Christopher P. Cannon

Background—: Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain. Methods and Results—: In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39–5.79; P =0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P =0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07–28.20; P =0.01), and then decreasing over time such that the relationship was no longer significant by ≈5 months after ACS. Conclusions—: NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event. Clinical Trial Registration—: http://www.clinicaltrials.gov . Unique identifier: NCT00391872.

Background—: We sought to evaluate the effect of potent platelet inhibition after acute coronary syndrome on total (ie, first and recurrent) occurrences of any of the primary outcome events (eg, cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia, transient ischemic attacks, and arterial thrombotic events. Methods and Results—: In the PLATelet inhibition and patient Outcomes (PLATO) study, 18 624 patients presenting with acute coronary syndromes randomly received ticagrelor (n=9333) or clopidogrel (n=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model, and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary end point events versus 1225 for patients on clopidogrel (rate ratio, 0.86; 95% confidence interval, 0.79–0.93; P =0.003). The number of additional events was numerically lower for ticagrelor (189 versus 205; P =0.40), resulting in a hazard for time to second event/death of 0.80 (95% confidence interval, 0.70–0.90; P P P =0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% confidence interval, 0.75–0.91; P P =0.96 and 0.38, respectively). Conclusions—: In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared with clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov/ . Unique identifier: NCT00391872.

Results from different types of clinical research studies provide different types of evidence for evaluating the effects of a new drug or intervention. For this reason, it is important to recognize this phenomenon during reporting and to choose appropriate language to match the type of study that was done, because this can become critical to the interpretation and application of the results in clinical practice. In this article, we aim to highlight this issue through a series of examples and provide some guidance on what the appropriate language for different types of studies should be.This editorial review was cowritten and developed as an expanded background piece to accompany the statement by the HEART Group journal editors, which is being published simultaneously with this article.The authors have no funding, financial relationships, or conflicts of interest to disclose.

A morning peak in ST-segment elevation myocardial infarction (STEMI) has been described. The authors explored the relationship between variation of symptom onset, patient characteristics, and outcomes in two worldwide fibrinolytic trials. A total of 35 492 patients with STEMI were grouped into 8-h intervals by time of symptom onset: early (06:00 to 13:59 h), late-day (14:00 to 21:59 h), overnight (22:00 to 05:59 h). The authors correlated timing with patient characteristics and outcomes (adjusted for thrombolysis in myocardial infarction [TIMI] risk score) first in InTIME II-TIMI 17 trial (N = 15 031), and confirmed in the ExTRACT-TIMI 25 trial (N = 20 461). Timing was similar in the derivation (early 49%, late-day 30%, and overnight 21%; p < .001) and validation set (48%, 31%, and 21%, respectively; p < .001). Some patient characteristics consistently varied with time of symptom onset. Patients in the early cohort were older with poorer renal function. The late-day group had more smokers with higher initial heart rate and systolic blood pressure. Those with overnight symptom onset had higher rates of obesity, prior myocardial infarction, and treatment delays. Prior use of aspirin and beta-blockers was also highest in the overnight group. Relative to the early cohort, adjusted mortality was higher with late-day onset (derivation odds ratio [OR]: 1.19, p = .04; validation OR: 1.18, p = .01), but there was no excess in mortality overnight compared with early (derivation OR: .97, p = .72; validation OR: 1.01, p = .90). Composite endpoints followed similar patterns. This study indicates that circadian patterns in onset of STEMI continue to exist with patient characteristics differing by time of day. Despite a potential physiologic resistance to morning thrombolysis, outcomes were best in the early cohort, intermediate overnight, and worst with late-day symptom onset. Efforts to reduce smoking and improve control of blood pressure could reduce the number of patients with late-day onset of STEMI who experience the worst outcomes. (Author correspondence: owen@mogabgab. com )

The vascular location of an enzyme accounts for the cardiovascular hazards associated with its inhibition.

This editorial refers to ‘Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial’†, by M.E. Visser et al., on page 1142