Blood pressure targets for the treatment of people with hypertension and cardiovascular disease

Luis Carlos Saiz; Javier Gorricho; Javier Garjón; Mª Concepción Celaya; Juan Erviti; Leire Leache

doi:10.1002/14651858.CD010315.pub3

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Figure 1

Results of the search.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 3

Forest plot of comparison: 1 Lower versus standard, outcome: 1.1 Total mortality.

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Figure 4

Forest plot of comparison: 1 Lower versus standard, outcome: 1.2 Serious adverse events.

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Figure 5

Forest plot of comparison: 1 Lower versus standard, outcome: 1.3 Cardiovascular events.

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Figure 6

Forest plot of comparison: 1 Lower versus standard, outcome: 1.4 Cardiovascular mortality.

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Analysis 1.1

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 1 Total mortality.

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Analysis 1.2

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 2 Serious adverse events.

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Analysis 1.3

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 3 Cardiovascular events.

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Analysis 1.4

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 4 Cardiovascular mortality.

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Analysis 1.5

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 5 Withdrawals due to adverse effects.

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Analysis 1.6

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 6 Blood pressure target achieved at 1 year.

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Analysis 1.7

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 7 Systolic blood pressure change from baseline at end of 1 year.

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Analysis 1.8

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 8 Diastolic blood pressure change from baseline at end of 1 year.

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Analysis 1.9

Comparison 1 Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease, Outcome 9 Number of antihypertensive drugs needed at the end of study.

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Summary of findings for the main comparison. Lower blood pressure targets compared with standard blood pressure targets for mortality and morbidity

Lower blood pressure targets compared with standard blood pressure targets for mortality and morbidity
Patient or population: cardiovascular disease with high blood pressure Setting: outpatients (average duration of trials 4 years) Intervention: lower blood pressure targets (≤ 135/85 mmHg) Comparison: standard blood pressure targets (≤ 140 to 160/90 to 100 mmHg)
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with standard blood pressure target	Risk with lower blood pressure target
Total mortality	Study population		RR 1.06 (0.91 to 1.23)	9484 (6 RCTs)	⊕⊕⊕⊝ MODERATE^a
	68 per 1000	72 per 1000 (62 to 84)
Serious adverse events	Study population		RR 1.01 (0.94 to 1.08)	9484 (6 RCTs)	⊕⊕⊝⊝ LOW^a,b
	252 per 1000	255 per 1000 (237 to 272)
Total cardiovascular events	Study population		RR 0.89 (0.80 to 1.00)	9484 (6 RCTs)	⊕⊕⊝⊝ LOW^a,c
	127 per 1000	113 per 1000 (102 to 127)
Cardiovascular mortality	Study population		RR 1.03 (0.82 to 1.29)	9484 (6 RCTs)	⊕⊕⊕⊝ MODERATE^a
	31 per 1000	32 per 1000 (25 to 40)
Withdrawals due to adverse effects	Study population		RR 8.16 (2.06 to 32.28)	690 (2 RCT)	⊕⊝⊝⊝ VERY LOW^a,d
	7 per 1000	60 per 1000 (15 to 239)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High quality: we are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect
^aDowngraded one level owing to serious imprecision (95% CI is wider than the minimal important difference). ^bDowngraded one level owing to incomplete available data. ^cDowngraded one level owing to high risk of bias. ^dDowngraded two levels because only two of the smaller studies reported this outcome.

Summary of findings for the main comparison. Lower blood pressure targets compared with standard blood pressure targets for mortality and morbidity

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Table 1. Baseline characteristics of included study participants

Mean (SD) unless otherwise stated	AASK 2002	ACCORD BP 2010	HOT 1998	Past BP 2016	SPRINT 2015	SPS3 2013
Number of participants	155	1531	3232	295	1562	2709
Sex (% male)	68%	63%	53%	64%	76%	62%
Age in years	57 (9)	62 (8)	62 (‐)	71 (9)	70 (9)	63 (11)
Ethnic group (% Caucasian)	0%	62%	92%	98%	71%	53%
Diabetes	0%	100%	12%	10%	0%	36%
Current smoker	31%	13%	16%	13%	14%	20%
Systolic blood pressure	149 (28)	138 (16)	174 (15)	143 (14)	138 (16)	146 (18)
Diastolic blood pressure	93 (16)	74 (11)	106 (3)	80 (10)	74 (12)	79 (11)
Ischemic heart disease (IHD)	25%	86%	95%	22%	‐‐‐	11%
Stroke	69%	20%	7%	85%	0%	99%
Peripheral vascular disease	23%	‐‐‐	‐‐‐	7%	‐‐‐	‐‐‐
Thiazides	‐‐‐	51%	‐‐‐	35%	‐‐‐	35%
ACEI/ARB	‐‐‐	84%	‐‐‐	65%	‐‐‐	71%
Calcium channel blocker	‐‐‐	26%	‐‐‐	43%	‐‐‐	28%
Beta blocker	‐‐‐	57%	‐‐‐	20%	‐‐‐	27%
Other antihypertensive drugs	‐‐‐	28%	‐‐‐	11%	‐‐‐	8%
Number of antihypertensive drugs	‐‐‐	3.0 (1.4)	1.0 (‐‐)	1.1 (0.8)	2.1 (1.0)	1.7 (1.1)
(‐‐) no information is available. Ischemic heart disease, stroke, and peripheral vascular disease percentages are totally independent of each other because participants can have more than one cardiovascular event at the same time. A similar explanation can be offered with respect to percentages in the different classes of antihypertensive drugs. Abbreviations: ACEI: angiotensin‐converting enzyme inhibitor; ARB: angiotensin receptor blocker; IHD: ischemic heart disease; SD: standard deviation.

Table 1. Baseline characteristics of included study participants

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Table 2. Lower versus standard blood pressure target; people with diabetes, difference in targets ≥ 10 mmHg

Outcome	Studies	Participants	Statistical Method	Effect Estimate
Total mortality	ACCORD BP 2010, HOT 1998, SPS3 2013	2773	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.91,1.45]
Cardiovascular mortality	ACCORD BP 2010, HOT 1998, SPS3 2013	2773	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.69,1.39]
Cardiovascular events	ACCORD BP 2010, HOT 1998, SPS3 2013	2773	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.74,1.03]
Serious adverse events	ACCORD BP 2010, HOT 1998, SPS3 2013	2773	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.88,1.15]

Table 2. Lower versus standard blood pressure target; people with diabetes, difference in targets ≥ 10 mmHg

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Comparison 1. Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total mortality Show forest plot	6	9484	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.91, 1.23]

2 Serious adverse events Show forest plot	6	9484	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.94, 1.08]

2.1 Total serious adverse events	1	1562	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.91, 1.09]
2.2 Subset of total serious adverse events	5	7922	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.92, 1.11]
3 Cardiovascular events Show forest plot	6	9484	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.80, 1.00]

4 Cardiovascular mortality Show forest plot	6	9484	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.82, 1.29]

5 Withdrawals due to adverse effects Show forest plot	2	690	Risk Ratio (M‐H, Fixed, 95% CI)	8.16 [2.06, 32.28]

6 Blood pressure target achieved at 1 year Show forest plot	6	8588	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [1.17, 1.24]

7 Systolic blood pressure change from baseline at end of 1 year Show forest plot	6	8546	Mean Difference (IV, Random, 95% CI)	‐8.90 [‐13.24, ‐4.56]

8 Diastolic blood pressure change from baseline at end of 1 year Show forest plot	6	8546	Mean Difference (IV, Random, 95% CI)	‐4.50 [‐6.35, ‐2.65]

9 Number of antihypertensive drugs needed at the end of study Show forest plot	5	7910	Mean Difference (IV, Random, 95% CI)	0.56 [0.16, 0.96]

Comparison 1. Lower versus standard blood pressure targets for people with hypertension and history of cardiovascular disease

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