Karin S. Coyne

A randomized trial comparing primary angioplasty with a strategy of short-acting thrombolysis and immediate planned rescue angioplasty in acute myocardial infarction: the PACT trial ☆

OBJECTIVES The study evaluated the efficacy and safety of a short-acting reduced-dose fibrinolytic regimen to promote early infarct-related artery (IRA) patency during the inherent delay experienced by infarct patients referred for angioplasty as the principal recanalization modality. BACKGROUND Previous approaches using long-acting, full-dose thrombolytic infusions rarely showed benefit, but they did increase adverse event rates. METHODS Following aspirin and heparin, 606 patients were randomized to a 50-mg bolus of recombinant tissue-type plasminogen activator (rt-PA) (alpha half-life 4.5 min) or to placebo followed by immediate angiography with angioplasty if needed. The end points included patency rates on catheterization laboratory (cath lab) arrival, technical results when PTCA (percutaneous transluminal coronary angioplasty) was performed, complication rates, and left ventricular (LV) function by treatment assignment and time to restored patency following angioplasty. RESULTS Patency on cath lab arrival was 61% with rt-PA (28% Thrombolysis in Myocardial Infarction trial [TIMI]-2, 33% TIMI-3), and 34% with placebo (19% TIMI-2, 15% TIMI-3) (p = 0.001). Rescue and primary PTCA restored TIMI-3 in closed arteries equally (77%, 79%). No differences were observed in stroke or major bleeding. Left ventricular function was similar in both treatment groups, but convalescent ejection fraction (EF) was highest with a patent IRA (TIMI-3) on cath lab arrival (62.4%) or when produced by angioplasty within an hour of bolus (62.5%). However, in 88% of angioplasties, the delay exceeded 1 h: convalescent EF 57.3%. CONCLUSIONS Tailored thrombolytic regimens compatible with subsequent interventions lead to more frequent early recanalization (before cath arrival), which facilitates greater LV function preservation with no augmentation of adverse events.

Randomized Comparison of Enoxaparin, a Low-Molecular-Weight Heparin, With Unfractionated Heparin Adjunctive to Recombinant Tissue Plasminogen Activator Thrombolysis and Aspirin Second Trial of Heparin and Aspirin Reperfusion Therapy (HART II)

Background—Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. Methods and Results—Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups. Conclusions—Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.

Extended Mortality Benefit of Early Postinfarction Reperfusion

Background —Reperfusion therapy for myocardial infarction, understood to reduce mortality by preserving left ventricular function, was initially expected to provide increasing benefits over time. Surprisingly, large controlled thrombolysis trials demonstrated maximum benefit at 4 to 6 weeks with no subsequent increased treatment advantage. Such studies, however, compared groups by assigned treatment, not physiological effectiveness. Methods and Results —We calculated 2-year survival differences among 2431 myocardial infarction patients according to early infarct artery patency and outcome left ventricular ejection fraction using Kaplan-Meier curves. Hazard ratios for significant survival determinants were derived from Cox regression models. Two-year vital status (minimum, 688 days) was determined in 2375 patients (97.7%). A substantial mortality advantage for early complete reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade 3) and for preserved ejection fraction occurred beyond 30 days. The unadjusted hazard ratio for the TIMI 3 group compared with lesser grades at 30 days was 0.57 (95% confidence interval [CI], 0.35 to 0.94) and 30 days to ≥688 days was 0.39 (95% CI, 0.22 to 0.69). Consequently, early TIMI 3 flow was associated with approximately a 3 patient per 100 mortality reduction the first month with an additional 5 lives per 100 from 30 days to 2 years. For ejection fraction >40% compared with ≤40%, the unadjusted hazard ratio was 0.25 (95% CI, 0.16 to 0.37) at 30 days and 0.22 (95% CI, 0.15 to 0.33) after 30 days through 2 years (lives saved, ≈9 and 11 per 100, respectively). Conclusions —Successful reperfusion and myocardial salvage produce significant mortality benefits that are amplified beyond the initial 30 days.

Prevalence and Effect on Health-Related Quality of Life of Overactive Bladder in Older Americans:: Results from the Epidemiology of Lower Urinary Tract Symptoms Study

OBJECTIVE: To evaluate the prevalence and effect of overactive bladder (OAB) on healthcare‐seeking behavior, mental health, and generic and condition‐specific health‐related quality of life (HRQL) in older adults.

Clinical predictors of early infarct-related artery patency following thrombolytic therapy : Importance of body weight, smoking history, infarct-related artery and choice of thrombolytic regimen : The GUSTO-I experience

OBJECTIVES The purpose of this study was to determine patient characteristics that are a priori predictors of early infarct related artery patency following thrombolytic therapy, and to provide a paradigm which may identify patients who would be most likely to achieve restoration of normal (TIMI 3) coronary flow in response to thrombolytic therapy. BACKGROUND Restoration of infarct-related artery perfusion in acute myocardial infarction is necessary for preservation of ventricular function and mortality reduction. Clinical variables that are a priori predictors of early patency with currently available thrombolytic regimens have not been fully characterized. METHODS The probability of early infarct-related artery patency (TIMI 3 flow) was determined by multivariable logistic regression. We determined a reduced (parsimonious) model for predicting early (90 min) infarct-related artery patency (TIMI grade 3) based on data from 1,030 patients in the GUSTO-I Angiographic study. RESULTS Predictors of 90 min TIMI 3 flow are use of an accelerated t-PA regimen (vs. streptokinase containing regimens) (chi2=39.1; p < or = 0.0001), infarct related artery (RCA/Lcx vs. LAD) (chi2=12.7; p=0.0004), body weight (chi2=10.3; p=0.001) and history of smoking (chi2=7.4; p=0.007). Time from symptom onset to treatment was not significant (p=0.71). CONCLUSIONS The efficacy of currently available thrombolytic regimens is chiefly dependent on choice of thrombolytic regimen, body weight, infarct-related coronary artery and smoking history. Clinical variables alone correctly predict a priori TIMI 3 flow in the infarct-related artery 64% of the time. Patients with body weights greater than 85 kg are at a significant disadvantage with regard to achieving successful thrombolysis compared to those with lesser body weights.

Outcomes from leiomyoma therapies: comparison with normal controls.

OBJECTIVE: To assess the severity of symptoms caused by uterine leiomyomas, their effect on health-related quality of life, and the change after treatment compared with a normal control group. METHODS: A multicenter nonrandomized prospective study was completed assessing 12-month outcomes from three leiomyoma treatments. Outcome measures included the Uterine Fibroid Symptom and Quality of Life and the Short Form 36 questionnaires. Women scheduled for hysterectomy, myomectomy, or uterine artery embolization were recruited, as well as normal control group members. Questionnaires were completed at baseline and at 6 and 12 months posttreatment. Baseline characteristics were summarized using descriptive statistics. General linear models were used to examine differences among the patient groups. RESULTS: A total of 375 patients completed baseline enrollment: 101 normal, 107 embolization, 61 myomectomy, and 106 hysterectomy. At baseline, the mean Uterine Fibroid Symptom and Quality of Life Symptom Severity score for women in the normal control group was 15.3 (±14.5) and 64.8 (±20) for the leiomyoma patients (P<.001). At 6 and 12 months, the mean Symptom score for women in the normal control group was unchanged, while the leiomyoma treatment group score reduced to a mean of 17.8 (±17.5) at 12 months. Similar magnitude changes occurred among the Uterine Fibroid Symptom and Quality of Life health-related quality of life subscale scores for the normal control group members and leiomyoma patients. At 12 months, the hysterectomy group reported significantly lower symptoms and better health-related quality of life than the other two therapies (P<.001). CONCLUSION: At 12 months after treatment, all three leiomyoma therapies resulted in substantial symptom relief, to near normal levels, with the greatest improvement after hysterectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00390494. LEVEL OF EVIDENCE: II

The responsiveness of the uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL)

BackgroundA number of noninvasive alternatives to hysterectomy have become available as treatments for uterine fibroids. These alternative therapies, however, may not relieve all symptoms. Consequently, the need for patient-reported outcomes to assess symptom reduction of uterine fibroids has become increasingly important to evaluate the clinical success of patients who choose these alternative therapies. The purpose of the study was to examine the responsiveness of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) with treatment of uterine fibroids.MethodsThe responsiveness of the UFS-QOL was assessed as a post-hoc analysis of patients treated with MRI-guided focused ultrasound thermal ablation (MRgFUS) for uterine fibroids. The UFS-QOL and SF-36 were completed at baseline and months 1, 3, and 6. Patient perceived overall treatment effect (OTE) was assessed at month 3, while satisfaction with treatment was collected at month 6. The responsiveness of the UFS-QOL was examined using effect sizes and change scores by patient-reported overall treatment effect and satisfaction.ResultsA total of 102 women with complete UFS-QOL data were included in the analysis; the mean age was 45 years and 79% were Caucasian. From baseline to 6 months, significant improvements were observed in UFS-QOL Symptom Severity and all Health-Related Quality of Life (HRQL) subscale scores (p < 0.0001). When examining change in general health status over the 6-month follow-up period, significant improvements were noted in all 8 SF-36 subscales. The UFS-QOL was highly responsive with subscale effect sizes ranging from 0.74 for Sexual Function to -1.9 for Symptom Severity. Improvements in UFS-QOL subscales were associated with patient perceptions of perceived benefit and treatment satisfaction.ConclusionThe UFS-QOL is responsive to treatment for uterine fibroids and is a useful outcome measure for uterine-sparing uterine fibroid treatments.

Opioid-induced constipation in patients with chronic noncancer pain in the Usa, Canada, germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review

Background The characteristics of patients who suffer from noncancer pain and opioid-induced constipation are not well understood. Methods Cross-sectional patient survey and chart review data from the baseline assessment of an ongoing longitudinal study in the USA, Canada, Germany, and the UK were evaluated via descriptive statistics. Participants had confirmation of daily opioid therapy ≥30 mg for ≥4 weeks and self-reported opioid-induced constipation. Response to laxatives was defined by classifying participants into categories of laxative use and evaluating the prevalence of inadequate response to one laxative agent and two or more agents from at least two different laxative classes. Outcomes included the Patient Assessment of Constipation-Symptoms, Work Productivity and Activity Impairment Questionnaire-Specific Health Problem, EuroQOL 5 Dimensions, and Global Assessment of Treatment Benefit, Satisfaction, and Willingness to Continue. Results Patients reported a mean of 1.4 bowel movements not preceded by laxatives and 3.7 bowel movements with laxative use per week; 83% wanted at least one bowel movement per day. Most commonly reported on Patient Assessment of Constipation-Symptoms were straining/squeezing to pass bowel movements (83%), bowel movements too hard (75%), flatulence (69%), and bloating (69%). Eighty-four percent were taking natural or behavioral therapies; 60% were taking at least one over-the-counter laxative; and 19% were taking at least one prescription laxative. Prevalence of inadequate response to one laxative agent was 94%; inadequate response to two or more agents from at least two different laxative classes was 27%. Mean Work Productivity and Activity Impairment Questionnaire-Specific Health Problem values for percent work time missed, percent impairment while working, and percent activity impairment were 9%, 32% (equivalent of 14 hours of lost productivity per week), and 38%. Mean EuroQOL 5 Dimensions index and visual analog scale scores were 0.49 and 50.6, respectively. Forty-four percent reported being satisfied with their treatment for constipation. Conclusion Patients treated with opioids for noncancer pain commonly endure constipation symptoms that limit their work productivity and overall health-related quality of life while adhering to treatments that provide little relief. Further research is needed to identify more efficacious constipation therapies for this patient population.

The Impact of OAB on Sexual Health in Men and Women: Results from EpiLUTS

INTRODUCTION Prior research suggests that overactive bladder (OAB) is common and adversely affects sexuality in both men and women. However, more data are needed from population-based studies to evaluate the impact OAB on sexual health. AIM To describe sexual health outcomes in men and women with continent and incontinent OAB (C-OAB, I-OAB) compared to those with no/minimal urinary symptoms (NMS) and to evaluate correlates of decreased sexual activity and enjoyment in men and women, and correlates of erectile dysfunction (ED), ejaculatory dysfunction (EjD), and premature ejaculation (PE) in men. METHODS A cross-sectional, population-representative survey was conducted via the Internet in the United Kingdom, Sweden, and United States. OAB was assessed via a questionnaire based on current International Continence Society definitions. Descriptive statistics were used to compare outcomes for those with I-OAB, C-OAB and NMS, and logistic regressions were used to evaluate predictors of sexual functioning. MAIN OUTCOME MEASURES Participants responding to the sexual health portion of the survey were asked questions about sexual activity and satisfaction. Other outcomes included two domains from the Abbreviated Sexual Function Questionnaire, the erectile function domain of the International Index of Erectile Function, and questions assessing EjD and PE. RESULTS Survey response was 59.2%; 6,326 men and 8,085 women participated in the sexual health portion of the survey. Across outcomes, I-OAB and C-OAB were associated with worse sexual health as compared to those with NMS. Logistic regressions showed that those with I-OAB and C-OAB were significantly (P<0.0001) more likely to report diminished sexual activity and enjoyment of sex. I-OAB and C-OAB were also significant predictors of ED and EjD in men, but not PE. CONCLUSIONS The impact of OAB is evident across domains of sexual health in both men and women. Sexual health should be assessed in men and women presenting with OAB.

Evolution of Early TIMI 2 Flow After Thrombolysis for Acute Myocardial Infarction

BACKGROUND Patients with early Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolysis appear to have outcomes similar to thrombolytic failures. To evaluate the origin and evolution of early TIMI 2 flow, we examined early and late angiographic and ventriculographic data from the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-1) angiographic study. METHODS AND RESULTS Of the 914 patients with both 90-minute and 5- to 7-day catheterizations, 278 patients had TIMI grade 2 flow at 90 minutes. At follow-up, 188 (67%) had improved to TIMI grade 3 flow. At 90 minutes, patients with TIMI grade 2 flow had greater infarct vessel narrowing and a significantly greater incidence of thrombus than patients with TIMI grade 3 flow. At the 5- to 7-day follow-up, patients whose flow had improved from TIMI grade 2 at 90 minutes to grade 3 flow at follow-up had larger-caliber vessels (minimum luminal diameter, 0.99 +/- 0.47 versus 0.84 +/- 0.48 mm; P = .03) and a lower incidence of visible thrombus (26% versus 38%, P = .04) than those with persistent TIMI grade 2 flow. These patients also had a higher mean ejection fraction (57.5 +/- 14.1% versus 52.8 +/- 12.9%, P = .02) and better infarct zone wall motion (-2.1 +/- 1.5 versus -2.6 +/- 1.3 SD per chord, P = .01) at the 5- to 7-day follow-up. Patients in whom flow improved from TIMI grade 2 at 90 minutes to TIMI grade 3 by 5 to 7 days had significantly better left ventricular function than patients with persistent TIMI grade 0, 1, or 2 flow and constituted a group whose left ventricular function was intermediate between those who had no reperfusion (TIMI grades 0 and 1) and those whose reperfusion was complete (TIMI grade 3). CONCLUSIONS These data suggest that incomplete clot lysis plays a significant role in the pathogenesis of TIMI grade 2 flow. Furthermore, early TIMI grade 2 flow may be sufficient to provide prolonged myocyte viability, which will further recover if flow normalizes.