate, which IQWiG evaluates as an indication of a benefit.

Patients with STEMI/ACS who use Clopidogrel also experience bleeding complications more often; however, these are usually minor. The studies also show that the starting point of therapy is important for treatment success. The data provide indications that patients particularly benefit from combination therapy if treatment starts not later than 6 hours after the first occurrence of symptoms.

Source: Institute for Quality and Efficiency in Health Care, 2009

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