Routine invasive strategy for NSTEMI ACS showed no mortality benefit 10 years out

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Attenuation might be due to practice changes

The authors… find that the all-cause mortality reduction of 24% seen at 5 years has slowly dissipated by 10 years, with no statistical significance. The authors further stratify the results by the post-discharge GRACE score and find no clear treatment effect by low-, intermediate-, or high-risk categories. They also perform a multivariable model that identifies age, prior myocardial infarction or heart failure, and extent of coronary disease as important predictors of long-term mortality, but not the randomization strategy.

What can practicing physicians take from these findings? It seems most likely that the significant treatment effect from the initial study, the widespread clinical presentation of the trial findings, and guideline recommendations caused clinical practice to shift toward more routine invasive care. This is what we would hope happens with an active quality cycle in which findings are incorporated into clinical practice.

These findings of RITA-3 can therefore be interpreted as an important milestone of understanding the effect of an early invasive strategy on long-term outcomes. As such, the trial suggests that the benefit observed initially may not be translated into a longer benefit. How much of this attenuation can be ascribed to a change in practice pattern remains unclear. However, we should be heartened by the fact that physicians may be using the latest clinical trial data to improve the care for their patients with acute coronary syndromes, and therefore, our ability to interpret late outcomes may be heavily affected by the improving physicians’ performance around guidelines and the optimal care for patients with ACS. This is a very positive message indeed if you are a patient, but it makes it much harder if you are a researcher or guidelines writer in the field of cardiology.

Dr. Manesh R. Patel and Dr. E. Magnus Ohman are with the Division of Cardiovascular Medicine at Duke Heart Center in Durham, N.C. Dr. Patel reported having no relevant financial disclosures, while Dr. Ohman reported relationships with Daiichi-Sankyo, Eli Lilly & Co., Gilead Sciences, Janssen Pharmaceuticals, Abiomed, AstraZeneca, Biotie, Boehringer Ingelheim, Faculty Connection, Merck, Stealth Peptides, The Medicines Company, and WebMD. These comments are taken from their accompanying editorial (J. Am. Coll. Cardiol. 2015; 66: 521-3 [doi: 10.1016/j.jacc.2015.06.024]).




Ten-year mortality rates in the RITA-3 trial were similar regardless of whether patients with non-ST-segment elevation acute coronary syndrome underwent invasive treatment routinely or selectively, researchers reported July 27 in the Journal of the American College of Cardiology.

Prospective trials therefore will need to keep exploring which patients benefit from routine early invasive treatment, Dr. Robert A. Henderson at Nottingham University Hospitals in the United Kingdom, and his associates, wrote.

The RITA-3 (Third Randomised Intervention Treatment of Angina) trial randomized 1,810 patients with non-ST segment elevation acute coronary syndrome (NSTEMI ACS) to either routine or selective invasive treatment. Routine treatment consisted of coronary arteriography within 72 hours of the index episode of myocardial ischemia, with myocardial revascularization when clinically indicated. The selective strategy centered on antiangina medications. Patients only underwent coronary arteriography if they experienced recurrent ischemic pain at rest or during minimal exertion, with transient or persistent electrocardiographic ischemia (J. Am. Coll. Cardiol. 2015; 66: 511-20 [10.1016/j.jacc.2015.05.051]).

At 5 years, routine invasive treatment had a lower odds of cardiovascular death and myocardial infarction than selective invasive treatment, as well as a lower odds of all-cause mortality, the researchers previously reported (Lancet. 2005; 366: 914-20).

But at 10 years, all-cause mortality was 25% for both groups, and rates of cardiovascular death were 15% and 16% for routine versus selective invasive strategies (P = 0.65), they wrote. Age, history of previous myocardial infarction, heart failure, smoking, diabetes, heart rate, and ST-segment depression all predicted 10-year mortality in the multivariable analysis, but randomization strategy did not, they added.

When the researchers stratified patients based on Global Registry of Acute Coronary Events (GRACE) scores, death rates ranged from 14% for low-risk patients to 56% for high-risk patients, but did not vary by treatment strategy. The results highlight the need for more trials of intervention strategies for NSTEMI ACS, the researchers concluded.

The British Heart Foundation funded the RITA-3 trial and received relevant support from Aventis Pharma. One of the study co-authors reported receiving grant support from The Medicines Company, and the authors reported having no relevant financial disclosures.

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