The dollars and sense of drug-eluting stents.
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
James M Brophy
Publications and source records attributed to James M Brophy.
Fluctuating inflammatory markers in patients with stable ischemic heart disease.
BACKGROUND: C-reactive protein (CRP), a marker of inflammation, is increasingly measured to stratify coronary artery disease risk and guide clinical management. However, little is known about how inflammatory markers fluctuate over time in patients with stable ischemic heart disease. METHODS: We examined serial serum CRP values in 159 patients with histories spanning the clinical spectrum of ischemic heart disease. Two to 8 CRP measurements were made at intervals varying from 15 days to 6 years. Successive interleukin (IL)-6 values were examined in 1 subgroup. Blood samples were always taken when patients were clinically stable, in the absence of any potentially confounding inflammatory condition. RESULTS: C-reactive protein values in individual patients fluctuated considerably when examined in the following ranges: less than 1 mg/L, 1 to 3 mg/L, and greater than 3 mg/L, proposed to indicate low, average, and high risk. Sixty-four patients (40.3%) changed risk category between the first and the second measurement. Within-patient variances of CRP and IL-6 levels were 1.79 mg/L (95% confidence interval, 1.60-2.00) and 2.69 pg/mL (95% confidence interval, 2.29-3.18), respectively. The variability of CRP was consistent over different times and across clinical groups, and independent of body mass index, smoking status, medication, and clinical events. CONCLUSIONS: Relatively important fluctuations in CRP levels in patients with stable ischemic heart disease may be problematic for risk stratification and treatment monitoring. A similar IL-6 variability suggests that these patients have a dynamic inflammatory status whose kinetics may modulate acute coronary risk.
Aged↗
The benefit of cholesterol-lowering medications after coronary revascularization: a population study.
BACKGROUND: In clinical trials, cholesterol-lowering medications have been proven to decrease mortality and morbidity and are strongly recommended as secondary prevention in patients with established coronary artery disease. In routine practice, the translation of these benefits to elderly patients with recent coronary revascularization is less well known. METHODS: Using the provincial computerized administrative databases of the Régie de l'Assurance Maladie du Québec, we identified all elderly patients (>65 years old) in Quebec, Canada, discharged alive after a coronary revascularization procedure (percutaneous coronary intervention or coronary artery bypass graft) between April 1, 1995, and December 31, 1997, and determined the percentage fulfilling prescriptions for cholesterol-lowering drug therapy. Time-dependent multivariable models examined the clinical end points of total mortality, acute myocardial infarctions, and repeat coronary revascularizations as a function of cholesterol-lowering drug exposure. Patients were followed up until death or December 31, 1999. RESULTS: We identified 11958 elderly patients who had a coronary revascularization between April 1, 1995, and December 31, 1997. During an average 3-year follow-up, users of cholesterol-lowering medications had a decreased risk of death [hazard ratio (HR) 0.66, 95% CI 0.45-0.96] or myocardial infarction (HR 0.77, 95% CI 0.54-1.11) but no reduction in repeat revascularizations (HR 1.06, 95% CI 0.88-1.28). CONCLUSIONS: In this population-based study of recently revascularized elderly patients, we observed health benefits associated with the use of cholesterol-lowering medications of similar size to those seen in randomized clinical trials. The translation of these benefits from clinical trials to a nonselected population of revascularized patients emphasizes the importance of this aspect of secondary prevention in clinical practice.
Aged↗
Cost-effectiveness of drug-eluting coronary stents in Quebec, Canada.
OBJECTIVES: The aim of this investigation was to assess the incremental cost-effectiveness of replacing bare metal coronary stents (BMS) with drug-eluting stents (DES) in the Province of Quebec, Canada. METHODS: The strategy used was a cost-effectiveness analysis from the perspective of the health-care provider, in the province of Quebec, Canada (population 7.5 million). The main outcome measure was the cost per avoided revascularization intervention. RESULTS: Based on the annual Quebec rate of 14,000 angioplasties with an average of 1.7 stents per procedure and a purchase cost of $2,600 Canadian dollar (CDN) for DES, 100 percent substitution of BMS with DES would require an additional $45.1 million CDN of funding. After the benefits of reduced repeat revascularization interventions are included, the incremental cost would be $35.2 million CDN. The cost per avoided revascularization intervention (18 percent coronary artery bypass graft, 82 percent percutaneous coronary intervention [PCI]) would be $23,067 CDN. If DES were offered selectively to higher risk populations, for example, a 20 percent subgroup with a relative restenosis risk of 2.5 times the current bare metal rate, the incremental cost of the program would be $4.9 million CDN at a cost of $7,800 per avoided revascularization procedure. Break-even costs for the program would occur at DES purchase cost of $1,161 for 100 percent DES use and $1,627 for selective 20 percent DES use for high-risk patients for restenosis (RR = 2.5). Univariate and Monte Carlo sensitivity analyses indicate that the parameters most affecting the analysis are the capacity to select patients at high risk of restenosis, the average number of stents used per PCI, baseline restenosis rates for BMS, the effectiveness ratio of restenosis prevention for DES versus BMS, the cost of DES, and the revascularization rate after initial PCI. Sensitivity analyses suggest little additional health benefits but escalating cost-effectiveness ratios once a DES penetration of 40 percent has been attained. CONCLUSIONS: Under current conditions in Quebec, Canada, selective use of DES in high-risk patients is the most acceptable strategy in terms of cost-effectiveness. Results of such an analysis would be expected to be similar in other countries with key model parameters similar to those used in this model. This model provides an example of how to evaluate the cost-effectiveness of selective use of a new technology in high-risk patients.
Antineoplastic Agents↗
Celecoxib and cardiovascular risks.
In a very short time, COX-2 enzyme inhibitors have gone from the darlings to the pariahs of the pharmaceutical industry. These drugs were developed based on the hypothesis whereby selective inhibition of the COX enzyme would lead to reduction in pain and inflammation without associated gastrointestinal and bleeding risks. However, in September 2004, rofecoxib was voluntarily removed from the market for increased cardiovascular risk and in April 2005, valdecoxib was also withdrawn, at least in part, due to excess cardiovascular risk. Celecoxib was the first COX-2 inhibitor introduced and the only remaining one on the US market. There is consequently a justified concern that cardiovascular toxicity is a class effect of all COX-2 inhibitors. This article systematically reviews the evidence surrounding COX-2 inhibitors and cardiovascular risk. Although the evidence suggests a fairly consistent cardiovascular risk with rofecoxib, the evidence for cardiovascular risk with celecoxib is more equivocal. Although isolated studies have suggested some cardiovascular risk for celecoxib, the totality of the evidence suggests that any risk is likely to be small and comparable to traditional NSAIDs. The cardiovascular risks of COX-2 inhibitors appear heterogeneous, influenced not only by the drug class, but also individual drug, dosage and patient characteristics. Specific modifying factors of the cardiovascular risk of COX-2 inhibitors including dose, concomitant drugs, individual cardiac and genetic risk profiles, will require further study.
Cardiovascular Diseases↗
Friendly fire and continuing medical education.
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Education, Medical, Continuing↗
End-user involvement in health technology assessment (HTA) development: a way to increase impact.
OBJECTIVES: A mechanism to increase the influence of Health Technology Assessments (HTAs) on hospital policy decisions was developed. METHODS: We describe the process and results of an experiment in which a local in-hospital HTA unit was created to provide sound evidence on technology acquisition issues, and to formulate locally appropriate policy recommendations. The Unit consists of a small technical staff that accesses and synthesizes the evidence incorporating local health and economic data, and a Policy Committee that develops policy recommendations based on this evidence. It represents administration, health-care professionals, patients, and representatives of the clinical disciplines affected by each issue. The level of success of the Unit was independently evaluated. RESULTS: To date, 16 reports have been completed, each within 2-4 months. Five recommended unrestricted use, seven recommended rejection, and four recommended very limited use of the technology in question. All have been incorporated into hospital policy. Budget impact is estimated at approximately 3 million dollars of savings per year. CONCLUSIONS: This local in-house HTA agency has had a major impact on the adoption of new technology. Probable reasons for success are (i) relevance (selection of topics by administration with on-site production of HTAs allowing them to incorporate local data and reflect local needs), (ii) timeliness, and (iii) formulation of policy reflecting community values by a local representative committee. Because over one third of all health-care costs are incurred in the hospital, diffusion of this model could have a significant effect on the quantity and quality of health-care spending.
Budgets↗
Primary angioplasty and thrombolysis are both reasonable options in acute myocardial infarction.
Primary angioplasty is increasingly being advocated as the preferred approach for treating acute ST-segment elevation myocardial infarction regardless of whether interinstitutional transfer is required. This review critically analyzes the evidence comparing primary angioplasty with thrombolytic therapy and concludes that reasonable health care professionals may still find considerable uncertainty about the superiority of primary angioplasty for all situations. The magnitude of benefit for primary angioplasty over thrombolysis is probably less than 1 to 2 lives saved/100 patients treated and largely depends on the choice of thrombolytic agent, time to treatment, place of treatment, and adjunctive therapy. There is little evidence that systematically transferring patients for primary angioplasty in routine practice will provide any health benefits over thrombolysis. Consequently, it may be most useful to view these treatments as complementary rather than competitive. Thrombolysis remains a clinically and economically attractive option for the treatment of acute myocardial infarction that does not require the radical restructuring of our health care systems.
Angioplasty, Balloon, Coronary↗
Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: a randomized placebo-controlled study.
BACKGROUND: The impact of cyclooxygenase (COX)-2 antagonist treatment on acute coronary risk is controversial. We investigated the effect of prolonged COX-2 inhibition on inflammatory profile and endothelial function in patients with ischemic heart disease and high serum C-reactive protein (CRP) values. METHODS AND RESULTS: In a double-blind study, 35 stable subjects on low-dose aspirin with > or =2 previous acute coronary events and 2 of 2 screening CRP values >2.0 mg/L were randomized to the COX-2 inhibitor rofecoxib (25 mg) or placebo daily for 6 months. Serum CRP, interleukin-6 (IL-6), P-selectin, matrix metalloproteinase-9 (MMP-9), and brachial artery endothelial function were evaluated. In the placebo group, CRP (median) was 3.16 mg/L (25% and 75% quartiles, 1.90 and 5.78 mg/L) at baseline and 4.22 mg/L (25% and 75% quartiles, 2.04 and 6.25 mg/L) at 6 months; in the rofecoxib group, CRP was 3.45 mg/L (25% and 75% quartiles, 2.08 and 5.78 mg/L) at baseline and 1.41 mg/L (25% and 75% quartiles, 1.17 and 4.81 mg/L) at 6 months (P=0.03). Rofecoxib compared with placebo also lowered IL-6 at 6 months (P=0.0002). There was a significant off-drug effect on CRP and IL-6 levels in the rofecoxib group 3 months after treatment (P=0.005 and P=0.009, respectively). Rofecoxib did not significantly affect P-selectin, MMP-9, and brachial artery vasoreactivity. CONCLUSIONS: Prolonged COX-2 inhibition attenuates CRP and IL-6, does not modify P-selectin and MMP-9, and has no deleterious effect on endothelial function in stable patients with a history of recurrent acute coronary events and raised CRP. These results strengthen the rationale for evaluating the clinical benefit of COX-2 inhibition in patients with ischemic heart disease.
Anti-Inflammatory Agents, Non-Steroidal↗
Primary angioplasty or thrombolysis? A topical parable.
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Angioplasty, Balloon, Coronary↗
A multivariate model for predicting mortality in patients with heart failure and systolic dysfunction.
BACKGROUND: Heart failure is a leading cause of morbidity and mortality, but there are no reliable models based on readily available clinical variables to predict outcomes in patients taking angiotensin-converting enzyme (ACE) inhibitors. METHODS: A multivariate statistical model to predict mortality was developed in a random sample (n = 4277 patients [67%]) of the 6422 patients enrolled in the Digitalis Investigation Group trial who had a depressed ejection fraction (<or=45%), were in sinus rhythm, and were taking ACE inhibitors. The model was then validated in the remaining 2145 patients. RESULTS: Total mortality in the derivation sample was 11.2% (n = 480) at 12 months and 29.9% (n = 1277) at 36 months. Lower ejection fraction, worse renal function, cardiomegaly, worse functional class, signs or symptoms of heart failure, lower blood pressure, and lower body mass index were associated with reduced 12-month survival. This model provided good predictions of mortality in the verification sample. The same variables, along with age and the baseline use of nitrates, were also predictive of 36-month mortality. CONCLUSION: Routine clinical variables can be used to predict short- and long-term mortality in patients with heart failure and systolic dysfunction who are treated with ACE inhibitors.
Aged↗
Geographical variations in post myocardial infarction mortality and their impact on risk selection.
OBJECTIVES: The objective is to assess the impact of geographical variations in mortality on risk selection in patients after acute myocardial infarction. METHOD: Mortality analysis is used with an actuarial methodology applied to follow-up studies based on data from randomized clinical trial and observational cohort studies of acute myocardial infarction patients from different geographic areas. Observed mortality was calculated as geometric average annual rate (q) and compared to the expected geometric average annual mortality (q') mortality calculated from different life tables. This comparison was expressed as mortality ratios (MR). Values of q and MR were averaged within each country grouping. Variance, standard deviation, and variation coefficient (CV) were calculated. RESULTS: Geometric average annual mortality rates varied by country. The lowest rate (2.7%) was observed in Japan, and the highest rates (7.5%) were seen in studies from the United Kingdom and Northern Europe (Denmark, Sweden, Finland). The average annual mortality rate was 4.9%. Mortality ratios averaged within countries vary from 182% to 212%, with an overall average value of 198%. Coefficient of variation (CV) was 36% for geometric average annual mortality rates and 6% for mortality ratios. CONCLUSION: Although annual mortality rates from all causes vary greatly between countries, mortality ratios do not vary and remain relatively constant. This highlights the interest of risk assessment using mortality analysis methodology, which makes the geographic variation in post-myocardial infarction mortality disappear.
Developed Countries↗
The use of cholesterol-lowering medications after coronary revascularization.
BACKGROUND: In clinical trials, cholesterol-lowering medications have been proven to decrease mortality and morbidity and are strongly recommended as secondary prevention for patients with established coronary artery disease. Whether physicians and patients follow this recommendation is unknown. Our objective was to determine the rate at which patients fill at least one prescription for cholesterol-lowering medications after coronary revascularization. METHODS: Using the computerized administrative databases of the Régie de l'assurance maladie du Québec, we identified all elderly patients (older than 65 years) who had a coronary revascularization procedure (percutaneous coronary intervention or coronary artery bypass graft) between Apr. 1, 1995, and Dec. 31, 1997, and who survived until hospital discharge. We also determined the percentage of these patients who filled one or more prescriptions for cholesterol-lowering drug therapy before Dec. 31, 1999, or death, whichever date came first. We used multivariate logistic regression models to examine the independent associations between filling a prescription for a cholesterol-lowering drug, patient characteristics and the type and year of coronary revascularization. RESULTS: We identified 11 958 elderly patients who had a coronary revascularization between Apr. 1, 1995, and Dec. 31, 1997. During a follow-up period that averaged 3 years, 4443 (37.2%) patients did not fill a prescription for a cholesterol-lowering medication. Patients who were male, of advanced age, who had diabetes or congestive heart failure were less likely to fill a prescription for a cholesterol-lowering medication. Patients whose initial revascularization procedure was coronary artery bypass grafting were also less likely than those who had angioplasty to start cholesterol-lowering medication (relative risk [RR] 0.77, 95% confidence interval [CI] 0.73 - 0.81). Use of cholesterol lowering medications before the revascularization procedure was very strongly associated with future drug use (RR 7.20, 95% CI 6.83-7.58). INTERPRETATION: In this population-based study of revascularized patients, we observed a substantial underutilization of cholesterol-lowering medications after revascularization. Our observations suggest an important role for continuity of care in the treatment of cardiovascular patients undergoing revascularization procedures.
Aged↗
Evidence for use of coronary stents. A hierarchical bayesian meta-analysis.
BACKGROUND: Coronary stents are widely used in interventional cardiology, but a current quantitative systematic overview comparing routine coronary stenting with standard percutaneous transluminal coronary angioplasty (PTCA) and restricted stenting (provisional stenting) has not been published. PURPOSE: To summarize results from all randomized clinical trials comparing routine coronary stenting with standard PTCA. DATA SOURCES: Electronic databases were searched by using the key words angioplasty and stent. References from identified articles were also reviewed. In addition, several prominent general medical and cardiology journals were searched and agencies known to perform systematic reviews were consulted. STUDY SELECTION: All comparative randomized clinical trials were included, except those involving primary angioplasty for the treatment of acute myocardial infarction. DATA EXTRACTION: A specified protocol was followed, and two of the authors independently extracted the data. Outcomes assessed were total mortality, myocardial infarction, angiographic restenosis, coronary artery bypass surgery, repeated PTCA, and freedom from angina. DATA SYNTHESIS: The results were synthesized by using a Bayesian hierarchical random-effects model. A total of 29 trials involving 9918 patients were identified. There was no evidence for a difference between routine coronary stenting and standard PTCA in terms of deaths or myocardial infarctions (odds ratio, 0.90 [95% credible interval [CrI], 0.72 to 1.11]) or the need for coronary artery bypass surgery (odds ratio, 1.01 [CrI, 0.79 to 1.31]). Coronary stenting reduced the rate of restenosis (odds ratio, 0.52 [CrI, 0.37 to 0.69]) and the need for repeated PTCA (odds ratio, 0.59 [CrI, 0.50 to 0.68]). The trials showed a wide range of crossover rates from PTCA to stenting. By use of a multiplicative model, each 10% increase in crossover rate decreased the need for repeated angioplasty by approximately 8% (odds ratio multiplying factor, 1.08 [CrI, 0.98 to 1.18]). Routine stenting probably reduces the need for repeated angioplasty by fewer than 4 to 5 per 100 treated persons compared with PTCA with provisional stenting. Studies were not blinded and suggest a bias with a possible overestimation of this benefit. CONCLUSIONS: In the controlled environment of randomized clinical trials, routine coronary stenting is safe but probably not associated with important reductions in rates of mortality, acute myocardial infarction, or coronary artery bypass surgery compared with standard PTCA with provisional stenting. Coronary stenting is associated with substantial reductions in angiographic restenosis rates and the subsequent need for repeated PTCA, although this benefit may be overestimated because of trial designs. The incremental benefit of routine stenting for reducing repeated angioplasty diminishes as the crossover rate of stenting with conventional PTCA increases.
Aged↗
A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents.
BACKGROUND: Drug-eluting stents (DES) are associated with lower restenosis rates than bare-metal stents (BMS), but the benefits and safety of the new devices have not been systematically quantified across different trials. We undertook a meta-analysis of randomised trials comparing BMS and stents eluting sirolimus or paclitaxel. METHODS: A systematic literature search aimed to identify all randomised clinical trials with 6-12 months of clinical follow-up. Results were pooled by a hierarchical Bayesian random-effects model with prespecified stratification for drug and the presence of carrier polymer. The primary outcomes examined were rates of death, myocardial infarction, target-lesion revascularisation, major adverse cardiac events (death, myocardial infarction, and target-vessel revascularisation), and angiographic restenosis. FINDINGS: We identified 11 eligible trials involving 5103 patients. The pooled mortality rates were low for both DES and BMS with no evidence of any difference between them (odds ratio 1.11 [95% credible interval 0.61-2.06]). Pooled rates of myocardial infarction showed no between-group difference (0.92 [0.65-1.25]). The rate of major adverse cardiac events was 7.8% with DES and 16.4% with BMS (0.42 [0.32-0.53]), and the angiographic restenosis rates were also lower for DES (8.9% vs 29.3%; 0.18 [0.06-0.40]). The pooled rates of major adverse cardiac events for each DES type and the respective BMS were: for sirolimus, 6.8% versus 21.0% (0.28 [0.17-0.41]); for polymer-based paclitaxel 8.7% versus 16.7% (0.47 [0.25-0.71]); and for non-polymer-based paclitaxel 7.7% versus 9.5% (0.64 [0.42-1.00]). We did not observe higher rates of edge restenosis, stent thrombosis, or late incomplete stent apposition with DES, although the credible intervals were wide. INTERPRETATION: Sirolimus-eluting and polymeric paclitaxel-eluting stents are effective at decreasing rates of angiographic restenosis and major adverse cardiac events compared with BMS. However, there is no evidence that they affect mortality or myocardial-infarction rates. They also appear to be safe in the short to medium term, although definitive conclusions are not possible. Larger studies with longer follow-up are needed to define better the role of these new devices.
Angioplasty, Balloon, Coronary↗
GRACIA: implications for clinical practice.
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Angioplasty, Balloon, Coronary↗
Medical decision making with incomplete evidence--choosing a platelet glycoprotein IIbIIIa receptor inhibitor for percutaneous coronary interventions.
BACKGROUND: Medical decision making must often be performed despite incomplete evidence. An example is the choice of a glycoprotein IIb/IIIa (GP2b3a) inhibitor, a class of potent antiplatelet medications, as adjunctive therapy during percutaneous coronary interventions (PCIs). GP2b3a inhibitor efficacy in reducing adverse outcomes has been well documented with multiple placebo-controlled randomized trials, but there is a paucity of comparative data about their individual equivalency. Substantial cost differentials are also present between the drugs. METHODS: A systematic review of the literature was performed to identify all randomized placebo-controlled trials of GP2b3a inhibitors as adjunctive therapy for PCI. Three complimentary methods were used to assist in decision making regarding drug equivalency. First, the data from the single direct comparative trial are analyzed from a Bayesian perspective. Next, prior information from other GP2b3a inhibitor trials in similar but not identical patient populations is incorporated. In the 3rd method, indirect comparisons of GP2b3a inhibitors are carried out using a hierarchical meta-analytic model of the placebo-controlled trials identified by the systematic review. RESULTS: A total of 12 randomized trials were identified involving 3 agents (abciximab, eptifibatide, tirofiban), but only 1 involved a direct comparison of 2 drugs (abciximab v. tirofiban). In contradiction to the original publication, the authors' Bayesian analysis both without (method 1) and with (method 2) the inclusion of some prior information suggests a reasonable probability of equivalency. The indirect comparisons from all randomized placebo-controlled trials (method 3) also failed to provide support for superiority of any agent over the others. CONCLUSION: Decision making with incomplete evidence is a difficult but frequently occurring medical dilemma. The authors propose 3 methods that may elucidate the process and illustrate them in the context of the choice of GP2b3a inhibitor for adjunctive therapy during PCI. Further data may or may not eventually lead to a different conclusion, but based on the evidence available to date, the authors' 3 methods suggest clinical equivalency between GP2b3a inhibitors, in contrast to the initial conclusions from the single comparative randomized trial.
Angioplasty, Balloon, Coronary↗