Randomized controlled trial evidence from the ALLHAT trial and the subsequent revision of clinical guidelines for the treatment of hypertension were temporally associated with a moderate increase in diuretic use and a moderate decrease in ACE inhibitor use in this multi-ethnic cohort study. These time trends appeared to be stronger in male participants.
The MESA study is prospective study using a population-based cohort with new users both before and after this time period making it ideal to assess the effects of this new information on patterns of medication use. The MESA study also uses a well-validated inventory approach to the assessment of medication use among the study participants [12
]. Finally, as the MESA cohort is free of cardiovascular disease at baseline, the use of this cohort enables us to assess the effect of these revised guidelines in a relatively healthy population.
A limitation of the MESA study is the potential under-reporting of medication use. This could occur due to a failure to include a medication in the supply brought to a study visit. This effect is unlikely to be differential by drug class. Another limitation of this investigation is that drug exposure was sampled at visits that were approximately 18 months apart and information about treatments between visits is not available.
The findings of this study are consistent with the findings of Stafford et al. who found a short term boost in diuretic prescriptions following the release of the ALLHAT recommendations [17
] and Muntner et al. who found a more sustained increase in diuretic prescriptions post-ALLHAT [18
]. The results of this study are also consistent with other cohort studies, such as the Cardiovascular Health Study [19
] in that they suggest that changes in evidence-based prescribing guidelines can have some impact on physician prescribing behavior.
The reason for the different rate of diuretic prescribing for male participants versus female participants is unknown. The effect of gender could be attributed to differences in how physicians treat male and female patients, differences in comorbid conditions, differences in the indications for starting these drugs, patient preferences, differential treatment for conditions other than hypertension or some other unknown factor. These same factors could also explain why not all patients are started on low-dose diuretics after the release of the guidelines.
The continued use of ACE inhibitors as first line anti-hypertension therapy might be due to the other potential beneficial effects of these drugs that were reported from observational studies during this time period. These drugs were reported to be associated with lower rates of a variety of conditions including renal disease [21
], chronic obstructive pulmonary disease [22
], headaches [23
] and dementia [24
]. These possible secondary benefits of ACE inhibitor use might explain the continued use of this drug class among new users despite the changes in recommendations for first line anti-hypertensive therapy.
Calcium channel blockers and alpha-blockers are no longer recommended as first line agents [9
]. Consistent with these guidelines, both agents were being prescribed less frequently than diuretics among new users. It is also possible that many of the alpha-blocker prescriptions could be intended for the treatment of benign prostatic hyperplasia [25
] instead of hypertension. While the use of these agents did not decrease over the course of this study, the levels of use among new users were already low compared to other anti-hypertensive agents. Conversely, the frequent use of beta blockers as first-line anti-hypertensive therapy was consistent with previous treatment guidelines [2
This study suggests that the release of important RCT evidence and the consequent revision of clinical guidelines may influence the selection of first-line therapy for hypertension in a population-based, multi-ethnic cohort. Based on the results of this study, we suggest that it is important to ensure that the post-ALLHAT shift to increased first line treatment with low dose diuretics for male patients should be maintained.
- Diuretic use increased in male new users of antihypertensive medications (to the levels seen in female new users) while ACE inhibitor use dropped after the release of key randomized controlled trial evidence supporting low dose diuretic use
- This increase in diuretic use among male new users persisted for at least one follow-up exam in participants in the Multi Ethnic Study of Atherosclerosis