Response to Reduction of Blood Pressure Levels Study Group
We appreciate Dr Mann’s1 question about whether the lack of home or ambulatory blood pressure (BP) measurements in the Consideration of Noninvasive Hemodynamic Monitoring to Target Reduction of Blood Pressure Levels (CONTROL) trial prevents the results from being considered definitive. In actuality, our study design minimized potential observer- and subject-expectation bias in the measurement of office BP. Therefore, the addition of either home or ambulatory BP would not have changed the study conclusion that impedance cardiography-guided therapy substantially improves BP control.
It is important to underscore that device-based, therapeutic management trials typically require an unblinded design and are not a placebo-controlled arm. In our design, the use of a standard care as the comparator group was the most appropriate approach to evaluate differences. Inherently, these types of trials require an unblinded physician and subject who are engaged in the strategy under evaluation. Thus, the design of our study minimized potential observer- and subject-expectation bias.
Our study did address the potential for observer-expectation bias in the recording of office BP through the use of an automatic oscillometric BP cuff, performed and recorded under strict protocol by a technician who was not involved in patient management. If we had used patient-administered, home-BP measurements, it may have introduced more methodologic variation and patient bias in recording the values, as has been shown in other studies.2
Although ambulatory BP measurements have been used in trials to attempt to minimize subject-expectation bias, studies have demonstrated a reduction in both office and ambulatory BP measurements with placebo-based treatment.3,4 That may be because any placebo effect is only one part of the total therapeutic effect and is accompanied by multiple factors other than subject expectancy, such as the physician–patient interaction. In the CONTROL Trial, some degree of subject expectancy existed in both arms, because all of the patients were told that their BPs were not under control, and all expected to receive aggressive treatment. If treatments were similar in both arms but office BP readings were different, then subject-expectation bias could have been a major factor. However, the greater office BP reductions in the ICG-hemodynamic arm were accompanied by significant differences in treatment that were mechanistically consistent with the recommended ICG-treatment strategy and trial hypothesis: (1) greater use of vasodilating agents when systemic vascular resistance was high; (2) less β-blocker use when cardiac output was normal or low; and (3) less trial-and-error through fewer dose increases and decreases. Therefore, it is highly unlikely that treatment differences would have resulted in changes in office but not ambulatory BP.
We acknowledge that when both ambulatory and office BP have been measured in trials, the differences between antihypertensive treatments on ambulatory BP are 25% to 33% less than office BP.5 Applying these ratios to our study, the 8/7-mm Hg incremental reduction from baseline achieved in the ICG-hemodynamic arm would equate to a 5.4- to 6.0-mm Hg systolic and 4.7- to 5.3-mm Hg diastolic BP advantage. This advantage in BP reduction is still impressive and much greater than the 1- to 2-mm Hg threshold typically used to judge one antihypertensive agent favorably versus another.6
For the aforementioned reasons, the addition of home or ambulatory BP would have had no influence on the findings and interpretation given to the CONTROL Trial results. When this trial is considered with the previous randomized trial in resistant hypertension,7 the data clearly demonstrated that use of ICG measurements definitively improves BP control.
C.M.F. and R.D.S. have received honorarium from Cardio-Dynamics for consultation and speaker fees.
Mann SJ. Reduction of blood pressure levels study group. Hypertension. 2006; 48: e104.
Mengden T, Hernandez Medina RM, Beltran B, Alvarez E, Kraft K, Vetter H. Reliability of reporting self–measured blood pressure values by hypertensive patients. Am J Hypertens. 1998; 11: 1413–1417.
Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension. 2002; 39: 982–988.