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Background: Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.Objectives: This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time.Methods: This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440).Results: Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018).Conclusion: In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294). [ABSTRACT FROM AUTHOR]

Background: Smoking is a well-documented risk for acute ST-segment elevation myocardial infarction (STEMI). The differential effect between sexes has yet to be quantified.Objectives: The purpose of this study was to differentiate the effect of smoking on increased risk of STEMI between sexes.Methods: For this retrospective ecological cohort study, all patients at a U.K. tertiary cardiothoracic center who presented between 2009 and 2014 with acute STEMI were combined with population data to generate incidence rates of STEMI. Age-standardized incidence rate ratios (IRRs) using the Poisson distribution were calculated comparing STEMI rates between smokers and nonsmokers stratified by sex and 3 age groups (18 to 49, 50 to 64, and >65 years).Results: A total of 3,343 patients presented over 5,639,328 person-years. Peak STEMI rate for current smokers was in the 70 to 79 years age range for women (235 per 100,000 patient-years) and 50 to 59 years (425 per 100,000 patient-years) in men. Smoking was associated with a significantly greater increase in STEMI rate for women than men (IRR: 6.62; 95% confidence interval [CI]: 5.98 to 7.31, vs. 4.40; 95% CI: 4.15 to 4.67). The greatest increased risk was in women age 18 to 49 (IRR: 13.22; 95% CI: 10.33 to 16.66, vs. 8.60; 95% CI: 7.70 to 9.59 in men). The greatest risk difference was in the age 50 to 64 years group, with IRR of 9.66 (95% CI: 8.30 to 11.18) in women and 4.47 (95% CI: 4.10 to 4.86) in men.Conclusions: This study quantifies the differential effect of smoking between sexes, with women having a significantly increased risk of STEMI than men. This information encourages continued efforts to prevent smoking uptake and promote cessation. [ABSTRACT FROM AUTHOR]