Author + information
- Received October 15, 2008
- Revision received December 19, 2008
- Accepted December 22, 2008
- Published online April 21, 2009.
- Benjamin M. Scirica, MD, MPH*,†,* (, )
- David A. Morrow, MD, MPH*,†,
- Andrzej Budaj, MD, PhD‡,
- Anthony J. Dalby, MD§,
- Satishkumar Mohanavelu, MS*,
- Jie Qin, MS*,
- Julian Aroesty, MD*,
- Chester M. Hedgepeth, MD, PhD†,
- Peter H. Stone, MD† and
- Eugene Braunwald, MD*,†
- ↵*Reprint requests and correspondence:
Dr. Benjamin M. Scirica, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115
Objectives The purpose of this study was to assess the relationship between ischemia detected on continuous electrocardiographic (cECG) recording and cardiovascular outcomes after acute coronary syndrome (ACS).
Background The small size of prior studies evaluating cECG prevented full evaluation of the risk associated with ischemia across subpopulations and compared with other methods of risk stratification. Ranolazine, a new antianginal agent, reduces ischemic symptoms in patients with chronic angina and after ACS but the anti-ischemic effect, as detected by cECG, is not known.
Methods In all, 6,560 patients hospitalized with non–ST-segment elevation ACS were randomly assigned to ranolazine or placebo in the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndrome–Thrombolysis In Myocardial Infarction 36) trial. The cECG was performed for 7 days after randomization. Outcomes were followed for a median of 348 days. Clinical events that occurred during cECG recording were excluded from analysis.
Results A total of 6,355 (97%) patients had cECG recordings evaluable for ischemia analysis. Patients with ≥1 episode of ischemia on cECG (n = 1,271, 20%) were at increased risk of cardiovascular death (7.7% vs. 2.7%, p < 0.001), MI (9.4% vs. 5.0%, p < 0.001), and recurrent ischemia (17.5% vs. 12.3%, p < 0.001). The relationship with cardiovascular death was independent of baseline characteristics or elevated biomarkers (adjusted hazard ratio: 2.46, p < 0.001). Ischemia on cECG was associated with significantly worse outcomes in several subgroups. Ranolazine did not reduce the rate of ischemia detected on cECG (19.9% vs. 21.0%, hazard ratio: 0.93, p = 0.21).
Conclusions In more than 6,300 patients with ACS, ischemia detected on cECG occurred frequently and was strongly and independently associated with poor cardiovascular outcomes, including cardiovascular death. Continuous ECG monitoring to detect ischemia after ACS may help to identify patients at increased risk. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes [MERLIN]; NCT00099788)
Continuing Medical Education (CME) is available for this article. Go to http://cme.jaccjournals.orgto participate.
The MERLIN-TIMI 36 study was supported by CV Therapeutics. The TIMI Study Group reports receiving significant research grant support from Accumetrics, Amgen, AstraZeneca, Bayer Healthcare, Beckman Coulter, Biosite, Bristol-Myers Squibb, CV Therapeutics, Eli Lilly, GlaxoSmithKline, Inotek Pharmaceuticals, Integrated Therapeutics, Merck & Co., Merck-Schering Plough Joint Venture, Millennium Pharmaceuticals, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, and Schering-Plough. Dr. Scirica receives honoraria for consulting and educational presentations from CV Therapeutics, and is supported in part by an unrestricted research grant from Michael Lerner. Dr. Morrow receives honoraria for educational presentations from CV Therapeutics and Sanofi-Aventis, serves as a consultant for GlaxoSmithKline and Sanofi-Aventis, and is on the advisory board for Genentech. Dr. Budaj receives honoraria from CV Therapeutics, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, and Sanofi-Aventis, and serves as a consultant to GlaxoSmithKline and Sanofi-Aventis. Dr. Aroesty serves as a consultant to Fibrogen, which has no commercial products and is conducting no research that could bear any relationship to this paper. Dr. Stone receives a research grant from CV Therapeutics. Dr. Braunwald receives honoraria from and serves as a consultant to AstraZeneca, Bayer AG, CV Therapeutics, Daichii Sankyo, Merck, Pfizer, and Schering-Plough.
- Received October 15, 2008.
- Revision received December 19, 2008.
- Accepted December 22, 2008.
- American College of Cardiology Foundation