European Heart Journal Advance Access published online on November 10, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp457
Chronic nitrate therapy is associated with different presentation and evolution of acute coronary syndromes: insights from 52 693 patients in the Global Registry of Acute Coronary Events
1 Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy
2 Division of Internal Medicine, University of Perugia School of Medicine, Perugia, Italy
3 Center for Outcomes Research, UMASS Medical School, Worcester, MA, USA
4 Department of Cardiology, Hospital Universitario La Paz, Madrid, Spain
5 Department of Cardiology, Hoag Memorial Hospital Presbyterian, Newport Beach, CA, USA
6 Division of Medical and Radiological Sciences, Cardiovascular Research, The University of Edinburgh, Edinburgh, UK
Received 10 January 2009; revised 25 August 2009; accepted 17 September 2009 * Corresponding author. Cardiologia, Ospedale Silvestrini, S. Andrea delle Fratte, 06156 Perugia, Italy. Tel: +39 075 527 1509, Fax: +39 075 527 1244, Email: giuseppe.ambrosio{at}ospedale.perugia.it
Aims: Brief episode(s) of ischaemia may increase cardiac tolerance to a subsequent major ischaemic insult (‘preconditioning’). Nitrates can pharmacologically mimic ischaemic preconditioning in animals. In this study, we investigated whether antecedent nitrate therapy affords protection toward acute ischaemic events using data from the Global Registry of Acute Coronary Events.
Methods and results: The dataset comprised 52 693 patients from 123 centres in 14 countries: 42 138 (80%) were nitrate-naïve and 10 555 (20%) were on chronic nitrates at admission. In nitrate-naïve patients, admission diagnosis was ST-segment elevation myocardial infarction (STEMI) in 41%, whereas 59% presented with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). In contrast, only 18% nitrate users showed STEMI, whereas 82% presented with NSTE-ACS. Thus, among nitrate users clinical presentation was tilted toward NSTE-ACS by more than four-fold, STEMI occurring in less than one of five patients (P < 0.0001). After adjustment (age, sex, medical history, prior therapy, revascularization, previous angina), chronic nitrate use remained independent predictor of NSTE-ACS (OR 1.36; 95% CI 1.26–1.46; P < 0.0001). Furthermore, regardless of presentation, within both STEMI and NSTEMI populations, antecedent nitrate use was associated with significantly lower levels of CK-MB and troponin (P < 0.0001 for all).
Conclusion: In this large multinational registry, chronic nitrate use was associated with a shift away from STEMI in favour of NSTE-ACS and with less release of markers of cardiac necrosis. These findings suggest that in nitrate users acute coronary events may develop to a smaller extent. Randomized, placebo-controlled trials are warranted to establish whether nitrate therapy may pharmacologically precondition the heart toward ischaemic episodes.
Key Words: Ischaemia • Acute coronary syndromes • Preconditioning • Nitrates
Presented in part at the European Society of Cardiology Congress, Stockholm, Sweden, 2005.