Ticagrelor With Invasive Strategy Cut Deaths


Major Finding: ACS patients with a planned invasive strategy who received ticagrelor had a 16% reduction in risk of cardiovascular death, MI, or stroke, compared with patients given clopidogrel over 1 year.

Data Source: 13,408 ACS patients in the PLATO trial who were scheduled for invasive procedures.

Disclosures: Funding by AstraZeneca, which makes ticagrelor. Dr. Stone, Dr. Cannon, and all of the study authors but one reported financial relationships with AstraZeneca.

Patients with acute coronary syndrome who received ticagrelor before an invasive cardiovascular procedure were 16% less likely to die from heart attack or stroke over the course of 1 year than were those given clopidogrel, according to a new subanalysis of the PLATO trial.

The benefit accrued without a significantly increased risk of bleeding and, unlike other early antithrombotic treatments, occurred in patients both with and without ST-segment elevation MI, investigators reported.

“This mortality benefit compared with clopidogrel is similar in magnitude to other major advances such as streptokinase or aspirin versus placebo, tissue plasminogen activator, and primary percutaneous intervention in care of patients with ST-elevation myocardial infarction,” wrote Dr. Christopher P. Cannon of Brigham and Women's Hospital, Boston, and his co-authors (Lancet 2010; DOI:10.1016/S0140–6736(09)62191–7).

“We estimate the use of ticagrelor instead of clopidogrel for 1 year in 1,000 patients with acute coronary syndromes who are planned to undergo an invasive strategy at the start of drug treatment would lead to 11 fewer deaths, 13 fewer myocardial infarctions, and six fewer cases of stent thrombosis,” they wrote.

In an accompanying editorial, Dr. Gregg W. Stone called the results a “landmark event that should redefine the care of patients with acute coronary syndromes.”

However, he cautioned against adopting them as a cookbook recipe for all ACS patients. “A personalized approach to drug selection should be used, wherein each patient's individualized risk of ischemia versus bleeding is considered,” wrote Dr. Stone of Columbia University Medical Center, New York. “Clopidogrel might still be appropriate for selected patients who are at relatively low risk of myocardial infarction or stent thrombosis and/or high risk of major bleeding and/or for whom noncompliance with ticagrelor because of cost or other considerations (such as twice-daily dosing) is a concern” (Lancet 2010: DOI:10.1016/S0140-6736(10)60070-0).

The PLATO (Platelet Inhibition and Patient Outcomes) study comprised 18,758 patients hospitalized for acute coronary symptoms and randomized to either clopidogrel plus placebo or ticagrelor plus placebo. This subanalysis focused on safety and efficacy in a subgroup of 13,408 patients for whom an invasive strategy was planned. Of these, 6,732 received ticagrelor (180 mg loading dose followed by 90 mg twice daily) and 6,676 received clopidogrel (300- to 600-mg loading dose followed by 75 mg/day). All patients received 75–100 mg aspirin/day. The follow-up period was 1 year.

The patients' mean age was 61 years; most were white (91%) and male (75%). About half had STEMI, 38% had non-STEMI, and 13% had unstable angina. For most, the invasive therapy included a coronary angiography (97%) and a primary percutaneous intervention (77%).

The primary efficacy end point was cardiovascular death, MI, or stroke. By the end of the follow-up period, the primary end point had been reached in 569 (9%) of the ticagrelor group and 668 (11%) of the clopidogrel group, showing a hazard ratio of 0.84 for the ticagrelor patients.

Ticagrelor was also significantly more effective than clopidogrel in a secondary composite end point of MI, stroke, and all cause-mortality (9% vs. 11%; HR 0.84).

It was significantly better than clopidogrel in patients with non-STEMI, reducing the risk of death by 17%. The 14% risk reduction seen in STEMI patients (8% vs. 9.5%) did not quite reach statistical significance. Both drugs similarly reduced the overall rate of stroke to 1%.

The rate of definite stent thrombosis was significantly lower in patients receiving ticagrelor (HR 0.64). Patients with a bare-metal stent reaped most of that benefit, experiencing a 38% reduction, compared with a 31% reduction in patients with a drug-eluting stent.

There were no significant between-group differences in the incidence of major bleeding (11.5% ticagrelor vs. 11.6% clopidogrel) or in life-threatening, fatal, or intracranial bleeding.

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