CASE VARIATION—50-YEAR-OLD WHITE MAN
Better reductions than for 65 year old
For the 50-year-old man ( TABLE 4 ), risk for CVA was substantially lower and the risk for foot ulceration was somewhat higher than for the base case (ARs 7.1% and 8.6% vs 14.4% and 5.2%, respectively). Risk reductions for MI associated with aspirin and moderate exercise were greater at age 50 than at age 65 (ARRs=9.6% and 10.1% vs 6.8% and 2.7%, respectively). This was also true, but to a lesser extent, for tight control of BP and LDL (ARRs=7.1% and 4.9% vs 5.0% and 3.5%, respectively). Weight loss had only a minimal effect on risk of MI, CVA, and foot ulceration. Using an ACE inhibitor did not affect risk of any of the outcomes.
TABLE 4
Absolute risk reduction predicted by Archimedes risk engine
50-year-old white male, sedentary, nonsmoker with a 5-year history of diabetes mellitus; BMI 27 kg/m2; BP 140/90 mm Hg; HbA1c 10%; L DL 120 mg/dL; HDL 45 mg/dL
| MI | CVA | ESRD | BLINDNESS | FOOT ULCERATION | FOOT AMPUTATION | |
|---|---|---|---|---|---|---|
| 10-year AR before interventions | 22.2 | 7.1% | 0% | 0% | 8.6% | 0% |
| INTERVENTIONS* | RISK (ARR) | |||||
| Aspirin, 81 mg/d | 12.6% (9.6%) | 6.9% (0.2%) | 0% (0%) | 0% (0%) | 8.5% (0.1%) | 0% (0%) |
| Moderate aerobic exercise | 12.1% (10.1%) | 3.7% (3.4%) | 0% (0%) | 0.1% (-0.1%) | 8.8% (-0.2%) | 0% (0%) |
| Reduce BMI to 25 kg/m2 | 22.0% (0.2%) | 7.0% (0.1%) | 0% (0%) | 0% (0%) | 8.5% (0.1%) | 0% (0%) |
| Reduce HbA1c to 7.0% | 17.2% (5.0%) | 5.5% (1.6%) | 0% (0%) | 0% (0%) | 3.4% (5.2%) | 0% (0%) |
| Reduce HbA1c to 6.5% | 16.1% (6.1%) | 5.2% (1.9%) | 0% (0%) | 0% (0%) | 3.4% (5.2%) | 0% (0%) |
| Reduce SBP to 130 mm Hg | 17.8% (4.4%) | 5.9% (1.2%) | 0% (0%) | 0% (0%) | 8.6% (0%) | 0% (0%) |
| Reduce SBP to 120 mm Hg | 15.1% (7.1%) | 5.2% (1.9%) | 0% (0%) | 0% (0%) | 8.6% (0%) | 0% (0%) |
| Reduce LDL to 100 mg/dL | 20.1% (2.1%) | 7.1% (0%) | 0% (0%) | 0% (0%) | 8.5% (0.1%) | 0% (0%) |
| Reduce LDL to 70 mg/dL | 17.3% (4.9%) | 5.2% (1.9%) | 0% (0%) | 0% (0%) | 8.3% (0.3%) | 0% (0%) |
| β-Blocker | 19.2% (3.0%) | 6.5% (0.6%) | 0% (0%) | 0% (0%) | 8.6% (0%) | 0% (0%) |
| All of the above | 2.0% (20.2%) | 1.3% (5.8%) | 0% (0%) | 0% (0%) | 3.1% (5.5%) | 0% (0%) |
| AR, absolute risk; ARR, absolute risk reduction; BMI, body mass index; BP, blood pressure; CVA, cerebrovascular accident; ESRD, end-stage renal disease; HbA1c, glycosylated hemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MI, myocardial infarction; SBP, systolic blood pressure. | ||||||
| *Use of an ACE inhibitor had no effect on any outcome | ||||||
Based on projections derived from Archimedes, patients with diabetes who are older than 50 years are at far less risk for microvascular complications than for macrovascular complications. Older patients are 20 times more likely to experience heart attack and stroke than ESRD, blindness, or amputation.
It’s important to keep in mind here that comparisons between various interventions in these test cases depend entirely on the initial values of the risk factors. So, for example, we are comparing a 3% reduction in HbA1c with a 20 mg/dL reduction in LDL and a 20 mm Hg reduction in BP.
Our estimates differ substantially from those reported by Eastman and colleagues, who used Monte Carlo techniques to model outcomes for a representative sample of patients with type 2 diabetes using data from several epidemiologic studies.15,16 They projected lifetime risks of 17% for ESRD and amputation and a lifetime risk of 39% for cardiovascular events. These differences can probably be accounted for by the inclusion of a number of younger patients in the Eastman sample, a longer projected time frame (lifetime vs 10 years), and a different modeling technique. The Archimedes projections of these complications are actually higher than those reported in a recently published longitudinal study based on Medicare claims.17
Benefit of aspirin and exercise together. Of the available interventions to reduce risk of MI and CVA, the least expensive ones, aspirin and moderate exercise, appear to be at least as effective as the others. In fact, even in the base case, in which exercise was somewhat less effective than in the variations, the combination of aspirin and exercise reduced the risk of MI by 8.9% (59% of the maximum possible ARR) and reduced the risk of CVA by 7.8% (70% of the maximum ARR).
Rigorous validation of Archimedes
In 2003, Archimedes underwent a series of 74 validation exercises involving 18 randomized controlled trials31,32 chosen on the basis of quality of design, importance of results, and a wide range of patient populations.
Ten of the trials explicitly included people with diabetes; 8 others were chosen to test the model’s validity for representing coronary artery disease, an important complication of type 2 diabetes.
Ten of the trials had not been used to build the Archimedes model and, as such, served as external validation of the model. The other 8 trials, which had been used to help build the model, provided internal validation.
The correlation between results predicted by Archimedes and the actual results of the clinical trials for all 74 exercises was nearly perfect (r=0.99). With 71 of the 74 exercises, there were no statistically significant differences between the results calculated by the model and the results observed in the trials.31