Discussion
This study found that patients receiving care from 33 primary care clinics and who were initiated on 1 of 5 antihypertensive therapeutic classes as monotherapy had remarkably similar average reductions in blood pressure at follow-up (Table 5). These results are consistent with those found in a meta-analysis of 354 randomized, double-blind trials, which reported little difference in mean placebo-corrected reduction in blood pressure across the same 5 therapeutic classes. Our results extend this meta-analysis of efficacy studies done under strictly controlled conditions to the real world of effectiveness in daily practice.
Despite similar reductions in blood pressure across therapeutic classes, patients initiated on ACEIs and β-blockers had higher rates of JNC7 goal attainment than patients initiated on thiazide, even after adjusting for patient risk factors. The results of our study cannot be directly compared with those of the Treatment of Mild Hypertension Study, ALLHAT, or Materson et al; these evaluated efficacy by individual agents, whereas we evaluated effectiveness by therapeutic class. In addition, response to therapeutic classes has been shown to vary by race, and racial distributions are likely to be different between studies. Unfortunately, we did not have adequate racial data to adjust for this factor.
We also observed that primary care patients initiated on an FDC had considerably larger reductions in blood pressure and higher goal attainment rates at follow-up than patients initiated on monotherapy (Table 6). These results confirm those observed in short-term, randomized clinical efficacy studies and 2 recent observational studies, all of which showed that patients initiated on an FDC obtain better control of their blood pressure than patients initiated on monotherapy alone. However, both of the observational studies also demonstrated superior effectiveness in blood pressure control in patients initiated on an FEC when compared with patients on monotherapy, whereas there was little difference between these 2 treatment strategies observed in the present study. The lack of improved blood pressure control in patients initiated on an FEC could be due to the inclusion of combinations that have been identified by the American Society of Hypertension as being less effective (eg, ACEI and β-blocker, ARB and β-blocker, and ACEI and ARB). Another difference between the present study and the 2 observational studies is that the latter allowed for therapeutic classes to be added and dosages to be changed, while the present study did not. In addition, several studies have shown that patients taking an FDC have improved adherence over patients taking an FEC, which might further explain the differences seen in our study. Finally, the current study found that patients initiated on an FDC had larger reductions in blood pressure and superior rates of blood pressure control when compared with patients initiated on an FEC, which is similar to a report by Egan et al.
Effective treatment of high blood pressure is the key therapeutic strategy shown to reduce hypertension-related MACEs. However, hypertension frequently remains uncontrolled in the general population, and most patients require the combination of ≥2 drugs to reach recommended blood pressure goals. The American Society of Hypertension recently published a position paper recommending the routine use of combination therapy to achieve blood pressure targets and classifying combinations as preferred, acceptable, or less effective. The use of a combination of drugs from complementary classes at low doses has been shown to be more effective at lowering blood pressure than increasing the dose of a single agent. The use of low-dose combinations could potentially improve overall tolerability since most side effects of antihypertensive agents are dose-dependent and often drug-specific. While these benefits should apply regardless of whether they were initiated as an FDC or FEC, several studies have shown that patients taking an FDC have improved adherence over patients receiving an FEC since patient adherence is inversely related to the number of pills prescribed. The oft-stated disadvantage of FDCs has been their inability to independently titrate the doses of the component drugs along with higher cost because of the limited availability of generic FDCs. However, if goal attainment is better, the need for titration is lessened.
The strengths of this study include the use of patients from clinical practices, which allows for comparisons of initial hypertension treatment strategies and therapeutic classes outside of a research-intensive setting such as is seen in clinical trials; a geographically diverse sample of primary care clinics; a relatively large sample size; and the ability to adjust for differences in patient characteristics. However, there were several limitations to the study: (1) the observational nature of the study compared with a randomized clinical trial, which could lead to selection biases in the choice of treatments for the patients and residual confounding even after statistical adjustment for some important variables; (2) the inability to adjust for patient race/ethnicity, which had been shown to be associated with hypertension treatment; (3) the lack of prescription fulfillment data and pill counts or use of other techniques to monitor pills consumed by the patient; and (4) the lack of data on dose and dosing frequency.