Additional information regarding the SEVITENSION study.

Dear Dr. Menown,

I am pleased to report that we have received considerable interest since the publication of our article (Ruilope L, Schaefer A. The fixed-dose combination of olmesartan/amlodipine was superior in central aortic blood pressure reduction compared with perindopril/amlodipine: a randomized, double-blind trial in patients with hypertension. Adv Ther. 2013;30:1086–99 [1]) last December. The results confirmed the effects of combined renin angiotensin system and calcium channel blockade on lowering central blood pressure. Furthermore, it extended these findings by showing that the angiotensin II receptor blocker olmesartan medoxomil could produce similar changes in central blood pressure when combined with a calcium channel blocker.

One enquiry concerned the levels of baseline blood pressure in the treatment groups described in the report. We are happy to provide these baseline values here, but feel that it is advisable to first remind readers of the context in which these data should be viewed. The use of a 4-week run-in period before the start of double-blind treatment meant that all patients had been treated with amlodipine for at least 4 weeks (Table 1 footnotes). Some patients would have received amlodipine 5 mg for the first 2 weeks of the run-in period and then been uptitrated to amlodipine 10 mg for the final 2 weeks. Furthermore, some patients had also received other antihypertensive agents for up to 2 weeks before the start of double-blind treatment and some had received amlodipine 10 mg for more than 2 weeks. Amlodipine is an effective antihypertensive agent and even though patients entered double-blind treatment only if their blood pressure control was inadequate, the treatments used prior to double-blind treatment would have already produced significant reductions in blood pressure. This should be remembered when looking at the baseline data (Table 1). Also, as specified in the study protocol, the per protocol set was used to assess changes in the primary variable (central systolic blood pressure) and the full analysis set was used for analysis of all other parameters.

Table 1

Baseline hemodynamic characteristics of patients who entered double-blind treatment

Characteristics	OLM/AML (40/10 mg)	PER/AML (8/10 mg)	Total
Per protocol set	n = 198	n = 192	n = 390
Central SBP, mmHg	135.3 (11.57)	135.2 (10.89)	135.3 (11.22)
Full analysis set	n = 221	n = 221	n = 442
Seated SBP, mmHg	148.5 (10.30)	148.9 (11.93)	148.7 (11.13)
24-h ambulatory SBP, mmHg	134.8 (11.62)	133.3 (11.28)	134.0 (11.46)
Daytime ambulatory SBP, mmHg	138.3 (12.10)	137.1 (11.58)	137.7 (11.84)
Night-time ambulatory SBP, mmHg	126.9 (12.72)	125.0 (13.02)	125.9 (12.89)
Central DBP, mmHg	86.8 (9.30)	87.3 (9.68)	87.1 (9.48)
Seated DBP, mmHg	85.8 (8.92)	86.1 (9.43)	86.0 (9.17)
24-h ambulatory DBP, mmHg	79.2 (8.76)	79.2 (8.36)	79.2 (8.55)
Daytime ambulatory DBP, mmHg	82.0 (9.31)	82.1 (8.44)	82.0 (8.88)
Night-time ambulatory DBP, mmHg	73.1 (8.76)	73.1 (9.52)	73.1 (9.14)

Values are mean (standard deviation)

Before starting double-blind treatment patients entered a 4-week run in, unless they had been receiving amlodipine 10 mg as monotherapy before the study (in which case they entered double-blind treatment directly). Patients who had been receiving drug treatment before the study continued with their former medication (except for calcium channel blockers) during the first 2 weeks of the run in and also received amlodipine 5 mg once daily. During the final 2 weeks of the run in, all former medications were withdrawn and patients received amlodipine 10 mg as their only treatment. Patients entered double-blind treatment if their seated systolic blood pressure/diastolic blood pressure was ≥140/90 mmHg (≥130/80 mmHg for diabetes or CKD). For a description of the per protocol and full analysis sets, please see Ruilope and Schaefer [1]

AML amlodipine, DBP diastolic blood pressure, OLM olmesartan, PER perindopril, SBP systolic blood pressure

Yours sincerely,

Professor Luis Ruilope