Much of the cost of medical care in the population is generated by the management of patients with chronic illnesses such as coronary disease and diabetes. Effective treatments for chronic diseases may increase overall medical costs, even after accounting for subsequent savings due to prevention of costly complications. These higher net costs may be acceptable, however, if clinical outcomes are sufficiently improved. The assessment of the value provided by treatments therefore requires measuring both their clinical and economic consequences, and weighing these outcomes to assess their cost-effectiveness compared with alternative treatments.
In this study, we found that prompt coronary revascularization was significantly more costly than medical therapy for patients who have coronary disease and diabetes. The high initial procedural costs of CABG and PCI were only partially offset by later cost savings over four years of follow-up, a finding consistent with previous studies. The cost-effectiveness of coronary revascularization in the BARI 2D patient population was more difficult to assess owing to the limited duration of follow-up (four years) compared with the projected life-expectancy of the population (over 15 years). The limited time horizon of the trial introduces a bias into the cost-effectiveness estimates of procedures, since the full costs are captured but only a portion of the benefits. Life-time projections of cost-effectiveness can remove this bias, but introduce uncertainties due to the model.
Medical therapy was quite cost-effective compared with prompt revascularization among patients in the PCI stratum, both in the within trial analysis () and the lifetime projection ($600 per life-year added). These results were robust in bootstrap replications and sensitivity analyses (), strongly suggesting that a strategy of medical therapy, with delayed revascularization only if clinically indicated, is more economically attractive than a strategy of prompt revascularization with PCI.
This result is consistent with the economic outcomes reported by other randomized trials of PCI and medical therapy in stable coronary disease. In the COURAGE trial, the cumulative costs among patients assigned to PCI were $11,000 higher over three years of follow-up than those of the patients assigned to medical therapy, and the lifetime cost of PCI patients was projected to be $9,500 higher. The cost-effectiveness ratio for PCI compared with medical therapy was $262,000 per life-year added in COURAGE (8
). The RITA-2 trial found that costs were significantly higher over three years follow-up (by 2685 pounds, or $4,385) among patients randomized to PCI compared with medical therapy (9
). Costs over one year follow-up were higher among PCI assigned than medically assigned patients in the MASS II trial (10
), and in the TIME trial patients assigned to invasive therapy (mostly PCI) had higher costs over one year of follow-up than patients assigned to medical therapy (11
). In decision models the cost-effectiveness of PCI depends primarily on the severity of angina, since highly symptomatic patients benefit from relief of angina (12
). Patients with severe symptoms despite medical therapy were excluded from BARI 2D, however. In patients with stable coronary disease and mild symptoms, PCI was not cost-effective, since it did not improve survival and led to much higher costs.
Patients in the CABG stratum had much higher costs after random assignment to prompt revascularization than to medical therapy, driven by the higher initial procedure costs. Patients in the CABG stratum were, however, significantly more likely to be free of major cardiovascular events after revascularization (77.6% at five years) than after medical therapy (69.5%). Over four years of follow-up, this reduction in clinical events did not increase life-expectancy sufficiently to be considered cost-effective by conventional benchmarks. Four years of follow-up is sufficient to capture all the costs of CABG, but only part of the benefit, however, and a lifetime projection is necessary to provide a fair perspective for the economic evaluation. These projections suggest that CABG may well be cost-effective compared with medical therapy for patients with diabetes ($47,000 per life-year added). This estimate was, however, variable in the bootstrap analysis and somewhat sensitive to model assumptions, and thus must be interpreted cautiously ().
BARI 2D represents, to our knowledge, the first trial-based comparison of the economic outcomes of CABG and medical therapy. The major trials comparing CABG with medical therapy were conducted before economic data were collected alongside clinical data in randomized trials. Decision models suggest that CABG is cost-effective relative to medical therapy among patients with either extensive anatomic disease or severe angina symptoms (12
). Patients with left main disease, extensive coronary disease, or severe angina requiring CABG were excluded from BARI 2D, however. Patients in the CABG stratum typically had more severe coronary disease, with three-vessel disease in 53% and reduced left-ventricular ejection fraction in 18% (15
). Our results are broadly consistent with the earlier decision models that demonstrated CABG to be cost-effective compared with medical therapy in higher risk patients (12
The insulin sensitization strategy in BARI 2D was more expensive than the insulin provision strategy, largely because of the higher cost of thiazolidinediones (). There was little evidence that the higher cost of insulin sensitizing drugs was offset by reductions in other cost categories () or by fewer clinical complications. The cost-effectiveness of the insulin sensitization strategy was therefore not favorable over the four-year time horizon of the trial (), but was more favorable in the lifetime projection (). This lifetime cost-effectiveness estimate was essentially a “toss-up”, however, since there were insignificant differences in long-term cost and survival between the insulin sensitization and insulin provision strategies (Appendix Figure
The glycemic control strategies tested in BARI 2D differ from the treatments evaluated in other trials, which generally assessed specific drugs or intensive versus conventional management approaches. Several prior studies suggest that intensive treatment to lower a HbA1c target may be cost-effective compared with more conventional management of diabetes (16
). In BARI 2D, however, the HbA1c target was the same in both the insulin provision and insulin sensitization strategies. There have been relatively few economic evaluations of the newer thiazolidinediones for patients with diabetes (22
). An economic model based on the PROactive trial (23
) suggested that use of pioglitazone among patients with type 2 diabetes and evidence of macrovascular disease may be cost-effective (24
). Over three years of follow-up, the patients assigned to pioglitazone had higher total costs (by 102 pounds, or $167) and greater survival, yielding a cost-effectiveness ratio of 5396 pounds ($8,811) per QALY, with a projected lifetime value of 4060 pounds ($6,631) per QALY. The PROactive trial design differed from that of BARI 2D in several ways, most notably in being a trial of a specific drug rather than a management strategy, and in achieving significantly different levels of glycemic control between the study groups.
This study has a number of limitations, the most important of which is that economic follow-up extended only to four years, less than the average of 5.3 years of clinical follow-up. Therefore, the within-trial cost-effectiveness evaluation did not capture the full effect of the assigned treatments on patient survival. While we projected survival and costs to assess lifetime cost-effectiveness, these estimates are subject to various uncertainties, and consequently must be interpreted cautiously. Furthermore, other clinical trials in diabetes have shown that survival differences may become evident only after ten years or more (25
). Longer follow-up of the BARI 2D patients, which is under consideration, would clarify the clinical effectiveness and cost-effectiveness of these strategies.
In conclusion, the strategy of prompt revascularization in patients with diabetes and coronary disease is significantly more costly than the strategy of medical therapy with delayed revascularization as needed. The medical strategy was cost-effective compared with the revascularization strategy in the stratum of patients with less severe coronary disease most suitable for PCI. Within the stratum of patients with more severe coronary disease identified as most suitable for CABG, the revascularization strategy may ultimately provide sufficient clinical benefits to be considered cost-effective.
The BARI 2D clinical trial randomized patients with diabetes and coronary disease to prompt coronary revascularization versus medical therapy, as well as to strategies of glycemia control based on use of either insulin sensitizers or drugs that increase insulin provision. Mortality over five years was not significantly different, but major cardiovascular events were reduced by revascularization in the CABG stratum. The present study shows that revascularization increases four-year cost significantly, by roughly $5,700 (PCI) to $20,300 (CABG), whereas insulin sensitization increases costs by $1,100. Medical therapy was highly cost-effective compared with prompt revascularization in the PCI stratum ($600/life-year added), suggesting that revascularization can be delayed until clinically indicated in patients with less extensive coronary disease. Revascularization may be cost-effective in patients with more extensive disease amenable to CABG, but this result was less certain with the limited follow-up available.