We really appreciate the clarifications offered by Alexandros
Briasoulis concerning his article, but in our opinion our claim about the
importance of including in the meta-analysis information only (or mostly)
from elderly patients remains well founded. In this regard, the Cochrane
Hypertension Group encourages to accept only studies if 70% or more of the
participants meet the definition, or individual patient data are
available, or data of relevant patients are provided separately allowing
specific inclusion of the population as defined (1). Moreover, the
inclusion of INVEST trial (2) in the ACCF/AHA 2011 (3) cannot be claimed
as a relevant argument to support proceeding in the same manner in the
meta-analysis, because of the inherent low level of evidence showed by
consensus. On the other hand, the INVEST trial has a very high risk of
bias. It is an open trial and no information on the sequence generation
nor the allocation concealment is provided.
We agree with the author in the conclusion showed by the secondary
analysis (4). But in fact this provides to us compelling evidence of the
importance of separating the information between young and older people.
Furthermore, it is not clear to us why these findings are said to be "in
accordance" with the results of the sensitivity analysis performed by the
author. According to the Discussion (1), the subgroup analysis of studies
with patients over 70 years showed that "the beneficial effects of
antihypertensive treatment remained significant in the first group of
studies (treatment versus placebo group)" but the meta-analysis did not
take into account blood pressure levels, thereby both papers seem to be
focused on very different issues. Also, we have not been able to read in
the last article cited (5) the assertion made on the J-curve association
in patients above or below age of 65. In fact, this study did not compare
different age subgroups any time but different blood pressure strata, and
the mean age values in each 10-mm Hg blood pressure stratum were very
similar (66-67 years).
In short, if elderly age begins at 65, we need to found our practices
on studies including real elderly people. Evidence based on the results of
studies with patients of a mean age close to 65 is not trustworthy.
(1) Gorricho J, Garjon J, Celaya MC, Muruzabal L, Montoya R, Lopez A,
Malon MDM, Saiz LC. Blood pressure targets for the treatment of patients
with hypertension and cardiovascular disease. Cochrane Database of
Systematic Reviews 2013, Issue 1. Art. No.: CD010315. DOI:
10.1002/14651858.CD010315.
(2) Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist
vs a non-calcium antagonist hypertension treatment strategy for patients
with coronary artery disease. The International Verapamil- Trandolapril
Study (INVEST): a randomized controlled trial. JAMA. 2003;290(21):2805-16.
(3) Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert consensus
document on hypertension in the elderly: a report of the American College
of Cardiology Foundation Task Force on Clinical Expert Consensus
Documents. Circulation. 2011;123:2434-2506.
(4) Denardo SJ, Gong Y, Nichols WW, et al. Blood pressure and outcomes in
very old hypertensive coronary artery disease patients: an international
verapamil ST-Trandolapril (INVEST) substudy. Am J Med. 18 2010;123:719-26.
(5) Messerli FH, Mancia G, Conti CR, et al. Dogma disputed: can
aggressively lowering blood pressure in hypertensive patients with
coronary artery disease be dangerous? Ann Intern Med. 2006;144:884-93.
Luis Carlos Saiz, Pharm D
Pharmacotherapy Research Coordinator
Navarre Health Service, Spain
Juan Erviti, Pharm D, PhD
Head of Unit, Drug Information
Navarre Health Service, Spain
Conflict of Interest:
None declared
We really appreciate the clarifications offered by Alexandros Briasoulis concerning his article, but in our opinion our claim about the importance of including in the meta-analysis information only (or mostly) from elderly patients remains well founded. In this regard, the Cochrane Hypertension Group encourages to accept only studies if 70% or more of the participants meet the definition, or individual patient data are available, or data of relevant patients are provided separately allowing specific inclusion of the population as defined (1). Moreover, the inclusion of INVEST trial (2) in the ACCF/AHA 2011 (3) cannot be claimed as a relevant argument to support proceeding in the same manner in the meta-analysis, because of the inherent low level of evidence showed by consensus. On the other hand, the INVEST trial has a very high risk of bias. It is an open trial and no information on the sequence generation nor the allocation concealment is provided.
We agree with the author in the conclusion showed by the secondary analysis (4). But in fact this provides to us compelling evidence of the importance of separating the information between young and older people. Furthermore, it is not clear to us why these findings are said to be "in accordance" with the results of the sensitivity analysis performed by the author. According to the Discussion (1), the subgroup analysis of studies with patients over 70 years showed that "the beneficial effects of antihypertensive treatment remained significant in the first group of studies (treatment versus placebo group)" but the meta-analysis did not take into account blood pressure levels, thereby both papers seem to be focused on very different issues. Also, we have not been able to read in the last article cited (5) the assertion made on the J-curve association in patients above or below age of 65. In fact, this study did not compare different age subgroups any time but different blood pressure strata, and the mean age values in each 10-mm Hg blood pressure stratum were very similar (66-67 years).
In short, if elderly age begins at 65, we need to found our practices on studies including real elderly people. Evidence based on the results of studies with patients of a mean age close to 65 is not trustworthy.
(1) Gorricho J, Garjon J, Celaya MC, Muruzabal L, Montoya R, Lopez A, Malon MDM, Saiz LC. Blood pressure targets for the treatment of patients with hypertension and cardiovascular disease. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD010315. DOI: 10.1002/14651858.CD010315. (2) Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil- Trandolapril Study (INVEST): a randomized controlled trial. JAMA. 2003;290(21):2805-16. (3) Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2011;123:2434-2506. (4) Denardo SJ, Gong Y, Nichols WW, et al. Blood pressure and outcomes in very old hypertensive coronary artery disease patients: an international verapamil ST-Trandolapril (INVEST) substudy. Am J Med. 18 2010;123:719-26. (5) Messerli FH, Mancia G, Conti CR, et al. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006;144:884-93.
Luis Carlos Saiz, Pharm D Pharmacotherapy Research Coordinator Navarre Health Service, Spain
Juan Erviti, Pharm D, PhD Head of Unit, Drug Information Navarre Health Service, Spain
Conflict of Interest:
None declared