Long-term use of proton pump inhibitors, dose-response relationship and associated risk of ischemic stroke and myocardial infarction.

BACKGROUND: Use of proton pump inhibitors (PPIs) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI use, duration and dose, with risk of first-time ischemic stroke and myocardial infarction (MI) are poorly understood. METHODS: All Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose and used multiple cause-specific Cox regression and g-formula methods to analyze long-term use. RESULTS: Amongst 214 998 individuals, during a median follow-up of 5.8 years, there were 7916 ischemic strokes and 5608 MIs. Current PPI exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence interval (CI) 1.08-1.19) and MI (HR 1.31, CI 1.23-1.39) after adjusting for age, sex, comorbidities and concomitant medication. High-dose PPI was associated with increased rates of ischemic stroke (HR 1.31, CI 1.21-1.42) and MI (HR 1.43, CI 1.30-1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke (HR 1.02, CI 0.84-1.24) or MI (HR 1.15, CI 0.92-1.43). Long-term users of PPIs, compared with nonusers, had a 29% (CI 5%-59%) greater absolute risk of ischemic stroke and a 36% (CI 7%-73%) greater risk of MI within a 6-month period. CONCLUSION: Use of PPIs was associated with increased risks of first-time ischemic stroke and MI, particularly amongst long-term users and at high doses.

Coronary artery bypass graft type and outcomes in maintenance dialysis.

AIM: Patients with end-stage renal disease (ESRD) on maintenance dialysis have a high burden of coronary disease. Prior studies in non-dialysis patients show better outcomes in coronary artery bypass surgery using the internal mammary artery (IMA) compared with the saphenous vein graft (SVG), but less is known about outcomes in ESRD. We sought to compare the effectiveness of multivessel bypass grafting using IMA versus SVG in patients on maintenance dialysis in the United States. METHODS: Cohort study using data from the United States Renal Data System to examine IMA versus SVG in patients on maintenance dialysis undergoing multivessel coronary revascularization. We used Cox proportional hazards regression with multivariable adjustment in the full cohort and in a propensity-score matched cohort. The primary outcome was death from any cause; the secondary outcome was a composite of non-fatal myocardial infarction or death. RESULTS: Overall survival rates were low in this patient population (5-year survival in the matched cohort 25.3%). Use of the IMA compared to SVG was associated with lower risk of death (adjusted hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.84-0.92) and lower risk of the composite outcome (adjusted HR 0.89; CI 0.85-0.93). Results did not materially change in analyses using the propensity-score matched cohort. We found similar results irrespective of patient sex, age, race, or the presence of diabetes, peripheral vascular disease or heart failure. CONCLUSION: Although overall survival rates were low, IMA was associated with lower risk of mortality and cardiovascular morbidity compared to SVG in patients on dialysis.

Potential cost-effectiveness of prophylactic use of the implantable cardioverter defibrillator or amiodarone after myocardial infarction.

BACKGROUND: Clinical trials have shown that implantable cardioverter defibrillators (ICDs) improve survival in patients with sustained ventricular arrhythmias. OBJECTIVE: To determine the efficacy necessary to make prophylactic ICD or amiodarone therapy cost-effective in patients with myocardial infarction. DESIGN: Markov model-based cost utility analysis. DATA SOURCES: Survival, cardiac death, and inpatient costs were estimated on the basis of the Myocardial Infarction Triage and Intervention registry. Other data were derived from the literature. TARGET POPULATION: Patients with past myocardial infarction who did not have sustained ventricular arrhythmia. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: ICD or amiodarone compared with no treatment. OUTCOME MEASURES: Life-years, quality-adjusted life-years (QALYs), costs, number needed to treat, and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Compared with no treatment, ICD use led to the greatest QALYs and the highest expenditures. Amiodarone use resulted in intermediate QALYs and costs. To obtain acceptable cost-effectiveness thresholds (

The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis.

OBJECTIVES: This study was designed to compare the prognostic value of an abnormal troponin level derived from studies of patients with non-ST elevation acute coronary syndromes (ACS). BACKGROUND: Risk stratification for patients with suspected ACS is important for determining need for hospitalization and intensity of treatment. METHODS: We identified clinical trials and cohort studies of consecutive patients with suspected ACS without ST-elevation from 1966 through 1999. We excluded studies limited to patients with acute myocardial infarction and studies not reporting mortality or troponin results. RESULTS: Seven clinical trials and 19 cohort studies reported data for 5,360 patients with a troponin T test and 6,603 with a troponin I test. Patients with positive troponin (I or T) had significantly higher mortality than those with a negative test (5.2% vs. 1.6%, odds ratio [OR] 3.1). Cohort studies demonstrated a greater difference in mortality between patients with a positive versus negative troponin I (8.4% vs. 0.7%, OR 8.5) than clinical trials (4.8% if positive, 2.1% if negative, OR 2.6, p = 0.01). Prognostic value of a positive troponin T was also slightly greater for cohort studies (11.6% mortality if positive, 1.7% if negative, OR 5.1) than for clinical trials (3.8% if positive, 1.3% if negative, OR 3.0, p = 0.2) CONCLUSIONS: In patients with non-ST elevation ACS, the short-term odds of death are increased three- to eightfold for patients with an abnormal troponin test. Data from clinical trials suggest a lower prognostic value for troponin than do data from cohort studies.

The incidence of unrecognized myocardial infarction in women with coronary heart disease.

BACKGROUND: Several cohort studies in populations without coronary heart disease have demonstrated that up to 40% of incident myocardial infarctions are clinically unrecognized. OBJECTIVE: To determine the incidence of unrecognized myocardial infarction in women with coronary heart disease in the Heart and Estrogen/progestin Replacement Study (HERS). DESIGN: Randomized, double-blind, placebo-controlled trial of conjugated estrogens plus medroxyprogesterone or identical placebo with 4.1 years of follow-up. SETTINGS: Outpatient and community settings at 20 U.S. clinical centers. PATIENTS: 2763 postmenopausal women younger than 80 years of age with coronary heart disease and an intact uterus. MEASUREMENTS: Annual electrocardiograms were obtained for all participants during follow-up (mean, 4.1 years) and were evaluated by using the NOVACODE computer algorithm and visual confirmation. A total of 13 715 electrocardiograms were obtained. Suspected unrecognized myocardial infarctions were investigated by comparing a participant's previous surveillance electrocardiograms with the electrocardiograms obtained from all of her intervening hospitalizations. Characteristics of patients with recognized and unrecognized myocardial infarction were compared. RESULTS: Among the 256 nonfatal myocardial infarctions, 11 were unrecognized (4.3% [95% CI, 2.2% to 7.6%]). Seven occurred in women assigned to placebo and 4 occurred in women assigned to hormone therapy (P > 0.2). Women with unrecognized myocardial infarction were less likely to have diabetes mellitus or previous angina and were more likely to have had previous bypass surgery compared with women who had clinically recognized myocardial infarction. CONCLUSION: The incidence of unrecognized myocardial infarction in women with coronary disease was far lower than that observed in previous studies of populations without coronary heart disease.

Outcomes of noncardiac surgery after coronary bypass surgery or coronary angioplasty in the Bypass Angioplasty Revascularization Investigation (BARI).

PURPOSE: Previous studies have shown that coronary artery bypass surgery reduces the risk of cardiac complications after noncardiac surgery. Whether coronary angioplasty provides equivalent protection is not known. SUBJECTS AND METHODS: Patients were randomly assigned to undergo cardiac artery bypass surgery or angioplasty as part of the Bypass Angioplasty Revascularization Investigation trial. All subsequent noncardiac surgeries during a mean (+/- SD) follow-up of 7.7 years were recorded among participants in the ancillary Study of Economics and Quality of Life. Rates of mortality and nonfatal myocardial infarction, length of stay, and hospital costs were compared by the original randomized assignment. RESULTS: A total of 501 patients had noncardiac surgery at a median of 29 months after their most recent coronary revascularization procedure. Mortality and nonfatal myocardial infarction within 30 days of the first noncardiac surgery occurred in 4 of the 250 of the surgery-assigned patients and in 4 of the 251 of the angioplasty-assigned patients (P = 1.0). There were no significant differences in the mean length of hospital stay (6.3 +/- 6.7 versus 6.2 +/- 6.8 days; P = 0.47) or hospital cost ($8,920 +/- $11,511 versus $7,785 +/- $7,643; P = 0.33) between the surgery and angioplasty groups. Similar results were obtained when subsequent noncardiac procedures were included in the analysis. CONCLUSION: Rates of myocardial infarction and death after noncardiac surgery are similarly low after contemporary bypass surgery or angioplasty in patients with multivessel coronary artery disease.

Cost-effectiveness of radiofrequency ablation for supraventricular tachycardia.

BACKGROUND: Radiofrequency ablation is an established but expensive treatment option for many forms of supraventricular tachycardia. Most cases of supraventricular tachycardia are not life-threatening; the goal of therapy is therefore to improve the patient's quality of life. OBJECTIVE: To compare the cost-effectiveness of radiofrequency ablation with that of medical management of supraventricular tachycardia. DESIGN: Markov model. DATA SOURCES: Costs were estimated from a major academic hospital and the literature, and treatment efficacy was estimated from reports from clinical studies at major medical centers. Probabilities of clinical outcomes were estimated from the literature. To account for the effect of radiofrequency ablation on quality of life, assessments by patients who had undergone the procedure were used. TARGET POPULATION: Cohort of symptomatic patients who experienced 4.6 unscheduled visits per year to an emergency department or a physician's office while receiving long-term drug therapy for supraventricular tachycardia. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Initial radiofrequency ablation, long-term antiarrhythmic drug therapy, and treatment of acute episodes of arrhythmia with antiarrhythmic drugs. OUTCOME MEASURES: Costs, quality-adjusted life-years, life-years, and marginal cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Among patients who have monthly episodes of supraventricular tachycardia, radiofrequency ablation was the most effective and least expensive therapy and therefore dominated the drug therapy options. Radiofrequency ablation improved quality-adjusted life expectancy by 3.10 quality-adjusted life-years and reduced lifetime medical expenditures by $27 900 compared with long-term drug therapy. Long-term drug therapy was more effective and had lower costs than episodic drug therapy. RESULTS OF SENSITIVITY ANALYSIS: The findings were highly robust over substantial variations in assumptions about the efficacy and complication rate of radiofrequency ablation, including analyses in which the complication rate was tripled and efficacy was decreased substantially. CONCLUSIONS: Radiofrequency ablation substantially improves quality of life and reduces costs when it is used to treat highly symptomatic patients. Although the benefit of radiofrequency ablation has not been studied in less symptomatic patients, a small improvement in quality of life is sufficient to give preference to radiofrequency ablation over drug therapy.

Quality of life after coronary revascularization in the United States and Canada.

Cardiac procedures are performed less frequently in Canada than in the United States (US), yet rates of cardiac death and myocardial infarction are similar. We therefore sought to compare long-term symptoms and quality of life in Canadian and American patients undergoing initial coronary revascularization. The 161 patients enrolled in the Bypass Angioplasty Revascularization Investigation at the Montreal Heart Institute were compared with 934 patients enrolled at 7 US sites. Patients' outcomes were documented for 5 years after random assignment to percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Functional status was assessed using the Duke Activity Status Index. Canadian patients were significantly younger and had more angina at study entry. Death and nonfatal myocardial infarction were not significantly different between Canadian and US patients after adjustment for baseline risk. Canadian patients had significantly greater improvements in functional status at 1-year follow-up (Duke Activity Status Index score + 13.5 vs. + 6.0, p = 0.002), but this difference progressively narrowed over 5 years. Angina was equally prevalent in Canadian and US patients at 1 year (16% vs. 19%), but significantly more prevalent in Canadian patients at 5 years (36% vs. 16%, p = 0.001). Repeat revascularization procedures were performed less often over 5 years among Canadian patients (26% vs. 34%, p = 0.08), especially coronary artery bypass graft surgery after initial percutaneous transluminal coronary angioplasty (18% vs. 32%, p = 0.03). These results suggest more anginal symptoms are required in Canada before coronary revascularization, but as a result Canadians receive greater improvements in quality of life after the procedure.

Projected long-term costs of coronary stenting in multivessel coronary disease based on the experience of the Bypass Angioplasty Revascularization Investigation (BARI).

BACKGROUND: Stents are now used in the majority of percutaneous coronary revascularization procedures. It is not clear whether the higher initial cost of stenting is later repaid by reducing costly complications and repeat revascularization procedures, especially for patients with multivessel disease. METHODS: To project the long-term costs of using coronary stents, angioplasty, or bypass surgery to treat patients with multivessel coronary artery disease, we developed a decision model based on the outcomes documented in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We studied 2 clinical strategies: provisional stenting of suboptimal PTCA results and primary stenting of all angiographically eligible lesions. The cost of CABG was also updated to reflect contemporary practice. RESULTS: Provisional stenting had lower projected costs over a 4-year period than either traditional PTCA (-$1742, or -3.4%) or contemporary CABG (-$832, or -1.7%), mostly because of reductions in emergency CABG after PTCA. In contrast, primary stenting had higher projected costs over a 4-year period than either PTCA (+$333, or +0. 7%) or contemporary CABG (+$1243, or +2.5%), mainly because of the higher initial procedure costs. These results were not substantially altered when we systematically varied the key parameters of the models in 1-way and 2-way sensitivity analyses. CONCLUSIONS: A primary stenting strategy in patients with multivessel disease has higher projected long-term costs than CABG. In contrast, a provisional stenting strategy in multivessel disease has lower projected costs than either PTCA or CABG.

Clustering and the design of preference-assessment surveys in healthcare.

OBJECTIVE: To show cluster analysis as a potentially useful tool in defining common outcomes empirically and in facilitating the assessment of preferences for health states. DATA SOURCES: A survey of 224 patients with ventricular arrhythmias treated at Kaiser Permanente of Northern California. STUDY DESIGN/METHODS: Physical functioning was measured using the Duke Activity Status Index (DASI), and mental status and vitality using the Medical Outcomes Study Short Form-36 items (SF-36). A "k-means" clustering algorithm was used to identify prototypical health states, in which patients in the same cluster shared similar responses to items in the survey. PRINCIPAL FINDINGS: The clustering algorithm yielded four prototypical health states. Cluster 1 (21 percent of patients) was characterized by high scores on physical functioning, vitality, and mental health. Cluster 2 (33 percent of patients) had low physical function but high scores on vitality and mental health. Cluster 3 (29 percent of patients) had low physical function and low vitality but preserved mental health. Cluster 4 (17 percent of patients) had low scores on all scales. These clusters served as the basis of written descriptions of the health states. CONCLUSIONS: Employing a clustering algorithm to analyze health status survey data enables researchers to gain a data-driven, concise summary of the experiences of patients.

Quality of life before and after radiofrequency catheter ablation in patients with drug refractory atrioventricular nodal reentrant tachycardia.

In a retrospective survey of 161 highly symptomatic patients, we found significant improvements in symptoms, patient utility, and use of medical care services after radiofrequency ablation for atrioventricular nodal reentrant tachycardia.

Clinical correlates of the initial and long-term cost of coronary bypass surgery and coronary angioplasty.

BACKGROUND: Medical costs vary substantially among patients. Understanding the baseline factors that predict subsequent cost may allow better selection of therapy for individual patients. Understanding the postprocedure events that increase cost should help to improve efficiency and effectiveness of coronary revascularization. METHODS: Data on 4-year costs were collected from patients randomly assigned to coronary angioplasty or bypass surgery as part of the BARI (Bypass Angioplasty Revascularization Investigation) trial. Regression models first examined factors known at the time of randomization that prospectively predicted initial procedure cost and long-term cost. Subsequent models tested the value of postrandomization events as explanatory variables for cost. RESULTS: The independent baseline predictors of higher initial percutaneous transluminal coronary angioplasty cost included 3-vessel disease (+12%) and acute presentations (+22%), whereas the independent predictors of higher initial coronary artery bypass grafting cost included the number of comorbid conditions (+5% per condition) and female sex (+7%). The independent baseline predictors of 4-year cost included heart failure (+26%), diabetes (+22%), comorbidity (+10%), and angioplasty assignment in patients with 2-vessel disease (-15%). Postrandomization models showed higher initial and long-term costs were strongly correlated with the number of repeat revascularization procedures (+30% to +128%) and the occurrence of clinical complications (+8% to +131%). CONCLUSIONS: Two-vessel disease identifies patients likely to have lower costs after angioplasty, whereas heart failure, comorbid conditions, and diabetes identify patients likely to accrue higher costs after either angioplasty or bypass surgery. Long-term costs can be potentially reduced by interventions that decrease procedural complications or reduce the need for repeat revascularization.

Meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitrates for stable angina.

CONTEXT: Which drug is most effective as a first-line treatment for stable angina is not known. OBJECTIVE: To compare the relative efficacy and tolerability of treatment with beta-blockers, calcium antagonists, and long-acting nitrates for patients who have stable angina. DATA SOURCES: We identified English-language studies published between 1966 and 1997 by searching the MEDLINE and EMBASE databases and reviewing the bibliographies of identified articles to locate additional relevant studies. STUDY SELECTION: Randomized or crossover studies comparing antianginal drugs from 2 or 3 different classes (beta-blockers, calcium antagonists, and long-acting nitrates) lasting at least 1 week were reviewed. Studies were selected if they reported at least 1 of the following outcomes: cardiac death, myocardial infarction, study withdrawal due to adverse events, angina frequency, nitroglycerin use, or exercise duration. Ninety (63%) of 143 identified studies met the inclusion criteria. DATA EXTRACTION: Two independent reviewers extracted data from selected articles, settling any differences by consensus. Outcome data were extracted a third time by 1 of the investigators. We combined results using odds ratios (ORs) for discrete data and mean differences for continuous data. Studies of calcium antagonists were grouped by duration and type of drug (nifedipine vs nonnifedipine). DATA SYNTHESIS: Rates of cardiac death and myocardial infarction were not significantly different for treatment with beta-blockers vs calcium antagonists (OR, 0.97; 95% confidence interval [CI], 0.67-1.38; P = .79). There were 0.31 (95% CI, 0.00-0.62; P = .05) fewer episodes of angina per week with beta-blockers than with calcium antagonists. beta-Blockers were discontinued because of adverse events less often than were calcium antagonists (OR, 0.72; 95% CI, 0.60-0.86; P<.001). The differences between beta-blockers and calcium antagonists were most striking for nifedipine (OR for adverse events with beta-blockers vs nifedipine, 0.60; 95% CI, 0.47-0.77). Too few trials compared nitrates with calcium antagonists or beta-blockers to draw firm conclusions about relative efficacy. CONCLUSIONS: beta-Blockers provide similar clinical outcomes and are associated with fewer adverse events than calcium antagonists in randomized trials of patients who have stable angina.