A Pilot Study to Assess the Feasibility of Collecting and Transmitting Clinical Trial Data with Mobile Technologies.

BACKGROUND: The use of mobile technologies for data capture and transmission has the potential to streamline clinical trials, but researchers lack methods for collecting, processing, and interpreting data from these tools. OBJECTIVES: To assess the performance of a technical platform for collecting and transmitting data from six mobile technologies in the clinic and at home, to apply methods for comparing them to clinical standard devices, and to measure their usability, including how willing subjects were to use them on a regular basis. METHODS: In part 1 of the study, conducted over 3 weeks in the clinic, we tested two device pairs (mobile vs. clinical standard blood pressure monitor and mobile vs. clinical standard spirometer) on 25 healthy volunteers. In part 2 of the study, conducted over 3 days both in the clinic and at home, we tested the same two device pairs as in part 1, plus four additional pairs (mobile vs. clinical standard pulse oximeter, glucose meter, weight scale, and activity monitor), on 22 healthy volunteers. RESULTS: Data collection reliability was 98.1% in part 1 of the study and 95.8% in part 2 (the percentages exclude the wearable activity monitor, which collects data continuously). In part 1, 20 of 1,049 overall expected measurements were missing (1.9%), and in part 2, 45 of 1,083 were missing (4.2%). The most common reason for missing data was a single malfunctioning spirometer (13 of 20 total missed readings) in part 1, and that the subject did not take the measurement (22 of 45 total missed readings) in part 2. Also in part 2, a higher proportion of at-home measurements than in-clinic readings were missing (12.6 vs. 2.7%). The data from this experimental study were unable to establish repeatability or agreement for every mobile technology; only the pulse oximeter demonstrated repeatability, and only the weight scale demonstrated agreement with the clinical standard device. Most mobile technologies received high "willingness to use" ratings from the patients on the questionnaires. CONCLUSIONS: This study demonstrated that the wireless data transmission and processing platform was dependable. It also identified three critical areas of study for advancing the use of mobile technologies in clinical research: (1) if a mobile technology captures more than one type of endpoint (such as blood pressure and pulse), repeatability and agreement may need to be established for each endpoint to be included in a clinical trial; (2) researchers need to develop criteria for excluding invalid device readings (to be identified by algorithms in real time) for the population studied using ranges based on accumulated subject data and established norms; and (3) careful examination of a mobile technology's performance (reliability, repeatability, and agreement with accepted reference devices) during pilot testing is essential, even for medical devices approved by regulators.

Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial.

BACKGROUND: Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention. METHODS: All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up. RESULTS: Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio [HR] 0.43; 95% confidence interval [CI], 0.22-0.85; P = .02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P = .05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P = .27). CONCLUSIONS: PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.

Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.

BACKGROUND: The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. OBJECTIVES: The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. METHODS: Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. RESULTS: Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. CONCLUSIONS: Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921).

Clopidogrel with or without omeprazole in coronary artery disease.

BACKGROUND: Gastrointestinal complications are an important problem of antithrombotic therapy. Proton-pump inhibitors (PPIs) are believed to decrease the risk of such complications, though no randomized trial has proved this in patients receiving dual antiplatelet therapy. Recently, concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel. METHODS: We randomly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo, in addition to aspirin. The primary gastrointestinal end point was a composite of overt or occult bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or perforation. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, revascularization, or stroke. The trial was terminated prematurely when the sponsor lost financing. RESULTS: We planned to enroll about 5000 patients; a total of 3873 were randomly assigned and 3761 were included in analyses. In all, 51 patients had a gastrointestinal event; the event rate was 1.1% with omeprazole and 2.9% with placebo at 180 days (hazard ratio with omeprazole, 0.34, 95% confidence interval [CI], 0.18 to 0.63; P<0.001). The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo (hazard ratio, 0.13; 95% CI, 0.03 to 0.56; P = 0.001). A total of 109 patients had a cardiovascular event, with event rates of 4.9% with omeprazole and 5.7% with placebo (hazard ratio with omeprazole, 0.99; 95% CI, 0.68 to 1.44; P = 0.96); high-risk subgroups did not show significant heterogeneity. The two groups did not differ significantly in the rate of serious adverse events, though the risk of diarrhea was increased with omeprazole. CONCLUSIONS: Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI. (Funded by Cogentus Pharmaceuticals; ClinicalTrials.gov number, NCT00557921.).

AngioJet Rheolytic thrombectomy during rescue PCI for failed thrombolysis: a single-center experience.

BACKGROUND: Previous studies have shown the efficacy of AngioJet Rheolytic Thrombectomy (RT) in reducing thrombus burden and improving coronary flow in acute myocardial infarction (MI). No study has specifically evaluated the use of AngioJet RT in patients undergoing rescue percutaneous coronary intervention (PCI) for failed thrombolysis, a setting that may be particularly beneficial given the extensive thrombus burden. The objective of this study was to evaluate the efficacy and safety of AngioJet RT during rescue PCI for failed thrombolysis. METHODS: 214 consecutive patients were transferred to Good Samaritan Hospital to undergo rescue PCI for failed thrombolysis from January 2000 to October 2004. From this cohort, 32 patients (age 57 +/- 9, 30% male) undergoing AngioJet RT for rescue PCI (RT group) were identified and matched by initial thrombolysis in MI (TIMI) flow and infarct related artery (IRA) location to 32 patients (age 60 +/- 12, 24% male) undergoing rescue PCI without AngioJet RT (Control group). TIMI frame count and TIMI thrombus grade were assessed at initial and final angiography. Angiographic success (TIMI 3 flow, < 50% residual stenosis) and in-hospital clinical events, including bleeding complications and major adverse cardiac events (MACE) such as death, recurrent MI, target vessel revascularization and emergent bypass surgery were evaluated. Clinical success was defined as angiographic success in the absence of MACE. RESULTS: Baseline clinical characteristics were similar in both groups, except patients undergoing AngioJet RT were more likely to be males and less likely to be intubated on transfer. 30/32 (94%) patients achieved a TIMI thrombus grade of 0 in the RT group, compared to 22/32 (69%) in the Control group. Final IRA TIMI frame count was similar in the RT compared to the Control group (33 +/- 21 vs. 38 +/- 23, p NS, respectively). The occurrence of no reflow was significantly lower in the RT compared to the Control group (13% vs. 56%, p < 0.001, respectively). There was a trend for higher angiographic success in the RT compared to the control group (93% vs. 78%, p = 0.07, respectively). Clinical success was higher in the RT compared to the Control group (91% vs. 71%, p = 0.05, respectively). There were no differences in bleeding complications or MACE between the groups. CONCLUSION: AngioJet RT in high-risk patients undergoing rescue PCI for failed thrombolysis is safe and more effective in decreasing thrombus burden and preventing no reflow than conventional PCI.

Rescue percutaneous coronary intervention for failed thrombolysis.

BACKGROUND: Previous studies of rescue percutaneous coronary intervention (PCI) for failed thrombolysis yielded conflicting results. In the current era of newer thrombolytic agents, coronary stents, glycoprotein IIb/IIIa inhibitors, and aggressive hemodynamic support, the outcome of this high-risk patient group has not been characterized. METHODS: From January 2000 to October 2004, 214 consecutive patients were transferred and underwent emergent coronary angiography following failed thrombolysis. One hundred and fifty five (72%) underwent immediate PCI, 23 (11%) underwent delayed PCI, and 36 (17%) received surgical revascularization or medical therapy. Medical records and angiograms for the entire PCI cohort (n=178) were reviewed for in-hospital events including bleeding complications, stroke, recurrent ischemia or myocardial infarction (MI), target vessel revascularization (TVR), and death. RESULTS: Time from symptom onset to thrombolysis (mean +/- standard deviation) was 5.6 +/- 11.9 hr, and time from thrombolysis to angiography was 7.0 +/- 5.5 hr. The study cohort was critically ill, with 9.6% experiencing cardiac arrest, 21% in cardiogenic shock, and 12% intubated prior to transfer. Coronary stents were placed in 88%, Rheolytic thrombectomy was used in 21%, an intraaortic balloon pump was placed in 17%, and a glycoprotein IIb/IIIa inhibitor was administered in 92%. Patients receiving delayed PCI had higher TIMI 3 flow grade at initial angiography than those receiving immediate PCI (83% vs. 34%, respectively, P < 0.0001). Angiographic success was 90% for the entire PCI cohort, 89% for the immediate PCI group, and 100% for the delayed PCI group. Clinical success (angiographic success and freedom from major adverse cardiac events) was 85% for the entire PCI cohort, 83% for the immediate PCI group, and 100% for the delayed PCI group. Severe and moderate bleeding complications occurred in 7.3%, stroke in 1.7%, recurrent ischemia or MI in 7.3%, and TVR in 3.4%. Overall, in-hospital mortality for the entire PCI cohort was 3.4%. CONCLUSIONS: This observational, consecutive, real-world study of contemporary rescue PCI for failed thrombolysis shows a high use of coronary stents, Rheolytic thrombectomy, glycoprotein IIb/IIIa inhibitors, and intraaortic balloon pump placement. Angiographic and clinical success was high with low bleeding complications and low in-hospital mortality, suggesting that prospective, randomized trials using contemporary interventional therapy for rescue PCI be considered.

Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women.

BACKGROUND: In postmenopausal women with coronary artery disease, conjugated equine estrogen with or without continuous administration of medroxyprogesterone acetate has failed to slow the progression of atherosclerosis. Whether 17beta-estradiol (the endogenous estrogen molecule) alone or administered sequentially with medroxyprogesterone acetate can slow the progression of atherosclerosis is unknown. METHODS: We conducted a double-blind, placebo-controlled trial in 226 postmenopausal women (mean age, 63.5 years) who had at least one coronary-artery lesion. Participants were randomly assigned to usual care (control group), estrogen therapy with micronized 17beta-estradiol alone (estrogen group), or 17beta-estradiol plus sequentially administered medroxyprogesterone acetate (estrogen-progestin group). In all patients the low-density lipoprotein (LDL) cholesterol level was reduced to a target of less than 130 mg per deciliter. The primary outcome was the average per-participant change between base-line and follow-up coronary angiograms in the percent stenosis measured by quantitative coronary angiography. RESULTS: After a median of 3.3 years of follow-up, the mean (+/-SE) change in the percent stenosis in the 169 participants who had a pair of matched angiograms was 1.89+/-0.78 percentage points in the control group, 2.18+/-0.76 in the estrogen group, and 1.24+/-0.80 in the estrogen-progestin group (P=0.66 for the comparison among the three groups). The mean difference in the percent stenosis between the estrogen group and the control group was 0.29 percentage point (95 percent confidence interval, -1.88 to 2.46), and the mean difference between the estrogen-progestin group and the control group was -0.65 (95 percent confidence interval, -2.87 to 1.57). CONCLUSIONS: In older postmenopausal women with established coronary-artery atherosclerosis, 17beta-estradiol either alone or with sequentially administered medroxyprogesterone acetate had no significant effect on the progression of atherosclerosis.

Erectile dysfunction in the cardiac patient: how common and should we treat?

PURPOSE: Risk factors for erectile dysfunction (ED) (hypertension, diabetes, smoking, lipid abnormality) are also risk factors for coronary artery disease. However, most cardiologists do not routinely ask about ED and patients often are reluctant or embarrassed to discuss it. We determined how common ED was in a group of patients with chronic stable coronary artery disease. MATERIALS AND METHODS: We administered the validated Sexual Health Inventory for Men (SHIM) 5-item questionnaire, based on the International Index of Erectile Function questionnaire, to 76 men with chronic stable coronary artery disease during routine outpatient cardiology visits. Most of these men had not previously discussed ED with their cardiologist. RESULTS: The mean patient age was 64 years (range 40 to 82). The questionnaire took about 5 minutes to complete. Of the patients 47% were on beta blockers, 92% statins, 28% diuretics. SHIM score was 21 or less in 53 men (70%), which is indicative of ED. Of the patients 75% had some difficulty achieving erections (question 2) and 67% had some difficulty maintaining an erection after penetration (question 3). The questionnaire reflected successful sildenafil treatment in 4 patients (SHIM scores 23 to 25). If these 4 men are included as having had ED then 57 of 76 (75%) had ED or recent history of ED. CONCLUSIONS: ED is extremely common in men with chronic coronary artery disease (affecting approximately 75%) yet most cardiologists do not ask about it. The SHIM is a useful, quick and inexpensive tool for discussion and diagnosis of ED in this population. Although it is well established that cardiovascular risk factors are associated with erectile dysfunction, once it is present there is mixed information on whether treating the risk factors will treat the ED. Problems appear to be that lifestyle modification in midlife may simply be too late to effect a change, and some antihypertensive and lipid lowering drugs may actually exacerbate ED. Oral therapy for ED, namely the PDE5 inhibitors, is effective and safe in most cardiac and hypertensive patients. Organic nitrates such as nitroglycerin remain a contraindication to the concomitant use of these drugs. Guidelines for treatment of ED in the cardiac patient issued by the American College of Cardiology/American Heart Association and Princeton Guidelines may be useful in the approach to the cardiac patient with ED.