Ischemic stroke rates decrease with increased ticagrelor use after acute myocardial infarction in patients treated with percutaneous coronary intervention

Abstract

Aims

It is unknown whether dual antiplatelet therapy with ticagrelor instead of clopidogrel reduces the risk of ischaemic stroke in acute myocardial infarction patients that undergo percutaneous coronary intervention. This study investigated whether the introduction of dual antiplatelet therapy with ticagrelor was associated with reduced ischaemic stroke risk in a real-world population.

Methods and results

Patients with ischaemic stroke after acute myocardial infarction from 8 December 2009–31 December 2013 were identified using the Register for Information and Knowledge on Swedish Heart Intensive Care Admissions and the Swedish National Patient Register. The study period was divided into two similar periods using the date of the first prescription of ticagrelor as the cut-off. The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients during the first period (100% clopidogrel treatment) versus the second period (60.7% ticagrelor treatment) was assessed using Kaplan-Meier analysis. Variables associated with ischaemic stroke were identified using a multivariable Cox proportional hazards model. There were 686 ischaemic stroke events (2.0%) among 34931 percutaneous coronary intervention-treated acute myocardial infarction patients within one year, 366 (2.2%) during the first period and 320 (1.8%) during the second period (p = 0.004). The Cox model showed a 21% relative risk reduction in ischaemic stroke in the second period versus the first one (hazard ratio 0.79, 95% confidence interval, 0.68–0.92; p = 0.003). The independent predictors of increased stroke risk were older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and ST-segment elevation myocardial infarction.

Conclusion

The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients decreased after the introduction of ticagrelor in Sweden.

Keywords

Dual antiplatelet therapy ischemic stroke percutaneous coronary intervention acute myocardial infarction

Get full access to this article

View all access options for this article.

References

Brammas

Jakobsson

Ulvenstam

et al.

Mortality after ischemic stroke in patients with acute myocardial infarction: Predictors and trends over time in Sweden. Stroke 2013; 44: 3050–3055.

Kajermo

Ulvenstam

Modica

et al.

Incidence, trends, and predictors of ischemic stroke 30 days after an acute myocardial infarction. Stroke 2014; 45: 1324–1330.

Ulvenstam

Kajermo

Modica

et al.

Incidence, trends, and predictors of ischemic stroke 1 year after an acute myocardial infarction. Stroke 2014; 45: 3263–3268.

Valgimigli

Bueno

Byrne

et al.

2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2017; 0: 1–48.

The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial (TCiUAtPRET) Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502.

Wallentin

Becker

Budaj

et al.

Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–1057.

James S. SCAAR Annual Report 2016, http://www.ucr.uu.se/swedeheart/arsrapport-2017/aeldre-arsrapporter-older-reports/arsrapport-2016/swedeheart-2016-scaar (2016, accessed 15 November 2017).

Cannon CP, Harrington RA, James S, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): A randomised double-blind study. Lancet 2010; 375: 283–293.

Angeras

Hasvold

Thuresson

et al.

Treatment pattern of contemporary dual antiplatelet therapies after acute coronary syndrome: A Swedish nationwide population-based cohort study. Scand Cardiovasc J 2016; 50: 99–107.

10.

D'Ascenzo

Iannaccone

Saint-Hilary

et al.

Impact of design of coronary stents and length of dual antiplatelet therapies on ischaemic and bleeding events: A network meta-analysis of 64 randomized controlled trials and 102 735 patients. Eur Heart J 2017; 38: 3160–3172.

11.

Lettino

Leonardi

De Maria

et al.

Antiplatelet and antithrombotic treatment for secondary prevention in ischaemic heart disease. Eur J Prev Cardiol 2017; 24: S61–S70.

12.

Stenestrand

Wallentin

. for the Swedish Register of Cardiac Intensive C. Early statin treatment following acute myocardial infarction and 1-year survival. JAMA 2001; 285: 430–436.

13.

Janszky

Ahnve

Ljung

et al.

Daylight saving time shifts and incidence of acute myocardial infarction–Swedish Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA). Sleep Med 2012; 13: 237–242.

14.

Jernberg

Attebring

Hambraeus

et al.

The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Heart 2010; 96: 1617–1621.

15.

Ludvigsson

Andersson

Ekbom

et al.

External review and validation of the Swedish National Inpatient Register. BMC Public Health 2011; 11: 450–450.

16.

Koster

Asplund

Johansson

et al.

Refinement of Swedish administrative registers to monitor stroke events on the national level. Neuroepidemiology 2013; 40: 240–246.

17.

Lindholm

Varenhorst

Cannon

et al.

Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: Results from the PLATO trial. Eur Heart J 2014; 35: 2083–2093.

18.

Bonaca

Bhatt

Cohen

et al.

Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372: 1791–1800.

19.

Witt

Ballman

Brown

Jr et al.

The incidence of stroke after myocardial infarction: A meta-analysis. Am J Med 2006; 119: 354.e1–9.

20.

Budaj

Flasinska

Gore

et al.

Magnitude of and risk factors for in-hospital and postdischarge stroke in patients with acute coronary syndromes: Findings from a Global Registry of Acute Coronary Events. Circulation 2005; 111: 3242–3247.

21.

Rathore SS, Berger AK, Weinfurt KP, Schulman KA, Oetgen WJ, Gersh BJ, et al. Acute myocardial infarction complicated by atrial fibrillation in the elderly. prevalence and outcomes. Circulation 2000; 101: 969–74.

22.

Crenshaw

Ward

Granger

et al.

Atrial fibrillation in the setting of acute myocardial infarction: The GUSTO-I experience. J Am Coll Cardiol 1997; 30: 406–413.

23.

Hachet

Guenancia

Stamboul

et al.

Frequency and predictors of stroke after acute myocardial infarction: Specific aspects of in-hospital and postdischarge events. Stroke 2014; 45: 3514–3520.

24.

Mooe

Eriksson

Stegmayr

. Ischemic stroke after acute myocardial infarction: A population-based study. Stroke 1997; 28: 762–767.

25.

Kamel

Healey

. Cardioembolic stroke. Circ Res 2017; 120: 514–526.

26.

Mooe

. Risk, mechanisms and prevention of stroke after an acute myocardial infarction. Expert Rev Neurother 2002; 2: 177–186.

27.

Joshi

Toor

Shah

et al.

Systemic atherosclerotic inflammation following acute myocardial infarction: Myocardial infarction begets myocardial infarction. J Am Heart Assoc 2015; 4: e001956–e001956.

28.

Kim

Lee

Kim

et al.

Concurrent carotid inflammation in acute coronary syndrome as assessed by (18)F-FDG PET/CT: A possible mechanistic link for ischemic stroke. J Stroke Cerebrovasc Dis 2015; 24: 2547–2554.

29.

Dufouil

Beiser

McLure

et al.

Revised Framingham stroke risk profile to reflect temporal trends. Circulation 2017; 135: 1145–1159.

30.

Socialstyrelsen. Täckningsgrader 2016 Jämförelser mellan nationella kvalitetsregister och hälsodataregistren. Stockholm: Socialstyrelsen. http://www.socialstyrelsen.se/publikationer2017/2017-1-23.