Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: A pre-specified subset analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation (COURAGE) trial.

OBJECTIVES: To determine whether sex-based differences exist in clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in patients with stable coronary artery disease. BACKGROUND: A prior pre-specified unadjusted analysis from COURAGE showed that women randomized to PCI had a lower rate of death or myocardial infarction during a median 4.6-year follow-up with a trend for interaction with respect to sex. METHODS: We analyzed outcomes in 338 women (15%) and 1949 men (85%) randomized to PCI plus OMT versus OMT alone after adjustment for relevant baseline characteristics. RESULTS: There was no difference in treatment effect by sex for the primary end point (death or myocardial infarction; HR, 0.89; 95% CI, 0.77-1.03 for women and HR, 1.02, 95% CI 0.96-1.10 for men; P for interaction = .07). Although the event rate was low, a trend for interaction by sex was nonetheless noted for hospitalization for heart failure, with only women, but not men, assigned to PCI experiencing significantly fewer events as compared to their counterparts receiving OMT alone (HR, 0.59; 95% CI, 0.40-0.84, P < .001 for women and HR, 0.86; 95% CI, 0.74-1.01, P = .47 for men; P for interaction = .02). Both sexes randomized to PCI experienced significantly reduced need for subsequent revascularization (HR, 0.72; 95% CI, 0.62-0.83, P < .001 for women; HR, 0.84; 95% CI, 0.79-0.89, P < .001 for men; P for interaction = .02) with evidence of a sex-based differential treatment effect. CONCLUSION: In this adjusted analysis of the COURAGE trial, there were no significant differences in treatment effect on major outcomes between men and women. However, women assigned to PCI demonstrated a greater benefit as compared to men, with a reduction in heart failure hospitalization and need for future revascularization. These exploratory observations require further prospective study.

Use of prehospital electrocardiograms for the treatment of patients with ST-segment elevation myocardial infarction.

Use of prehospital electrocardiograms (ECG) by emergency medical personnel may reduce door-to-balloon (DTB) time in patients with ST-segment elevation myocardial infarction (STEMI) referred for urgent percutaneous coronary intervention (PCI). A 79-year-old female awoke from sleep with severe substernal chest pain and called 911 for assistance. The patient was initially evaluated by advanced life support paramedics who performed a 12-lead ECG at the patient's home. The ECG, which demonstrated an acute inferior STEMI, was transferred using a novel, web-based system to Hartford Hospital's Emergency Department. As a result of prehospital communication, the on-call catheterization team was mobilized prior to the patient's arrival. The patient underwent successful PCI of an occluded right coronary artery with a DTB time of 67 minutes and was subsequently discharged four days later. Use of prehospital electrocardiography combined with early catheterization laboratory mobilization allowed for timely STEMI reperfusion according to national guidelines, despite "off-hour" presentation.

Long-term efficacy and safety of sirolimus-eluting vs bare-metal stents.

BACKGROUND: Although previous studies have documented persistent clinical benefit of sirolimus-eluting stents (SES)in reducing the need for target vessel revascularization without an increase in myocardial infarction (MI) or mortality, the long-term safety and efficacy of CYPHER stent use in routine clinical practice, including off-label stent implantation, remains uncertain. METHODS: We compared long-term clinical outcomes in 2,550 patients treated with one or more SES with 1,022 patients treated with one or more bare metal or heparin-coated stents (BMS). The study groups included 1,058 SES patients (41.5%) and 488 BMS patients (47.7%) with off-label indications. A propensity-score method was utilized to adjust for differences in baseline characteristics. Patients were followed for up to five years for the occurrence of all-cause mortality, MI and repeat target vessel revascularization. RESULTS: Compared to BMS patients, SES patients demonstrated significantly improved event-free survival with respect to all-cause mortality (RR, 1.39; 95% CI, 1.07 to 1.80, P = 0.014) and repeat target vessel revascularization (RR, 2.72; 95% CI, 1.99 to 3.73, P < 0.001), with no significant difference in the incidence of cumulative MI. A landmark analysis, examining composite adverse events occurring six months after stent implantation in the two study groups, demonstrated no increased late hazard associated with SES use (relative risk, 1.08; 95% CI, 0.80 to 1.46). CONCLUSIONS: Use of SES in routine clinical practice, including off-label indications, is associated with improved long-term mortality, reduced need for repeat target vessel revascularization and no increase in MI compared to BMS.

Changes in muscle strength in individuals with statin-induced myopathy: A summary of 3 investigations.

BACKGROUND: There are inconsistent findings regarding muscular weakness in individuals with statin-induced myalgia. OBJECTIVE: We used rigorous muscle testing to compare findings from 3 investigations in 3 different study populations to determine if statin myalgia is associated with measurable weakness. METHODS: In all 3 studies, we measured maximal isometric handgrip strength, resting respiratory exchange ratio (RER), and knee extensor isometric and isokinetic force. In 2 of the 3 studies, elbow flexor isometric and isokinetic force and knee endurance fatigue index were also assessed. Knee extensor and elbow flexor measurements were obtained using an isokinetic dynamometer. Resting RER was measured using a metabolic breath-by-breath collection method. Measurement outcomes were compared on vs off drug. RESULTS: In study 1, 18 participants fit the criteria for statin myalgia. Participants taking atorvastatin 80 mg daily had significantly lower muscle strength in 5 (P < .05) of 14 measured variables. Participants on placebo (N = 10) with myalgia had significantly lower muscle strength in 4 (P < .05) of 14 measured variables. In study 2, 18 participants tested positive for statin-induced myalgia when receiving simvastatin 20 mg daily and displayed no significant muscle strength changes (all P > .05). In study 3, 11 patients with statin-induced myalgia completed the study and had a significant decrease in 2 (P < .05) of 10 leg muscle strength variables. In all 3 studies, no significant changes were shown for handgrip strength or RER (all P > .05). CONCLUSION: Our results indicate that after a short-term treatment with statin therapy, a rigorous muscle strength protocol does not show decrements of muscle strength in subjects with statin myalgia. Short-term treatment with statin therapy is not common in clinical practice. Thus, future studies should examine the effects of prolonged statin therapy on muscle strength.

The effect of compression socks worn during a marathon on hemostatic balance.

INTRODUCTION: Marathon running evokes parallel increases in markers of coagulation and fibrinolysis (i.e. hemostatic activation) immediately following strenuous, endurance exercise such that hemostatic balance is maintained. However, other factors incident to marathon running (i.e. dehydration, travel) may disproportionately activate the coagulatory system, increasing blood clot risk after an endurance event in otherwise healthy individuals. We investigated the effect of compression socks on exercise-induced hemostatic activation and balance in endurance athletes running the 2013 Hartford Marathon. METHODS: Adults (n = 20) were divided into compression sock (SOCK; n = 10) and control (CONTROL; n = 10) groups. Age, anthropometrics, vital signs, training mileage and finishing time were collected. Venous blood samples were collected 1 day before, immediately after and 1 day following the marathon for analysis of coagulatory (i.e. thrombin-antithrombin complex [TAT] and D-dimer) and fibrinolytic (i.e. tissue plasminogen activator [t-PA]) factors. RESULTS: Plasma D-dimer, TAT and t-PA did not differ between groups at baseline (p > 0.16). There were no significant group · time interactions (all p ≥ 0.17), however, average t-PA was lower in SOCK (8.9 ± 0.7 ng/mL) than CONTROL (11.2 ± 0.7 ng/mL) (p = 0.04). Average TAT also tended to be lower in SOCK (2.8 ± 0.2 µg/L) than CONTROL (3.4 ± 0.2 µg/L) (p = 0.07). CONCLUSIONS: Our results suggest that overall hemostatic activation (both coagulation and fibrinolysis) following a marathon tended to be lower with compression socks. Thus, compression socks do not adversely influence markers of hemostasis, appear safe for overall use in runners and may reduce exercise-associated hemostatic activation in individuals at risk for deep vein thrombosis.

Influence of chronic exercise on carotid atherosclerosis in marathon runners.

OBJECTIVES: The effect of habitual, high-intensity exercise training on the progression of atherosclerosis is unclear. We assessed indices of vascular health (central systolic blood pressure (SBP) and arterial stiffness as well as carotid intima-medial thickness (cIMT)) in addition to cardiovascular risk factors of trained runners versus their untrained spouses or partners to evaluate the impact of exercise on the development of carotid atherosclerosis. SETTING: field study at Boston Marathon. PARTICIPANTS: 42 qualifiers (mean age±SD: 46±13 years, 21 women) for the 2012 Boston Marathon and their sedentary domestic controls (46±12 years, n=21 women). OUTCOMES: We measured medical and running history, vital signs, anthropometrics, blood lipids, C reactive protein (CRP), 10 years Framingham risk, central arterial stiffness and SBP and cIMT. RESULTS: Multiple cardiovascular risk factors, including CRP, non-high-density lipoprotein cholesterol, triglycerides, heart rate, body weight and body mass index (all p<0.05), were reduced in the runners. The left and right cIMT, as well as central SBP, were not different between the two groups (all p>0.31) and were associated with age (all r≥0.41; p<0.01) and Framingham risk score (all r≥0.44; p<0.01) independent of exercise group (all p>0.08 for interactions). The amplification of the central pressure waveform (augmentation pressure at heart rate 75 bpm) was also not different between the two groups (p=0.07) but was related to age (p<0.01) and group (p=0.02) in a multiple linear regression model. CONCLUSIONS: Habitual endurance exercise improves the cardiovascular risk profile, but does not reduce the magnitude of carotid atherosclerosis associated with age and cardiovascular risk factors.

Comparison of outcomes and safety of "facilitated" versus primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction.

Recent studies have documented that use of "facilitated" percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) may be harmful. In-hospital outcomes in 1,553 consecutive patients with STEMI without cardiogenic shock who underwent PCI at a single tertiary center within 6 hours of presentation were analyzed. The study group included 767 patients who underwent primary PCI who initially presented to the tertiary center and were triaged for emergent PCI and 786 patients who underwent facilitated PCI who were pretreated at a community hospital with a glycoprotein IIb/IIIa platelet inhibitor and/or intravenous thrombolytic therapy before transfer for catheter-based therapy. Compared with patients who underwent primary PCI, the facilitated PCI group had longer door-to-balloon times (162 +/- 57 vs 113 +/- 61 minutes), higher baseline infarct-vessel TIMI 3 flow rates (52.8% vs 25.4%; p <0.001), and no increase in major adverse in-hospital outcomes. In patients treated with door-to-balloon times >90 and < or =150 minutes, patients who underwent facilitated PCI had fewer composite major adverse clinical events (combined mortality, recurrent myocardial infarction, emergent repeated PCI, hemorrhagic and nonhemorrhagic stroke, and nonintracranial TIMI major bleeding) compared with patients who underwent primary PCI (relative risk 0.50, 95% confidence interval 0.26 to 0.96, p = 0.034). In conclusion, facilitated PCI can be safely used to increase pharmacologic reperfusion before catheter-based therapy in patients with STEMI without an increase in clinical hazard and with fewer major adverse clinical events in patients treated with door-to-balloon times >90 and < or =150 minutes.