Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction

Antiplatelet therapy is recommended in all patients with acute coronary syndrome (ACS) regardless of their revascularization strategy. [1, 2] Registries and observational studies are an important source of information on the efficacy and safety of medication under clinical practice conditions. The ‘System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry’ is a nationwide coronary care unit registry recording baseline characteristics, treatments, and outcome of consecutive patients with ACS admitted to all hospitals in Sweden. The present article addresses ticagrelor or clopidogrel treatment among this large population. [3]

This observational study aimed to gain a comprehensive overview on the efficacy and safety of these two P2Y12 receptor inhibitors used for the treatment of ACS, with the focus on the use of P2Y12 receptor inhibitor-based dual antiplatelet therapy (DAPT), patient selection, and outcomes.

Then mean age in SWEDEHEART patients was similar to that reported in other registries such as CZECH-2, DIOCLES and FAST-MI, and those individuals discharged on ticagrelor were significantly younger than those on clopidogrel (67.0 vs 71.0 years).

Mean age, percentage of women, and NSTEMI increased in both groups over time. This is important as the baseline differences between patients receiving ticaglelor and clopidogrel included age (67 vs. 71 years), sex (71.5 vs. 65.2% males), ACS type (46.7 vs. 31.4% STEMI), and intended duration of DAPT.

In contrast to the PLATO trial, [4] mortality included in the primary and secondary endpoints was ‘all cause’ instead of ‘death due to vascular causes’ (see Table 1).

Table 1: Main results from the PLATO trial [4] and SWEDEHEART registry [3] in terms of endpoint reduction as derived from treatment with ticagrelor with respect to clopidogrel.

The PLATO trial found no significant differences in the bleeding rates between ticagrelor and clopidogrel groups (11.6% vs 11.2%; p=0.43), however ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs 3.8%; p=0.03), including more instances of fatal intracranial bleeding and fewer of other types of fatal bleeding.

Of note, patients were excluded from SWEDEHEART registry if they underwent coronary-artery bypass grafting during the index hospitalisation. Therefore, this registry does not inform about real world data on bleeding related to this type of surgery in patients receiving ticagrelor.

In contrast, a subgroup of patients undergoing percutaneous revascularization and who received ticagrelor showed a more pronounced reduction in terms of death from all causes (adjusted HR 0.74 [95% CI 0.63 –0.86] vs. 0.93 [95% CI 0.78 –1.10] in non-PCI patients), meaning ACS patients managed invasively with PCI derived a 26% reduction in mortality.

The proportion of patients discharged on ticagrelor and clopidogrel over time is shown in Figure 1.

It is worth mentioning that the prescription of ticagrelor was rapidly implemented after it became available in Sweden (in the latter half of 2011). In the middle of 2012, the percentage of patients on ticagrelor had equalled that on clopidogrel. After that crossover, the growth of ticagrelor slowed and its prescription stabilised around 75% of ACS patients at the end of 2013.

Despite the progressive growth in the percentage of ticagrelor prescriptions, around 25 per cent of the included population still receive Clopidogrel. This may be due to formal contraindications of the drug, and is not expected to change over time.

Figure. Percentage of patients discharged on Ticagrelor and Clopidogrel over time

Figure 1: The proportion of patients discharged on ticagrelor and clopidogrel over time. [3]

Another point to be highlighted is that the benefit derived from treating patients with ticagrelor with respect to clopidogrel was similar between the main analysis at 24 months, and the sensitivity analysis at 12 months.

The maintenance of benefits after the first year of the index event has been a matter of discussion and the recent PEGASUS trial confirmed these favourable results, [5] further supporting how treatment length may conceivably be extended beyond the first year in selected patients with low bleeding risk.

In conclusion, the SWEDEHEART registry paints a comprehensive picture about the actual outcomes of ACS patients as they are currently treated under real-life conditions, and thus complements the data from randomised controlled Phase III trials. In future, data collection should be performed in a more standardised way with respect to endpoints, definitions, and time points, to enable further robust common analyses.

This cardionote was prepared by Dr Amelia Carro-Hevia (Spain) and published simultaneously on Cardio Debate and CardioMaster websites, as part of an ongoing collaboration between the two educational platforms. For more information on Cardiomaster please visit www.cardiomaster.net

REFERENCES:

  1. Roffi M, Patrono C, Collet JP, et al., 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37:267–315.
  2. Olivari Z, Steffenino G, Savonitto S, et al., The management of acute myocardial infarction in the cardiological intensive care units in Italy: the ‘BLITZ 4 Qualita’ campaign for performance measurement and quality improvement. Eur Heart J Acute Cardiovasc Care 2012;1:143–152.
  3. Sahlén A, Varenhorst C, Lagerqvist B, et al., Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry. Eur Heart J 2016; 37(44): 3335-3342.
  4. Wallentin L, Becker RC, Budaj A, PLATO Investigators, et al., Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045-57.
  5. Bonaca MP, Bhatt DL, Cohen M, et al., Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372: 1791-1800.