Therapeutics
Review: In patients with mild hypertension and no CV disease, BP-lowering drugs reduce stroke and mortality Clinical impact ratings:
多多多多多多夞
Sundstro¨m J, Arima H, Jackson R, et al; Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis. Ann Intern Med. 2015;162:184-91.
多多多多多多夞
Question
*Information provided by author.
In patients with mild hypertension and no cardiovascular (CV) disease, do blood pressure (BP)–lowering drugs reduce major CV events?
†Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev. 2012;8: CD006742.
Review scope
Sources of funding: Swedish Heart-Lung Foundation; Swedish Research Council; Australian Research Council; National Health and Medical Research Council of Australia.
Included studies had duration ≥ 1 year; compared BP-lowering drugs, alone or as part of a stepped-care approach, with placebo or less-intensive BP-lowering regimens in patients ≥ 18 years of age who had mild hypertension (systolic BP 140 to 159 mm Hg or diastolic BP 90 to 99 mm Hg) and no previous CV disease; and reported ≥ 1 event for an outcome of interest. Trials were included if ≥ 80% of patients had mild hypertension {or data were available for subgroups with mild hypertension}*. Outcomes included coronary events (coronary heart disease death or nonfatal myocardial infarction), stroke (cerebrovascular death or nonfatal stroke), heart failure (resulting in hospitalization or death), CV death, all-cause mortality, and withdrawals due to adverse events.
For correspondence: Dr. J. Sundstro¨m, Uppsala University, Uppsala, Sweden. E-mail [email protected].
Commentary The question addressed in the review by Sundstro¨m and colleagues is important because about 1 billion people have hypertension (1), and many have stage 1. A 2012 Cochrane review by Diao and colleagues reached the disappointing conclusion that treating mild hypertension for 4 to 5 years does not reduce mortality or CV events (2). However, that review included only 4 trials, published between 1978 and 1991, and had no patients with diabetes. The main drugs evaluated were limited to thiazides, propranolol, and reserpine.
Review methods MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials (May 2011 to Jun 2014) and a previous systematic review† (search to May 2011) were searched for randomized controlled trials (RCTs). Individual patient data from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) dataset were evaluated. 3 RCTs (n = 8905, 0 had diabetes mellitus, 0 had previous antihypertensive treatment, follow-up 4 to 5 y) identified in the systematic review and 10 comparisons from 8 RCTs in the BPLTTC dataset (n = 6361, mean age 64 y, 96% had diabetes mellitus, 61% had previous antihypertensive treatment, mean body mass index 29, median follow-up 4.4 y) met the inclusion criteria. RCTs compared BP-lowering drugs with placebo (n = 14 457) or compared more- with less-intensive BPlowering regimens (n = 809). All RCTs used allocation concealment and had adequate outcome data, 8 blinded patients and investigators, and 10 blinded outcome assessors.
Sundstro¨m and colleagues expand the previous review by adding 6361 patients from 8 RCTs from the BPLTTC dataset, all of which were published between 1998 and 2007, and 6 of which had placebo controls. Statistical power was enhanced by the greater number of patients (15 266 vs 8912), CV events (661 vs 165), and deaths (665 vs 167). The additional trials better reflect current practice as they include patients with diabetes and add angiotensin-converting enzyme inhibitors and calcium-channel blockers to the mix. In contrast to the 2012 review, Sundstro¨m and colleagues conclude that BP reduction of only 3.6/2.4 mm Hg is associated with fewer strokes, CV deaths, and total deaths. However, the number needed to treat (NNT) to prevent 1 additional stroke at 4 to 5 years was large (173) and had wide confidence intervals.
Main results The main results are in the Table.
Conclusion
Primary prevention is labor-intensive. The lower the baseline risk, the higher the NNT. A placebo-controlled trial assessing treatment of mild hypertension will probably never be done. Thousands of patients would need to be followed for many years to accrue enough events to draw firm conclusions about mortality. Therefore, we must rely on this type of meta-analysis and hope that its encouraging findings reflect reality: Treating mild hypertension does help. Whether it helps enough to make bearing the cost, burden, and adverse effects of treatment worthwhile is a deBP-lowering drugs vs placebo or more- vs less-intensive BP-lowering cision that patients and their physicians should regimens (active vs control) in mild hypertension without CV disease‡ share.
In patients with mild hypertension and no diagnosed cardiovascular disease, blood pressure–lowering drugs (vs placebo or less-intensive regimens) reduce stroke and mortality.
Outcomes
Number of trials (n)
Weighted event rates
At 4 to 5 y
Active
Control
RRR (95% CI)
Coronary events
8 (12 925)
2.6%
2.8%
8.8% (⫺12 to 25)
Not significant
Stroke
9 (12 411)
1.5%
2.1%
28% (6 to 44)
173 (108 to 810)
Heart failure
6 (5629)
2.3%
2.8%
20% (⫺12 to 42)
Not significant
CV death
6 (5881)
3.3%
4.4%
24% (2 to 42)
95 (55 to 1188)
10 (15 239)
3.8%
4.8%
21% (8 to 32)
99 (66 to 273)
RRI (CI)
NNH (CI)
102% (38 to 196)
36 (23 to 75)
All-cause mortality
Withdrawal due to adverse event
1 (2738)
5.6%
2.8%
Michael Tanner, MD New York University School of Medicine New York, New York, USA
NNT (CI) References
1. Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365: 217-23. 2. Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev. 2012; 8:CD006742.
‡BP = blood pressure; CV = cardiovascular; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rates and odds ratios in article; RRI, NNH, and CI calculated from event rates in article.
19 May 2015 Annals of Internal Medicine ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/22/2015
JC5
姝 2015 American College of Physicians
Review: In patients with mild hypertension and no CV disease, BP-lowering drugs reduce stroke and mortality Clinical impact ratings:
多多多多多多夞
Sundstro¨m J, Arima H, Jackson R, et al; Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis. Ann Intern Med. 2015;162:184-91.
多多多多多多夞
Question
*Information provided by author.
In patients with mild hypertension and no cardiovascular (CV) disease, do blood pressure (BP)–lowering drugs reduce major CV events?
†Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev. 2012;8: CD006742.
Review scope
Sources of funding: Swedish Heart-Lung Foundation; Swedish Research Council; Australian Research Council; National Health and Medical Research Council of Australia.
Included studies had duration ≥ 1 year; compared BP-lowering drugs, alone or as part of a stepped-care approach, with placebo or less-intensive BP-lowering regimens in patients ≥ 18 years of age who had mild hypertension (systolic BP 140 to 159 mm Hg or diastolic BP 90 to 99 mm Hg) and no previous CV disease; and reported ≥ 1 event for an outcome of interest. Trials were included if ≥ 80% of patients had mild hypertension {or data were available for subgroups with mild hypertension}*. Outcomes included coronary events (coronary heart disease death or nonfatal myocardial infarction), stroke (cerebrovascular death or nonfatal stroke), heart failure (resulting in hospitalization or death), CV death, all-cause mortality, and withdrawals due to adverse events.
For correspondence: Dr. J. Sundstro¨m, Uppsala University, Uppsala, Sweden. E-mail [email protected].
Commentary The question addressed in the review by Sundstro¨m and colleagues is important because about 1 billion people have hypertension (1), and many have stage 1. A 2012 Cochrane review by Diao and colleagues reached the disappointing conclusion that treating mild hypertension for 4 to 5 years does not reduce mortality or CV events (2). However, that review included only 4 trials, published between 1978 and 1991, and had no patients with diabetes. The main drugs evaluated were limited to thiazides, propranolol, and reserpine.
Review methods MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials (May 2011 to Jun 2014) and a previous systematic review† (search to May 2011) were searched for randomized controlled trials (RCTs). Individual patient data from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) dataset were evaluated. 3 RCTs (n = 8905, 0 had diabetes mellitus, 0 had previous antihypertensive treatment, follow-up 4 to 5 y) identified in the systematic review and 10 comparisons from 8 RCTs in the BPLTTC dataset (n = 6361, mean age 64 y, 96% had diabetes mellitus, 61% had previous antihypertensive treatment, mean body mass index 29, median follow-up 4.4 y) met the inclusion criteria. RCTs compared BP-lowering drugs with placebo (n = 14 457) or compared more- with less-intensive BPlowering regimens (n = 809). All RCTs used allocation concealment and had adequate outcome data, 8 blinded patients and investigators, and 10 blinded outcome assessors.
Sundstro¨m and colleagues expand the previous review by adding 6361 patients from 8 RCTs from the BPLTTC dataset, all of which were published between 1998 and 2007, and 6 of which had placebo controls. Statistical power was enhanced by the greater number of patients (15 266 vs 8912), CV events (661 vs 165), and deaths (665 vs 167). The additional trials better reflect current practice as they include patients with diabetes and add angiotensin-converting enzyme inhibitors and calcium-channel blockers to the mix. In contrast to the 2012 review, Sundstro¨m and colleagues conclude that BP reduction of only 3.6/2.4 mm Hg is associated with fewer strokes, CV deaths, and total deaths. However, the number needed to treat (NNT) to prevent 1 additional stroke at 4 to 5 years was large (173) and had wide confidence intervals.
Main results The main results are in the Table.
Conclusion
Primary prevention is labor-intensive. The lower the baseline risk, the higher the NNT. A placebo-controlled trial assessing treatment of mild hypertension will probably never be done. Thousands of patients would need to be followed for many years to accrue enough events to draw firm conclusions about mortality. Therefore, we must rely on this type of meta-analysis and hope that its encouraging findings reflect reality: Treating mild hypertension does help. Whether it helps enough to make bearing the cost, burden, and adverse effects of treatment worthwhile is a deBP-lowering drugs vs placebo or more- vs less-intensive BP-lowering cision that patients and their physicians should regimens (active vs control) in mild hypertension without CV disease‡ share.
In patients with mild hypertension and no diagnosed cardiovascular disease, blood pressure–lowering drugs (vs placebo or less-intensive regimens) reduce stroke and mortality.
Outcomes
Number of trials (n)
Weighted event rates
At 4 to 5 y
Active
Control
RRR (95% CI)
Coronary events
8 (12 925)
2.6%
2.8%
8.8% (⫺12 to 25)
Not significant
Stroke
9 (12 411)
1.5%
2.1%
28% (6 to 44)
173 (108 to 810)
Heart failure
6 (5629)
2.3%
2.8%
20% (⫺12 to 42)
Not significant
CV death
6 (5881)
3.3%
4.4%
24% (2 to 42)
95 (55 to 1188)
10 (15 239)
3.8%
4.8%
21% (8 to 32)
99 (66 to 273)
RRI (CI)
NNH (CI)
102% (38 to 196)
36 (23 to 75)
All-cause mortality
Withdrawal due to adverse event
1 (2738)
5.6%
2.8%
Michael Tanner, MD New York University School of Medicine New York, New York, USA
NNT (CI) References
1. Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365: 217-23. 2. Diao D, Wright JM, Cundiff DK, Gueyffier F. Pharmacotherapy for mild hypertension. Cochrane Database Syst Rev. 2012; 8:CD006742.
‡BP = blood pressure; CV = cardiovascular; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rates and odds ratios in article; RRI, NNH, and CI calculated from event rates in article.
19 May 2015 Annals of Internal Medicine ACP Journal Club Downloaded From: http://annals.org/ by a Penn State University Hershey User on 05/22/2015
JC5
姝 2015 American College of Physicians
