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Acute Coronary Syndromes: The Way Forward From Mechanisms to Precision Treatment.

ABSTRACT: Well into the 21st century, we still triage acute myocardial infarction on the basis of the presence or absence of ST-segment elevation, a century-old technology. Meanwhile, we have learned a great deal about the pathophysiology and mechanisms of acute coronary syndromes (ACS) at the clinical, pathological, cellular, and molecular levels. Contemporary imaging studies have shed new light on the mechanisms of ACS. This review discusses these advances and their implications for clinical management of the ACS for the future. Plaque rupture has dominated our thinking about ACS pathophysiology for decades. However, current evidence suggests that a sole focus on plaque rupture vastly oversimplifies this complex collection of diseases and obscures other mechanisms that may mandate different management strategies. We propose segmenting coronary artery thrombosis caused by plaque rupture into cases with or without signs of concomitant inflammation. This distinction may have substantial therapeutic implications as direct anti-inflammatory interventions for atherosclerosis emerge. Coronary artery thrombosis caused by plaque erosion may be on the rise in an era of intense lipid lowering. Identification of patients with of ACS resulting from erosion may permit a less invasive approach to management than the current standard of care. We also now recognize ACS that occur without apparent epicardial coronary artery thrombus or stenosis. Such events may arise from spasm, microvascular disease, or other pathways. Emerging management strategies may likewise apply selectively to this category of ACS. We advocate this more mechanistic approach to the categorization of ACS to provide a framework for future tailoring, triage, and therapy for patients in a more personalized and precise manner.

SUBMITTER: Crea F

PROVIDER: S-EPMC5679086 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Acute Coronary Syndromes: The Way Forward From Mechanisms to Precision Treatment.

Crea Filippo F Libby Peter P

Circulation 20170901 12

Well into the 21st century, we still triage acute myocardial infarction on the basis of the presence or absence of ST-segment elevation, a century-old technology. Meanwhile, we have learned a great deal about the pathophysiology and mechanisms of acute coronary syndromes (ACS) at the clinical, pathological, cellular, and molecular levels. Contemporary imaging studies have shed new light on the mechanisms of ACS. This review discusses these advances and their implications for clinical management ...[more]

PMID: 28923905

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Project description:BackgroundThe Coronary Psychosocial Evaluation Studies trial demonstrated promising results for enhanced depression treatment to reduce cardiovascular risk of patients with acute coronary syndrome and comorbid depression, but the long-term effectiveness of this intervention is unclear.MethodsA total of 157 participants with persistent depression after hospitalization for acute coronary syndromes were enrolled in the Coronary Psychosocial Evaluation Studies trial. A total of 80 participants were allocated to 6 months of enhanced depression treatment, and 77 participants were allocated to usual care. We report on an additional 12 months of observational follow-up for the composite outcome of death or first hospitalization for myocardial infarction or unstable angina.ResultsAlthough the intervention was previously shown to have favorable cardiovascular effects during the treatment period, we observed a significant time-by-treatment group interaction during extended follow-up (P = .008). Specifically, during the 6-month treatment period, death or hospitalization for myocardial infarction/unstable angina occurred in 3 participants (4%) in the treatment group compared with 11 participants (14%) in the usual care group (hazard ratio, 0.25; 95% confidence interval, 0.07-0.90; P = .03). In contrast, during 12 months of additional observational follow-up, 11 participants (14%) in the treatment group experienced the composite outcome of death or hospitalization for myocardial infarction/unstable angina compared with 3 participants (4%) in the usual care group (hazard ratio, 2.91; 95% confidence interval, 0.80-10.56; P = .10).ConclusionsEnhanced depression treatment was associated with a reduced risk of death or hospitalization for myocardial infarction/unstable angina during active treatment, but this effect did not persist after treatment ceased. Future research is needed to confirm our findings and to determine the optimal duration of depression treatment in patients with depression after acute coronary syndromes.

Project description:Conflicting information exists about whether sex differences modulate short-term mortality following acute coronary syndromes (ACS).To investigate the relationship between sex and 30-day mortality in ACS, and to determine whether this relationship was modified by clinical syndrome or coronary anatomy using a large database across the spectrum of ACS and adjusting for potentially confounding clinical covariates.A convenience sample of patients pooled from 11 independent, international, randomized ACS clinical trials between 1993 and 2006 whose databases are maintained at the Duke Clinical Research Institute, Durham, North Carolina. Of 136 247 patients, 38 048 (28%) were women; 102 004 (26% women) with ST-segment elevation myocardial infarction (STEMI), 14 466 (29% women) with non-STEMI (NSTEMI), and 19 777 (40% women) with unstable angina.Thirty-day mortality following ACS.Thirty-day mortality was 9.6% in women and 5.3% in men (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.83-2.00). After multivariable adjustment, mortality was not significantly different between women and men (adjusted OR, 1.06; 95% CI, 0.99-1.15). A significant sex by type of ACS interaction was demonstrated (P < .001). In STEMI, 30-day mortality was higher among women (adjusted OR, 1.15; 95% CI, 1.06-1.24), whereas in NSTEMI (adjusted OR, 0.77; 95% CI, 0.63-0.95) and unstable angina, mortality was lower among women (adjusted OR, 0.55; 95% CI, 0.43-0.70). In a cohort of 35 128 patients with angiographic data, women more often had nonobstructive (15% vs 8%) and less often had 2-vessel (25% vs 28%) and 3-vessel (23% vs 26%) coronary disease, regardless of ACS type. After additional adjustment for angiographic disease severity, 30-day mortality among women was not significantly different than men, regardless of ACS type. The relationship between sex and 30-day mortality was similar across the levels of angiographic disease severity (P for interaction = .70).Sex-based differences existed in 30-day mortality among patients with ACS and vary depending on clinical presentation. However, these differences appear to be largely explained by clinical differences at presentation and severity of angiographically documented disease.

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Acute Coronary Syndromes: The Way Forward From Mechanisms to Precision Treatment.

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Acute Coronary Syndromes: The Way Forward From Mechanisms to Precision Treatment.

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