The majority of cohorts achieved some benefit from aspirin. However, in all the cohorts, regardless of age and gender, we found that the decision to use aspirin as a chemoprophylactic agent depended on the risk profile ( and ). The model suggested that aspirin not be taken in the cohorts with the lowest-risk profile (loss of 1.83 quality-adjusted days in 10 years of follow-up) and favored taking aspirin in the cohorts with higher-risk profiles (gain of 3.3 to 11.3 quality-adjusted life days in 10 years of follow-up). Regarding aspirin's effect in crude life expectancy, all cohorts benefited from receiving aspirin with a net benefit ranging from 0.73 to 8.04 days (see and ). In general, the benefit of aspirin was greater as the number of risk factors increased. The presence of LVH had different effects among the different cohorts; it increased the benefit of aspirin in 55-year-old women but diminished the benefit of aspirin in all other cohorts. This seemingly contradictory effect could be explained by LVH's significant effect on stroke incidence and relatively low incidence of stroke in 55-year-old women.
Difference in 10-Year Survival in 55-Year-Old Cohorts*
Difference in 10-Year Survival in 65-Year-Old Cohorts*
We tested the stability of the model performing one-way sensitivity analysis on the probabilities that are less certain in the literature (annual ulcer incidence and major bleeds) ( The model was robust for most of the ranges of aspirin's relative effects on probabilities (nonfatal MI, ulcer, and major bleeding). The model was also robust for the ranges of most utilities (nonfatal MI, disabling and nondisabling stroke, ulcer, and major bleeding). In the cohorts of 65-year-old men and women (data not shown for women), the optimal strategy to take aspirin was also sensitive to aspirin's effect on stroke incidence.
Threshold Values for Comparison Between Treatment Strategies for Cohorts of 65-Year-Old Men and 55-Year-Old Women*
Two variables were extremely significant in one-way sensitivity analysis: the utility of taking aspirin and aspirin's relative effect on cardiovascular-related mortality. All the cohorts tested were sensitive to the utility of taking aspirin and to aspirin's effect on cardiovascular mortality. To show the pattern of variables that were sensitive in the different cohorts, demonstrates a threshold analysis of key variables in 65-year-old male cohorts and in 55-year-old female cohorts.
The interpretation of the results in is dependent on the optimal decision recommended by the model, the type of variable under examination by the one-way sensitivity analysis (i.e., probability of event, relative risk of aspirin's effects, or utility of adverse outcome), and whether or not a threshold exists.
For the rows not in boldface type, the baseline analysis recommended taking aspirin. In these scenarios, if a threshold value for the probability of an event or the relative risk of aspirin's effects does not exist, then the optimal decision to take aspirin is robust to variation in the parameter under examination. Alternatively, if a threshold value for the probability of an event or the relative risk of aspirin's effects does exist, then for any value greater than the threshold, not taking aspirin would become the optimal decision.
Similar reasoning can be made for utility thresholds when the baseline analysis recommended taking aspirin. However, for utilities there are two different effects—one for the burden (disutility) of taking aspirin, and the other for the burden of MI. If a threshold exists for the utility of taking aspirin, then a decrease in the utility of that health state to the threshold or lower will change the optimal decision to not take aspirin. If the utility for non-fatal MI becomes greater than the threshold for that variable, then again the recommendation changes to not take aspirin.
For example, in the cohort of the next-to-highest-risk 65-year-old men (sixth row of top part of ), the baseline analysis indicated that aspirin was the optimal strategy. demonstrates the threshold analysis. For utility values smaller than 0.9966, rather than the base case value of 0.999, the no-aspirin strategy would be recommended. In that same cohort, if the relative risk of stroke while taking aspirin were greater than 1.3075, then the no-aspirin strategy would be recommended (compare with base case, for which relative risk of stroke equals 1.17).
Threshold analysis: 65-year-old men with five risk factors. Shaded region indicates that no aspirin is optimal strategy.
The logic is reversed when a cohort's optimal strategy in the baseline analysis was to not take aspirin, designated by the boldface rows in . Again, the interpretation of the threshold is dependent on the variable that is examined in the one-way sensitivity analysis. For the threshold for the utility of the health state of taking aspirin, the optimal decision would change from not taking aspirin to taking aspirin for any value higher than the threshold. No other probability variable has a threshold for the cohorts originally better off with the no-aspirin strategy. Thus, no reasonable change in these probabilities would change the optimal recommendations for these cohorts. With regard to the cohorts for which the initial choice was no aspirin: if a threshold exists for the effects of aspirin, relative risk variables of effect, a value smaller than the threshold would change the optimal choice from the no-aspirin strategy to the aspirin strategy.
The above reasoning is demonstrated in the threshold analysis for the cohort of lowest-risk 55-year-old women (). In this cohort the baseline analysis showed that no aspirin was the optimal strategy. If the utility of the health state of taking aspirin were 0.9997 or higher, then taking aspirin would be recommended. Similarly, the aspirin strategy would be favored if aspirin's relative risk on fatal vascular events were less than 0.8378 (compare with baseline value for aspirin's relative effect on cardiovascular mortality equal to 0.98).
Threshold analysis: 55-year-old women with no risk factors. Shaded region indicates that no aspirin is optimal strategy.
For the purposes of clinical applicability, we show in and all the possible cohorts and aspirin's potential benefit in each of them. Although in the great majority of possible cohorts the aspirin strategy was better than the no-aspirin strategy, these tables demonstrate the cohorts that most benefit from taking aspirin, as indicated by a boldface A. In these cohorts, the benefit of taking aspirin was equal to or greater than 3.5 quality-adjusted life days, which we considered a clinically relevant difference, especially considering the significant impact that the administration of aspirin could have at the population level.
Aspirin Primary Prevention Table of Risk Factors for Men*
Table Aspirin Primary Prevention Table of Risk Factors for Women*