UPPSALA, SWEDEN — Patients with mild hypertension (140 to 159 mm Hg/90 to 99 mm Hg) who received antihypertensive therapy lowered their blood pressure by about 3.6/2.4 mm Hg and had a reduced short-term risk of dying from stroke or cardiovascular disease, in a large meta-analysis[1] .
The review was published online December 22, 2014 in the Annals of Internal Medicine.
In more than 15 000 patients with mild hypertension and no known cardiovascular disease, those who were randomized to blood-pressure–lowering drug therapy had a 28% lower risk of stroke, a 25% lower risk of cardiovascular death, and a 22% lower risk of death compared with their peers, during a 5-year follow-up.
The meta-analysis included trials from an earlier review[2] that found no benefits for pharmacotherapy in mild hypertension plus trials from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC).
"We observed no heterogeneity in effects between BPLTTC studies and non-BPLTTC studies and interpret the differences in conclusions between our overview[1] and the one preceding it[2] as primarily attributable to statistical power," Dr Johan Sundström (Uppsala University, Sweden) told heartwire . "Our overview nearly doubles the number of patients, quadruples the number of cardiovascular events, and provides data on end points not available in the prior meta-analysis."
The blood-pressure reductions and number of events were small, Sundström conceded, so "a definitive, adequately powered, large-scale trial among patients with uncomplicated mild hypertension would be an important addition to the evidence base." However, "such a study is unlikely to ever happen, and this review provides the best summary of the available evidence."
Is Pharmacotherapy Warranted for Mild Hypertension?
About a billion people worldwide have hypertension, which is the main risk factor for early death, the researchers write. However, most people have mild hypertension with no overt CVD, and the optimal treatment strategy for them is "controversial," since drug trials generally enroll patients with more established hypertension.
The previous meta-analysis "was limited by the exclusion of many recent relevant trials, use of second-line treatment regimens, and low study power," Sundström and colleagues write.
To update the evidence, they performed a meta-analysis of three trials in the previous review (excluding one trial with seven participants and no events), plus 10 BPLTTC trials.
The non-BPLTTC trials were the Medical Research Council Trial of Treatment of Mild Hypertension (MRC), the Australian National Blood Pressure Study (ANBP), and the Veterans Administration-National Heart, Lung, and Blood Institute Feasibility Trial (VA-NHLBI), published from 1978 to 1985.
These trials compared bendrofluazide, propranolol, chlorothiazide, and chlorthalidone and reserpine vs placebo, in 8905 patients with mild hypertension but without diabetes or previous hypertensive therapy.
The BPLTTC trials were the Appropriate Blood Pressure Control in Diabetes (ABCD), Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), Bergamo Nephrologic Diabetes Complications Trial (BENEDICT), Non-insulin-dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR), Prevention of Atherosclerosis with Ramipril (PART-2) Prevention of Renal and Vascular End-Stage Disease Intervention Trial (PREVEND IT), Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT), and the UK Prospective Diabetes Study (UKPDS) trials, published from 1998 to 2007.
These trials compared perindopril, trandolapril, verapamil, ramipril, fosinopril vs placebo, and more vs less intensive therapy, in 6361 patients, of whom 61% had previous antihypertensive treatment and 96% had type 2 diabetes.
In the 7842 patients in the active-treatment arms of the 13 trials, there were 307 deaths, including 96 cardiovascular deaths. There were also 99 strokes, 185 coronary events, and 62 cases of heart failure.
In the 7424 patients in the control arms, there were 358 deaths, including 124 cardiovascular deaths. There were also 127 strokes, 179 coronary events, and 76 cases of heart failure.
Risk of Cardiovascular Outcome in Patients With Treated vs Non-treated Mild Hypertension*
| Outcome | Odds ratio (95% CI) |
| CV event | 0.86 (0.74–1.01) |
| Stroke | 0.72 (0.55–0.94) |
| Coronary event | 0.91 (0.71–1.12) |
| Heart failure | 0.80 (0.57–1.12) |
| CV deaths | 0.75 (0.57–0.98) |
| Total deaths | 0.78 (0.67–0.92) |
Withdrawal from treatment due to adverse effects was more common in the active groups.
"If we are to make a serious effort to fulfill the aim of the European Heart Health Charter that 'Every child born in the new millennium has the right to live until the age of at least 65 without suffering from avoidable cardiovascular disease,' we will have to start also giving younger adults at high risk of cardiovascular disease a chance of receiving optimal preventive treatment," he said. "Our review now demonstrates that blood-pressure–lowering therapy can be an effective part of that treatment regimen also, if the blood pressure is at the grade 1 hypertension level."
Treatment decisions in people with uncomplicated mild hypertension "should be based on a comprehensive risk assessment . . . preferably using a validated risk-estimation tool . . . to select people with the best chance of benefiting from blood-pressure–lowering treatment," he said.
Sundström received funding from the Swedish Heart-Lung Foundation and the Swedish Research Council. At its initiation, the BPLTTC received funding from Astra Hässle, Bayer, British Heart Foundation, Bristol-Myers Squibb, Glaxo Wellcome, Hoechst Marion Roussel, Knoll, Merck, Pfizer, Searle, and Institut de Recherches Internationales Servier. Disclosures for the coauthors are available on the journal's website.
Heartwire from Medscape © 2014 Medscape, LLC
Cite this: Marlene Busko. Drugs Benefit Mild Hypertension, Large Review Concludes - Medscape - Dec 22, 2014.
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