Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients.

Medical practitioners have treated atherosclerotic disease with chelation therapy for over 50 years. Lack of strong of evidence led conventional practitioners to abandon its use in the 1960s and 1970s. This relegated chelation therapy to complementary and alternative medicine practitioners, who reported good anecdotal results. Concurrently, the epidemiologic evidence linking xenobiotic metals with cardiovascular disease and mortality gradually accumulated, suggesting a plausible role for chelation therapy. On the basis of the continued use of chelation therapy without an evidence base, the National Institutes of Health released a Request for Applications for a definitive trial of chelation therapy. The Trial to Assess Chelation Therapy (TACT) was formulated as a 2 × 2 factorial randomized controlled trial of intravenous EDTA-based chelation vs. placebo and high-dose oral multivitamins and multiminerals vs. oral placebo. The composite primary endpoint was death, reinfarction, stroke, coronary revascularization, or hospitalization for angina. A total of 1708 post-MI patients who were 50 years or older with a creatinine of 2.0 or less were enrolled and received 55,222 infusions of disodium EDTA or placebo with a median follow-up of 55 months. Patients were on evidence-based post-MI medications including statins. EDTA proved to be safe. EDTA chelation therapy reduced cardiovascular events by 18%, with a 5-year number needed to treat (NNT) of 18. Prespecified subgroup analysis revealed a robust benefit in patients with diabetes mellitus with a 41% reduction in the primary endpoint (5-year NNT = 6.5), and a 43% 5-year relative risk reduction in all-cause mortality (5-year NNT = 12). The magnitude of benefit is such that it suggests urgency in replication and implementation, which could, due to the excellent safety record, occur simultaneously.

Incidence of postoperative acute kidney injury in patients with chronic kidney disease undergoing minimally invasive valve surgery.

BACKGROUND: We hypothesize that minimally invasive valve surgery in patients with chronic kidney disease (CKD) is superior to a conventional median sternotomy. METHODS: We retrospectively analyzed 1945 consecutive patients who underwent isolated valve surgery. Included were patients with CKD stages 2 to 5. In-hospital mortality, composite complication rates, and intensive care unit and total hospital lengths of stay of those who underwent a minimally invasive approach were compared with those who underwent a standard median sternotomy. Resource use was approximated based on intensive care unit and total hospital lengths of stay. RESULTS: There were 688 patients identified; 510 (74%) underwent minimally invasive surgery, and 178 (26%) underwent a median sternotomy. There was no significant difference in mortality. Minimally invasive surgery was associated with fewer composite complications (33.1% vs 49.4%; odds ratio, 0.5; P ≤ .001), shorter intensive care unit (48 [interquartile range {IQR}, 33-74] hours vs 71 [IQR, 42-96] hours; P < .01), and hospital (8 [IQR, 6-9] days vs 10 [IQR, 8-15] days; P < .001) lengths of stay, and a lower incidence of acute kidney injury (8% vs 14.7%; odds ratio, 0.5; P = .01), compared with median sternotomy. In a multivariable analysis, minimally invasive surgery was associated with a 60% reduction in the risk of development of postoperative acute kidney injury. CONCLUSIONS: In patients with CKD undergoing isolated valve surgery, minimally invasive valve surgery is associated with reduced postoperative complications and lower resource use.

Incidence of postoperative atrial fibrillation in patients undergoing minimally invasive versus median sternotomy valve surgery.

BACKGROUND: Atrial fibrillation (AF) after cardiac surgery is associated with increased morbidity and hospital length of stay. Our objective was to determine whether a minimally invasive approach to isolated valve surgery reduced the incidence of postoperative AF. METHODS: Patients without a history of arrhythmia, who underwent isolated aortic or mitral valve surgery between January 2005 and August 2011, were included. The incidence of postoperative AF in those who underwent a minimally invasive approach was compared with that of patients undergoing median sternotomy surgery. Resource utilization was approximated on the basis of intensive care unit and total hospital lengths of stay. RESULTS: A total of 571 patients were identified (413 minimally invasive and 158 median sternotomy). No significant differences in baseline characteristics existed between groups. The incidence of postoperative AF (25% vs 37%; P = .002), use of intraoperative blood products (52% vs 83%; P < .001), and prolonged intubation (≥24 hours) (12% vs 20%; P = .008) were significantly less in the minimally invasive group. The intensive care unit and hospital lengths of stay were 45 hours (interquartile range [IQR], 28-66 hours) versus 53 hours (IQR, 45-91 hours) (P < .001), and 5 days (IQR, 4-7 days) versus 8 days (IQR, 6-11 days) (P < .001) for the minimally invasive and median sternotomy groups, respectively. Multivariable analysis revealed a decreased risk of postoperative AF in patients undergoing minimally invasive surgery (odds ratio, 0.4; 95% confidence intervals, 0.24-0.66; P < .001). CONCLUSIONS: A minimally invasive approach for isolated valve surgery reduces postoperative AF and resource use when compared with median sternotomy.

Cost of medical services in older patients with heart failure: those receiving enhanced monitoring using a computer-based telephonic monitoring system compared with those in usual care: the Heart Failure Home Care trial.

BACKGROUND: Prior studies suggest that disease management programs may be effective in improving clinical and economic outcomes in patients with heart failure. Whether these types of programs can lower health care cost and be adapted to the primary care setting is unknown. This study was designed to assess the impact of a home-based disease management program, the Alere DayLink HF Monitoring System (HFMS), on the clinical and economic outcomes of Medicare beneficiaries recently hospitalized for heart failure who received the care from a community-based primary care practitioner. METHODS AND RESULTS: The Heart Failure Home Care trial was a multicenter, randomized, controlled trial of sophisticated, monitoring of heart failure patients with an interactive program versus standard heart failure care with enhanced patient education and follow-up (SC) in Medicare-eligible patients. The study endpoints included cardiovascular death or rehospitalization for heart failure, length of hospital stay, total patient cost, and cost to Medicare at 6 months of enrollment. A total of 315 patients age ≥ 65 years old were randomized: 160 to the HFMS and 155 to SC. There were no significant statistical differences between the groups in regards to 6-month cardiac mortality, rehospitalizations for heart failure, or length of hospital stay. Of those, 304 patients had their Medicare data available. The information from the Medicare claims data was used to determine the cost. Information from the trial was used to determine costs of out-patient drugs and the interventions. The 6-month mean Medicare costs were estimated to be $17,837 and $13,886 for the HFMS and the SC groups, respectively. We found that overall medical costs of medicare patients were significantly higher for patients who were randomized to the HFMS arm than they were for the patients randomized to the SC arm. CONCLUSIONS: Our study results suggest that enhanced patient education and follow-up is as successful as a sophisticated home monitoring device with an interactive program and less costly in patients who are elderly and receive the care from a community-based primary care practitioner.

Quality of life after late invasive therapy for occluded arteries.

BACKGROUND: The open-artery hypothesis postulates that late opening of an infarct-related artery after myocardial infarction will improve clinical outcomes. We evaluated the quality-of-life and economic outcomes associated with the use of this strategy. METHODS: We compared percutaneous coronary intervention (PCI) plus stenting with medical therapy alone in high-risk patients in stable condition who had a totally occluded infarct-related artery 3 to 28 days after myocardial infarction. In 951 patients (44% of those eligible), we assessed quality of life by means of a battery of tests that included two principal outcome measures, the Duke Activity Status Index (DASI) (which measures cardiac physical function on a scale from 0 to 58, with higher scores indicating better function) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being). Structured quality-of-life interviews were performed at baseline and at 4, 12, and 24 months. Costs of treatment were assessed for 458 of 469 patients in the United States (98%), and 2-year cost-effectiveness was estimated. RESULTS: At 4 months, the medical-therapy group, as compared with the PCI group, had a clinically marginal decrease of 3.4 points in the DASI score (P=0.007). At 1 and 2 years, the differences were smaller. No significant differences in psychological well-being were observed. For the 469 patients in the United States, cumulative 2-year costs were approximately $7,000 higher in the PCI group (P<0.001), and the quality-adjusted survival was marginally longer in the medical-therapy group. CONCLUSIONS: PCI was associated with a marginal advantage in cardiac physical function at 4 months but not thereafter. At 2 years, medical therapy remained significantly less expensive than routine PCI and was associated with marginally longer quality-adjusted survival. (ClinicalTrials.gov number, NCT00004562.)

Direct treatment cost of atrial fibrillation in the elderly American population: a Medicare perspective.

OBJECTIVE: Although atrial fibrillation (AF) is the most commonly sustained arrhythmia in adults, few studies have examined the direct treatment cost of AF. METHODS: A Medicare database of a 5% random national sample of all beneficiaries was used to identify patients diagnosed with AF in 2003 and to follow them for 1 year after diagnosis. These patients were matched on a 1:1 basis by age, gender and race. The incremental cost of treating AF was calculated with multivariate regression models adjusting for covariates. RESULTS: In total, 55,260 subjects developed new AF, of which 69% were >or=75 years old, 54% were female and 91% were White. The adjusted mean incremental treatment cost of AF was $14,199 (95% confidence interval $13,201-15,001; p<0.01). Some of this cost was attributable to the incidence of stroke and heart failure at the 1-year post-AF diagnosis. A significantly higher proportion of AF patients experienced stroke (23.1 vs. 13.3%; p<0.01) and heart failure (36.7 vs. 10.4%; p<0.01) compared with Medicare beneficiaries without AF. CONCLUSIONS: Mean incremental direct treatment costs for Medicare beneficiaries with AF were higher than previously reported. Interventions that can reduce the incidence of AF and its complications may also reduce the national economic impact of AF.

Cost-effectiveness of dual-chamber pacing compared with ventricular pacing for sinus node dysfunction.

BACKGROUND: Compared with single-chamber ventricular pacing, dual-chamber pacing can reduce adverse events and, as a result, improve quality of life in patients paced for sick sinus syndrome. It is not clear, however, how these benefits compare with the increased cost of dual-chamber pacemakers. METHODS AND RESULTS: We used 4-year data from a 2010-patient, randomized trial to estimate the incremental cost-effectiveness of dual-chamber pacing compared with ventricular pacing and then projected these findings over the patients' lifetimes by using a Markov model that was calibrated to the first 5 years of in-trial data. To assess the stability of the findings, we performed 1000 bootstrap analyses and multiple sensitivity analyses. During the first 4 years of the trial, dual-chamber pacemakers increased quality-adjusted life expectancy by 0.013 year per subject at an incremental cost-effectiveness ratio of 53,000 dollars per quality-adjusted year of life gained. Over a lifetime, dual-chamber pacing was projected to increase quality-adjusted life expectancy by 0.14 year with an incremental cost-effectiveness ratio of approximately 6800 dollars per quality-adjusted year of life gained. In bootstrap analyses, dual-chamber pacing was cost-effective in 91.9% of simulations at a threshold of 50,000 dollars per quality-adjusted year of life and in 93.2% of simulations at a threshold of 100,000 dollars. Its cost-effectiveness ratio was also below this threshold in numerous sensitivity analyses that varied key estimates. CONCLUSIONS: For patients with sick sinus syndrome requiring pacing, dual-chamber pacing increases quality-adjusted life expectancy at a cost that is generally considered acceptable.

Health values before and after pacemaker implantation.

BACKGROUND: Health value or utility is the abstracted magnitude of a person's preference for quality and quantity of life. It reflects how much lifetime with the patient's current health condition a patient is willing to exchange for a life in excellent health. Health values are used in cost-effectiveness analysis as a means of calculating quality-adjusted years of life. OBJECTIVE: This study assessed the health values of elderly patients before and after pacemaker implantation. METHODS: We prospectively examined 398 patients from the Pacemaker Selection in the Elderly study, in which patients were randomized to either VVIR or DDDR mode. Health values were estimated with the time tradeoff method before implantation and at 3, 9, and 18 months after implantation. RESULTS: The mean age of patients was 76 +/- 6 years; 234 patients (59%) were male. At baseline, patients were, on average, willing to exchange 5 years of current health for approximately 4 years in perfect health (value 0.76 +/- 0.06). There was no difference in baseline health values with implant diagnosis (sinus node dysfunction n = 172, 0.72, atrioventricular block n = 227, 0.75, other diagnoses n = 39, 0.78, P = not significant). The overall improvement in health values at 3 months after pacemaker implantation was 0.165 +/- 0.4 (P =.0001). The improvement in health values was independent of pacing mode (P =.6). The time tradeoff score was modestly correlated with other measurements of health-related quality of life. The change in time tradeoff score with time was not influenced by demographic characteristics such as age and sex, diagnoses, pacing mode, employment status, or history of angina. Patients with a lower functional class at enrollment (III or IV on the Specific Activity Scale) demonstrated an absolute improvement of 23% in their health values, whereas patients in class I or II improved only by 12%, (P =.03). CONCLUSIONS: Permanent pacemaker implantation for standard indications improves health values and descriptive health status measures. The values reported here may be used as a means of calculating the cost-effectiveness of different pacing modalities.

Outcome and cost-effectiveness of cardiopulmonary resuscitation after in-hospital cardiac arrest in octogenarians.

CONTEXT: Octogenarians are the fastest growing segment of the population and little is known about the results of cardiopulmonary resuscitation (CPR) after in-hospital cardiac arrest in this population. OBJECTIVE: We sought to investigate the clinical benefit and cost-effectiveness of CPR after in-hospital cardiac arrest in octogenarians. MAIN OUTCOME MEASURE: Years of life saved. DESIGN: Effectiveness data were obtained from a review of 91,372 hospital discharges from January 1st, 1993 until June 30th, 1996. Cardiac arrest was reported in 956 patients. The study group consisted of 474 patients > or = 80 years old. CPR costs included equipment and training, physician and nursing time and medications. Post-CPR expenses included in-hospital true cost, repeat hospitalizations, physician office visits, nursing home, rehabilitation, and chronic care hospital costs. Life expectancy of the patients who were still alive at the end of the study was estimated from census data. A utility of 0.8 was used to calculate quality-adjusted-life years saved (QALYS). We used a societal perspective for analysis. RESULTS: The study population was 86 +/- 4.8 years old (range 80-103), and 42% were male. Fifty-four patients (11%) were discharged alive, 35 to a chronic care facility and 19 to their home. Assuming that a cardiac arrest without CPR has 100% mortality, 12 octogenarians required treatment with CPR in order to save one life to hospital discharge. Similarly, 29 octogenarian patients with cardiac arrest have to be treated with CPR to net one long-term survivor (mean survival 21 months, with a range from 9 to 48 months). The cost-effectiveness ratio, after estimating the life expectancy of octogenarian survivors, was USD 50,412 per year of life saved, and USD 63,015 per QALYS. However, a utility of 0.5 yielded a cost of USD 100,825 per QALYS. CONCLUSION: In comparison with other life-saving strategies, CPR in octogenarians is effective. The favorable cost-effectiveness ratio is highly dependent on the patients' preference for quality rather than quantity of life, as expressed by the utility assumptions.