The low rate of antihypertensive medication adherence in this statewide Medicaid population (39.4%) replicates the findings of other researchers in other insured populations.34,35
This study demonstrates that low antihypertensive medication adherence is a potent cardiovascular risk factor for community-dwelling hypertensive patients and that increasing adherence by just one pill per week for a once-a-day regimen (i.e., increasing MRA by 15%) can result in a 7% reduction in hazard of death or a number needed to treat (NNT) of 344 to prevent one death in 2.7 years. This compares very favorably with the NNT estimated at greater than 500 for cholesterol-lowering therapy to prevent one death in 5 years for patients with two or more risk factors such as hypertension.15,36
This study demonstrates that medication adherence, a factor very amenable to change, is among the most important cardiovascular risk factors for hypertensive patients. We found a 0.5% increase in deaths over 5 years attributable to non-adherence (MRA
80%). Given that there are approximately 68 million US adults with hypertension37
and approximately 60% are non-adherent by this standard, these results suggest than approximately 200,000 lives could be saved over the next 5 years by increasing adherence levels for all hypertensive patients to ≥80%. These estimates of the lives saved by improved adherence and control of hypertension are consistent with the estimates of other authors.37,38
It is likely that a similar number of strokes could be prevented through increases in adherence, but our study had insufficient stroke events and was underpowered to show significant impact on stroke in the survival analysis due in part to the stringent requirements for stroke diagnosis.
Of particular interest to generalist physicians is the finding that increased ambulatory care was associated with decreased mortality risk. This study, unlike previous studies of cohorts of patients with chronic disease,12–14
found that ambulatory visits were protective for death once we controlled for the impact of comorbidity. The most notable of previous studies to assess the impact of ambulatory care showed that recently hospitalized veterans with diabetes, chronic obstructive pulmonary disease, or congestive heart failure randomized to an intensive primary care intervention actually experienced higher readmission rates.12
The results of our community-based observational study are reassuring and are consistent with the a priori expectation of primary care physicians that their outpatient efforts to control hypertension pay off. Although the effect size for ambulatory visits was small, this study is to our knowledge the first to give clear evidence that ambulatory visits in community settings are beneficial for hypertensive patients. This finding is striking since ambulatory visits are subject to confounding by indication; sicker people go to the doctor more. By using meticulous methods to control for the effects of comorbidity, the current study was able to unmask the impact of ambulatory care.
The effect of ambulatory care is likely mediated by increasing opportunities for measurement and improvement of hypertension control. The finding that baseline emergency care exposure was protective for death suggests that emergency visits may also provide important opportunities to identify and treat patients with uncontrolled hypertension. Further research is needed to determine the optimal number and types of visits needed to maintain blood pressure control and prevent adverse events, the primary mechanisms through which ambulatory visits improve outcomes, and the most effective methods for improving adherence and control of hypertension in ambulatory settings.13
This study also demonstrated that exposures to most major classes of antihypertensives were protective for mortality independent of adherence levels. This is consistent with clinical trials and meta-analyses of hypertension outcome trials demonstrating similar mortality benefits for these major classes.39
Only baseline CCB exposure was associated with increased risk of stroke, possibly because patients started on CCBs generally have more severe hypertension. Combination antihypertensive medication exposure was not independently associated with decreased risk of stroke or death.
The protective effects of thiazide-type diuretic exposure were most notable. Recent thiazide exposure decreased risk of stroke by 11%, the only medication exposure other than aspirin that was associated with decreased risk of stroke. Both baseline and recent thiazide use decreased risk of death. These impacts are particularly robust given that we controlled for exposure to other classes of medication, adherence, number of medications taken, and other well-validated measures of comorbidity. Our study is consistent with previous major randomized clinical trials and meta-analyses of antihypertensive therapy in showing that the lowest cost antihypertensive medications (thiazide-type diuretics) are lifesaving and prevent stroke.15,40,41
The limitations of this study are inherent in the use of administrative data. Lack of access to clinical data prevented our measuring potential confounding variables such as severity of hypertension. However, the study has high external validity in that it fairly represents the health services exposures and clinical outcomes for a large population of patients with a very common condition. Although we had limited ability to measure and adjust for differences in comorbidity, we were able to employ well-validated methods for comorbidity adjustment of administrative data.17
The current study may have underestimated the effect of non-adherence by using a measure of adherence (i.e., MRA) that combines those who are adherent and those who receive an oversupply of antihypertensive medication from their pharmacy. Some recent studies indicate that oversupply may also be associated with non-adherence.42,43
Including the type of medication exposure variables in the same multivariate model with MRA may have further diluted the effect of adherence on stroke and death because of collinearity between these independent variables. Therefore, the effect of adherence demonstrated in this study likely represents a lower estimate than the true effect of adherence on stroke and death.
Healthy user bias could account for the unexpected protective effects of obesity for stroke and death, and hypercholesterolemia and history of myocardial infarction (MI) for death. Because coding forms have limited space for diagnoses, healthier patients are more likely to have stable chronic diagnoses listed as a code on the claim. So, the study’s findings regarding obesity, hypercholesterolemia, and history of MI are probably explained by an administrative coding phenomenon. The study’s generalizability is also potentially limited by its assessment of practice patterns 9 to 15 years ago. Although studies suggest that treatment of hypertension has become more aggressive since the late 1990s, there have been no major changes in treatment guidelines or medication copayments for Medicaid patients since that period. These results cannot be generalized to older Medicare patients since they were not included in the study.
This study suggests that MRA can be used by primary care physicians at the point of care to recognize, track, and improve adherence and save lives. This research supports making MRA information readily available through electronic medical records to providers to help them support patient adherence. The study also supports clinical trial evidence and US guideline recommendations supporting frequent use of thiazide-type diuretics in the management of hypertension. In summary, adherence serves as a key mediator of risk of premature stroke and death that is amenable to action, and the best place for action is in the ambulatory setting.