Blood pressure targets for hypertension in people with diabetes mellitus

  • Review
  • Intervention

Authors

  • Jose Agustin Arguedas,

    Corresponding author
    1. Universidad de Costa Rica, Depto de Farmacologia Clinica, Facultad de Medicina, San Pedro de Montes de Oca, Costa Rica
    • Jose Agustin Arguedas, Depto de Farmacologia Clinica, Facultad de Medicina, Universidad de Costa Rica, San Pedro de Montes de Oca, Costa Rica. drarguedas@ampmd.com.

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  • Viriam Leiva,

    1. University of Costa Rica, Escuela de Enfermeria, Facultad de Medicina, San Jose, Costa Rica
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  • James M Wright

    1. University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada
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Abstract

Background

When treating elevated blood pressure (BP), doctors often want to know what blood pressure target they should try to achieve. The standard blood pressure target in clinical practice for some time has been less than 140 - 160/90 - 100 mmHg for the general population of people with elevated blood pressure. Several clinical guidelines published in recent years have recommended lower targets (less than 130/80 mmHg) for people with diabetes mellitus. It is not known whether attempting to achieve targets lower than the standard target reduces mortality and morbidity in those with elevated blood pressure and diabetes.

Objectives

To determine if 'lower' BP targets (any target less than 130/85 mmHg) are associated with reduction in mortality and morbidity compared with 'standard' BP targets (less than 140 - 160/90 - 100 mmHg) in people with diabetes.

Search methods

We searched the Database of Abstracts of Reviews of Effectiveness (DARE) and the Cochrane Database of Systematic Reviews for related reviews. We conducted electronic searches of the Hypertension Group Specialised Register (January 1946 - October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE (January 1946 - October 2013), EMBASE (January 1974 - October 2013) and ClinicalTrials.gov. The most recent search was performed on October 4, 2013.

Other search sources were the International Clinical Trials Registry Platform (WHO ICTRP), and reference lists of all papers and relevant reviews.

Selection criteria

Randomized controlled trials comparing people with diabetes randomized to lower or to standard BP targets as previously defined, and providing data on any of the primary outcomes below.

Data collection and analysis

Two review authors independently assessed and established the included trials and data entry. Primary outcomes were total mortality; total serious adverse events; myocardial infarction, stroke, congestive heart failure and end-stage renal disease. Secondary outcomes were achieved mean systolic and diastolic BP, and withdrawals due to adverse effects.

Main results

We found five randomized trials, recruiting a total of 7314 participants and with a mean follow-up of 4.5 years. Only one trial (ACCORD) compared outcomes associated with 'lower' (< 120 mmHg) or 'standard' (< 140 mmHg) systolic blood pressure targets in 4734 participants. Despite achieving a significantly lower BP (119.3/64.4 mmHg vs 133.5/70.5 mmHg, P < 0.0001), and using more antihypertensive medications, the only significant benefit in the group assigned to 'lower' systolic blood pressure (SBP) was a reduction in the incidence of stroke: risk ratio (RR) 0.58, 95% confidence interval (CI) 0.39 to 0.88, P = 0.009, absolute risk reduction 1.1%. The effect of SBP targets on mortality was compatible with both a reduction and increase in risk: RR 1.05 CI 0.84 to 1.30, low quality evidence. Trying to achieve the 'lower' SBP target was associated with a significant increase in the number of other serious adverse events: RR 2.58, 95% CI 1.70 to 3.91, P < 0.00001, absolute risk increase 2.0%.

Four trials (ABCD-H, ABCD-N, ABCD-2V, and a subgroup of HOT) specifically compared clinical outcomes associated with 'lower' versus 'standard' targets for diastolic blood pressure (DBP) in people with diabetes. The total number of participants included in the DBP target analysis was 2580. Participants assigned to 'lower' DBP had a significantly lower achieved BP: 128/76 mmHg vs 135/83 mmHg, P < 0.0001. There was a trend towards reduction in total mortality in the group assigned to the 'lower' DBP target (RR 0.73, 95% CI 0.53 to 1.01), mainly due to a trend to lower non-cardiovascular mortality. There was no difference in stroke (RR 0.67, 95% CI 0.42 to 1.05), in myocardial infarction (RR 0.95, 95% CI 0.64 to 1.40) or in congestive heart failure (RR 1.06, 95% CI 0.58 to 1.92), low quality evidence. End-stage renal failure and total serious adverse events were not reported in any of the trials. A sensitivity analysis of trials comparing DBP targets < 80 mmHg (as suggested in clinical guidelines) versus < 90 mmHg showed similar results. There was a high risk of selection bias for every outcome analyzed in favor of the 'lower' target in the trials included for the analysis of DBP targets.

Authors' conclusions

At the present time, evidence from randomized trials does not support blood pressure targets lower than the standard targets in people with elevated blood pressure and diabetes. More randomized controlled trials are needed, with future trials reporting total mortality, total serious adverse events as well as cardiovascular and renal events.

Plain language summary

Blood pressure targets in people with diabetes

Review Question

We conducted this review to find and assess all trials designed to evaluate whether lower blood pressure targets are better than standard blood pressure targets for people with diabetes. We found and analyzed five studies.

Background

Cardiovascular disease is a frequent complication in people with diabetes. Hypertension (high blood pressure) is frequently found in people with diabetes. Recent clinical guidelines have recommended stricter control of blood pressure in people with diabetes compared with those without. For the general population of people with hypertension, the standard target has been to achieve a blood pressure of less than 140 to 160/90 to 100 mmHg, whereas for people with diabetes the guidelines have recommended lowering this target to less than 130/80 mmHg. This trend has been based on the assumption that achieving a lower blood pressure will produce a greater reduction in cardiovascular events.

Study Characteristics

The evidence is current to October 2013. We found and analyzed five randomized trials including 7134 adult participants with type 2 diabetes and high blood pressure, 40-80 years old, who received treatment aimed to lower blood pressure to a standard compared to a lower blood pressure target and followed for 2 to 5 years to detect differences in mortality and adverse events. Four out of five studies were funded by the drug manufacturer, which had a potential of impacting the results. One study was sponsored by the National Heart, Lung, and Blood Institute (NHLBI) from the United States.

Key Results

The only significant benefit in the group assigned to 'lower' systolic blood pressure was a small reduction in the incidence of stroke, but with a significantly larger increase in the number of other serious adverse events. The effect of systolic blood pressure targets on mortality was compatible with both a reduction and increase in risk. There was no benefit associated with a 'lower' diastolic blood pressure target.

The evidence from randomized trials available at the present time is of low quality and does not support blood pressure targets lower than the standard in people with raised blood pressure and diabetes. Further research is likely to change these results and future studies should report all outcomes that are important to patients, such as mortality and adverse events.

Ringkasan bahasa mudah

Sasaran tekanan darah bagi orang yang mempunyai diabetes.

Soalan ulasan

Kami membuat ulasan ini untuk mencari dan menilai semua kajian yang direka untuk menilai sama ada sasaran tekanan darah yang lebih rendah adalah lebih baik daripada sasaran tekanan darah standard untuk pesakit diabetes. Kami mendapati dan menganalisis lima kajian.

Latar belakang

Penyakit kardiovaskular adalah satu komplikasi yang kerap berlaku dalam orang yang menghidap diabetes. Hipertensi (tekanan darah tinggi) sering dikesan dalam orang dengan diabetes. Garis panduan klinikal terkini telah mengesyorkan kawalan tekanan darah yang lebih ketat dalam kalangan pesakit diabetes berbanding dengan mereka yang tidak mempunyai penyakit ini. Untuk orang awam dengan hipertensi, sasaran tekanan darah standard adalah untuk mencapai tekanan darah kurang daripada 140 hingga 160/90-100 mmHg, manakala bagi mereka yang menghidap diabetes, garis panduan telah mengesyorkan pengurangan sasaran ini kepada kurang daripada 130/80 mmHg . Trend ini berdasarkan anggapan bahawa pencapaian tekanan darah yang lebih rendah akan menghasilkan pengurangan yang lebih besar dalam kejadian kardiovaskular.

Ciri-ciri kajian

Bukti adalah terkini sehingga Oktober 2013. Kami mendapati dan menganalisis lima kajian rawak yang melibatkan 7134 orang peserta dewasa yang menghidap diabetes jenis 2 dan tekanan darah tinggi, berumur 40-80 tahun, menerima rawatan yang bertujuan untuk menurunkan tekanan darah sehingga standard berbanding dengan sasaran tekanan darah yang lebih rendah dan disusul untuk 2 hingga 5 tahun bagi mengesan perbezaan dalam mortaliti dan kesan buruk. Empat daripada lima kajian dibiayai oleh pengilang ubat yang mempunyai potensi untuk memberi kesan kepada keputusan. Satu kajian telah ditaja oleh 'National Heart, Lung, and Blood Institute (NHLBI)' dari Amerika Syarikat.

Keputusan utama

Satu-satunya manfaat signifikan dalam kumpulan yang diperuntukkan untuk 'menurunkan' tekanan darah sistolik adalah pengurangan kecil dalam insiden strok, tetapi mereka menunjukkan peningkatan yang lebih besar dalam bilangan kesan buruk lain yang serius. Kesan sasaran tekanan darah sistolik adalah serasi dengan pengurangan dan juga peningkatan dalam risiko mortaliti. Tiada manfaat ditunjukkan oleh sasaran tekanan darah diastolik 'yang lebih rendah'.

Bukti daripada kajian rawak sedia ada pada masa ini berkualiti rendah dan tidak menyokong sasaran tekanan darah lebih rendah daripada standard dalam kalangan orang yang mempunyai tekanan darah tinggi dan diabetes. Penyelidikan lanjut mungkin mengubah keputusan ini dan kajian masa depan harus melaporkan hasil yang penting kepada pesakit, seperti mortaliti dan kesan buruk.

Catatan terjemahan

Diterjemahkan oleh Ng Chia Shyn (International Medical University). Disunting oleh Noorliza Mastura Ismail (Kolej Perubatan Melaka-Manipal). Untuk sebarang pertanyaan berkaitan terjemahan ini sila hubungi Ng.ChiaShyn@student.imu.edu.my.

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