#105 The new anti-platelet ticagrelor: Is it better than the old “new” clopidogrel?

CLINICAL QUESTION

QUESTION CLINIQUE

How does the newer anti-platelet drug ticagrelor (Brillinta®) compare to clopidogrel for post-acute coronary syndrome (ACS)?

BOTTOM LINE

RÉSULTAT FINAL

After ACS, ticagrelor reduces combined cardiovascular death, stroke, and myocardial infarction (MI) about 2% more than clopidogrel. Ticagrelor increases a few adverse events, particularly 6% more dyspnea, and effectiveness remains uncertain in North America.

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EVIDENCE

DONNÉES PROBANTES

PLATO, multinational Randomized Controlled Trial (RCT) of 18,624 patients hospitalized for ACS +/- ST elevation, comparing ticagrelor vs. clopidogrel (both with usual care including ASA) for 12 months maximum,^1,2 found statistically significant reduction in:

Primary endpoint (composite of cardiovascular death, MI, or stroke), Number Needed to Treat (NNT) 53.
Other outcomes better:
- Recurrent MI: NNT 91.
- Death from vascular causes: NNT 91.
- Death from any cause: NNT 71.
- No significant difference in stroke.
Adverse reactions:
- No significant difference in any bleeding except:
  - Bleeding worse when coronary artery bypass patients excluded, Number Needed to Harm (NNH) 143.
  - Worse fatal intracranial hemorrhage, NNH 926.
- Any dyspnea, NNH 17; Requiring discontinuation, NNH 125.
- Non-fatal arrhythmias (ventricular pauses) were significantly increased with ticagrelor as well.³
Subgroup analysis of 1,800 patients in PLATO from North America showed much less favourable results: mortality was actually lower in clopidogrel group at 12 months.^2,3

Context:

Ticagrelor has several theoretical benefits over clopidogrel: it is a reversible platelet inhibitor, hepatic metabolism not required for activation (less intra-individual variability in response), and faster onset/offset of action.^3,4
Benefits of ticagrelor seem maintained in higher risk groups like those with renal insufficiency⁵ and diabetes.⁶
- Ticagrelor proposed as an alternative in clopidogrel non-responders.⁷
Unanswered concerns:
- No clear explanation why ticagrelor worse in North America.⁸
- Dyspnea unexplained³ but is not associated with structural cardiac damage or pulmonary function test abnormalities.^9,10
Ticagrelor is significantly more expensive than clopidogrel ($310/90 days vs. $100/90 days)¹¹ and requires twice-daily dosing.
Given the cost, increased harms, and uncertainty around effectiveness in North America, clinicians should:
- Consider clopidogrel a reasonable alternative in intolerant patients started on ticagrelor in hospital.