Between January 2000 and July 2002, 147 physicians were recruited and randomized to the control and intervention groups (). Fifty-four physicians (24 in the control arm and 30 in the intervention arm) withdrew before recruiting any patients. Fourteen physicians (11 in the control arm and 3 in the intervention arm) withdrew study consent prior to their 40 patients starting follow-up. Twelve patients (5 in the control arm and 7 in the intervention arm) were excluded because of protocol violations. Eight patients (3 in the control arm and 5 in the intervention arm) did not have follow-up data. Therefore, 79 physicians (39 in the control arm and 40 in the intervention arm) and 875 of their patients (457 in the control arm and 418 in the intervention arm) were available for complete analysis. Among those, MEMS data were not available for 78 patients (8.9%) for different reasons (14 devices were lost, 2 patients never used the MEMS, 4 MEMS were defective, 58 MEMS were not returned by the patient or the investigator). There were no statistically significant differences in the distribution of those patients between the intervention and the control group.
Flow of patients and physicians during recruitment and the first 6 months of follow-up.*Patients also included in (Baseline characteristics).
and show the characteristics of physicians and patients, respectively, in the control and intervention groups. All characteristics were similar with the exception that baseline DBP, heart rate, and self-reported medication nonadherence were significantly higher among patients in the intervention group when compared with control group patients.
Distribution of patient related characteristics in control and intervention groups. Numbers are mean ± SD[N], and Ns (%).
The mean duration of patient follow-up was 39 months, and 67% of the patients had at least 36 months of follow-up. The ICCs for the outcomes of interest were as follows: 0.197 for SBP, 0.194 for DBP, 0.107 for adherence, and 0.063 for combined cardiovascular events. shows the study results for BP and adherence outcomes in the first 6 months of follow-up. At six months, intervention patients had significantly lower mean SBP (148.9 mmHg vs. 151.1 mmHg; P=0.008) and lower mean DBP (81.9 mmHg vs. 83.0 mmHg; P=0.013) when compared with control patients. Moreover, intervention patients were less likely to have an uncontrolled SBP (i.e., ≥ 140mmHg) when compared with control patients (OR 0.62; 95% CI 0.50, 0.78). On the other hand, intervention patients were not less likely to have an uncontrolled DBP (i.e., ≥ 90mmHg) when compared with control patients (OR 0.94; 95% CI 0.73, 1.20). Differences around 2mm of Hg in SBP between groups persisted over the 5-years of follow-up, whereas differences in DBP between groups were < 1mmHg after 18 months of follow-up (). Only a few of the SBP differences after the 6-month visit were statistically significant.
Comparison of blood pressure and adherence outcomes between the control and the intervention group during the first 6 months of follow-up.
Systolic and diastolic blood pressure differences between the intervention and the control group during the 60 months follow-up. Asterisks mark the visits in which differences in BP favoring the intervention group were of 1.5 mm of Hg or more.
Patients in the intervention group also appeared to be more adherent over the six months of the intervention, as they took their correct dose on a greater proportion of days when compared with patients in the control group (92.2% vs. 89.0%, respectively; P=0.002) and were more likely to be at least 80% adherent (OR 1.91; 95% CI 1.19, 3.05) (). For the other adherence measures, intervention patients were also more likely to achieve a value ≥ 80% adherence over the six-month period. Expanded , , and and additional methods descriptions are available on-line.
During the study it was discovered that the MEMS chips of 45 containers malfunctioned at least once in the study, resulting in inflated measurements of between 4–8 uses per day. The malfunctioning MEMS containers were replaced by the manufacturer who also developed an algorithm to identify and delete invalid readings. Through this algorithm we estimated that approximately 5% of all readings on the defective devices were invalid. As a sensitivity analysis, we repeated the analysis excluding the 45 patients who had defective devices and the results did not change (data not shown).
After five years of follow-up, 153 patients had at least one of the composite cardiovascular events - 67 (16%) in the intervention group and 86 (19%) in the control group (). Although intervention patients had fewer events when compared with control patients, after adjusting for DBP, age, gender, self-reported measures of adherence, and cardiovascular risk profile, this difference was not statistically significant (hazard ratio 0.97; 95% CI 0.67,1.39).
Figure 3 Kaplan-Meier survival curve for cardiovascular end-points comparing the intervention and the control groups (log-rank test, P = 0.351). The plot shows unadjusted results. Survival results after adjusting, using a multivariable survival Cox model accounting (more ...)