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GEM - hypertension evidence base

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Hypertension - trial evidence



vidence relating to systolic hypertension


  • i
  • first-line treatment of isolated systolic hypertension is a thiazide diuretic or calcium antagonist
    • what level of systolic hypertension would the trial evidence suggest benefit for treatment?


Angiotensin-Converting Enzyme (ACE) inhibitors in hypertension management

  • contrasting evidence exists for the use of ACE inhibitors for hypertension. Two important trails in the 1990s were the Captopril Prevention Project and the STOP-2 trial.
    • the Captopril Prevention Project concluded that
      • there were no significant differences in cardiovascular mortality and morbidity between captopril and conventional treatments
      • however the study data suggested that captopril was less protective against stroke than was treatment with beta blockers or diuretics or both
      • GPnotebook reference
    • STOP-2 trial did not find differences in stroke mortality comparing ACE inhibitors to other antihypertensive treatments in the treatment of systolic hypertension
    • more recently the ASCOT trial investigators
      • in this trial management of hypertension was based on stepped regimens of a beta-blocker (atenolol) and a thiazide diuretic, or a calcium channel blocker (amlodipine) and an ACE inhibitor, with further addition of doxazosin, if necessary, to achieve blood pressure
      • there were significant differences in favour of the amlodipine and ACE inhibitor group found in most secondary endpoints including CV mortality, strokes, and CV events plus procedures
        • was the primary endpoint achieved in this study?
        • in which treatment group was new-onset diabetes more common?
        • could the difference in outcomes between the two groups, with respect to secondary endpoints, be explained by differences in blood pressure between the two groups?

ACE inhibitors to reduce the risk of cardiovascular disease

Two important trials have shown benefit in terms of reduction of risk of cardiovascular disease in patients at high risk

HOPE study

  • which ACE inhibitor was used in the HOPE study?
  • did the use of vitamin E reduce the risk of cardiovascular disease?
  • did the use of an ACE inhibitor reduce risk of cardiovascular disease?
  • the micro-HOPE study investigated the use of an ACE inhibitor in diabetic patients with another cardiovascular risk factor

EUROPA study

  • which ACE inhibitor was investigated in the EUROPA study?
  • the use of an ACEI showed benefit, like the HOPE study, irrespective of cardiac function

Alpha blockers in hypertension

  • what was the concern regarding use of alpha blockers that was produced in the ALLHAT study?

Hypertension and Lipids

There is evidence of benefit for the treatment of raised lipids in the context of hypertension.


ALLHAT however did not show benefit of lipid lowering treatment in the context of patients with hypertension. After six years follow-up, results only revealed a small non-significant reduction in CHD event rates with pravastatin (9.3% vs. 10.4% RR=0.91, p=0.16) and no reduction in deaths

The major benefits in terms of lipid lowering have been in patients at high risk of cardiovascular disease. An important trial in this context is the Heart Protection Study

Aspirin in hypertension


Which study revealed the benefit of using aspirin in patients with controlled hypertension?

Angiotensin Receptor Blockers in Hypertension


The LIFE study was a landmark study in terms of using angiotensin receptor blockers in hypertension. Which other treatment used in this study was associated with an increased incidence of new onset diabetes during the study?

The VALUE study also is an important study in the context of hypertension and use of angiotensin receptor blockers. In this study there was also a reduced incidence of new onset diabetes in the angiotensin receptor blocker treated group. What was the comparitor class of drug that had the higher incidence of new onset diabetes during the study?







  • results of clinical trials have determined the pragmatic definition of hypertension: ‘‘the level of blood pressure at which there is evidence that blood pressure reduction does more good (in terms of reducing CVD risk) than harm’’
    • hypertension based on clinical blood pressure readings is defined in adults (aged > 18 years) as a systolic blood pressure > =140 mm Hg and/or a diastolic blood pressure > =90 mm Hg

  • the authors of the Joint British Guidelines have emphasised the importance of reducing blood pressure per se, irrespective of drug class used
    • the JBS2 guidelines state that "meta-analyses and systematic reviews have consistently demonstrated that no one class of blood pressure lowering drug is any more effective than another at preventing CHD in people with treated hypertension—the benefit of treatment in preventing CHD being driven by the quality of blood pressure control.."




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