Beta-Blockers Versus Diuretics in Hypertensive Men: Main Results from the HAPPHY Trial

Wilhelmsen, Lars; Berglund, Göran; Elmfeldt, Dag; Fitzsimons, Timothy J.; Holzgreve, H; Hosie, J.; Hörnkvist, Per-Erik; Pennert, Kjell; Tuomilehto, J; Wedel, Hans

doi:10.1097/00004872-198710000-00009

Cited by 415 publications

(162 citation statements)

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“…This lends further evidence support to randomised controlled trials involving head-to-head comparison of the major antihypertensive drug classes that reported comparable mortality outcomes across classes. Important landmark trials, notably ALLHAT, 11 ANBP2, 12 INSIGHT, 13 HAPPHY, 14 MRC, 15 LIFE 16 and VALUE 17 unanimously reported that no single antihypertensive class is superior regarding association with mortality reduction, with the possible exception of ASCOT reporting a marginal favourable outcome of CCB (aOR 0.90, 95% CI 0.82, 0.99) compared with b-blockers. 26 These findings were also compatible with a meta-analysis of randomised controlled trials showing no clear difference between the effects of the drug classes on major CVS events.…”

Section: Interpretation and Relationship With Published Literaturesmentioning

confidence: 99%

“…[8][9][10] These position statements are supported by a large number of high-quality randomised controlled trials, which showed similar mortality rates among users of the major antihypertensive drug classes. [11][12][13][14][15][16][17] This finding is convincingly showed when the Blood Pressure Lowering Treatment Trialists Collaboration published their meta-analysis from 162 341 patients and reported no significant differences in total and CVS mortality among users of thiazide diuretics, b-blockers, calcium channel blockers (CCBs) and angiotensinconverting enzyme inhibitors (ACEIs). 18 However, some limitations of these trials have been raised, [19][20][21] including the need to select higherrisk patients and thus uncomplicated, younger and lower-risk patients were under-represented.…”

Section: Introductionmentioning

confidence: 99%

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Profiles of mortality among Chinese hypertensive patients in Hong Kong: a cohort study

et al. 2009

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We studied the profiles of all-cause and cardiovascular (CVS) mortality among users of different antihypertensive classes in a Chinese population. From electronic patient records, a cohort study was conducted among 18 338 patients who ever newly prescribed an a-blocker, thiazide diuretic, b-blocker, calcium channel blocker (CCB) or agents acting on the renin-angiotensin system (RAS) without drug discontinuation or switching in the public primary-care sector in a large Territory of Hong Kong during January 2004-June 2007. The odds ratios of mortality (all-cause and CVS) were evaluated according to the prescribed antihypertensive drug classes by Cox proportional hazards regression analyses. A total of 823 deaths (4.5%) were reported during the study period. The crude proportions of all-cause mortality were highest in a-blockers (6.2%) and CCB (5.7%), but lowest in b-blockers (2.8%). Compared with CCB, patients on thiazide diuretics were shown to have statistically significantly lower all-cause (adjusted hazard ratios (aHRs) 0.75, 95% CI 0.60, 0.93, P ¼ 0.010) and CVS mortality (aHR 0.40, 95% CI 0.21, 0.78, P ¼ 0.007), but the 95% CI of the odds ratios of the major drug classes overlapped. When each drug class was used as a reference group, or when patients with only uncomplicated hypertension were included, their respective 95% CI similarly overlapped. Antihypertensive drug classes were associated with statistically comparable odds of all-cause and CVS mortality. This finding from real-life clinical practice further supports the position statements from international guidelines, which recommend that the major antihypertensive drug classes are suitable for initiating pharmacotherapy for the management of hypertension.

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Section: Interpretation and Relationship With Published Literaturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Profiles of mortality among Chinese hypertensive patients in Hong Kong: a cohort study

et al. 2009

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“…Metoprolol reduced coronary events, 14 and sudden deaths 15 much more effectively than diuretics in the MAPHY Study and propranolol had some impact in the MRC study 16 when silent MIs were included. 17 However, atenolol was not very effective in the Cooper and Warrender Study, 18 the HAPPHY study 19,20 or the MRC elderly study. 10 These different results will be discussed below.…”

Section: Primary and Secondary Preventionmentioning

confidence: 99%

Beta-blockers: a time for reappraisal

Kendall

1998

J Hum Hypertens

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Claims could not easily be made that beta-blockers as a group are the most potent or best-tolerated antihypertensive drugs. However, they have a very important role in the management of hypertensive patients who are being treated to prevent cardiovascular complications. Whilst stroke incidence can be reduced by effective blood pressure control, preventing the progress of coronary artery disease to reduce the patients risk of having a myocardial infarct, dying suddenly or developing heart failure is more difficult. Beta-blockers, particularly

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“…For example, the Medical Research Council trial (MRC, using propranolol), the International Prospective Primary Prevention Study in Hypertension (IPPPSH, using exprenolol), and the Heart Attack Primary Prevention in Hypertension trial (HAPPHY, using atenolol, propranolol and metoprolol), almost uniformly showed no significant cardioprotective effect of beta-blockers. [1][2][3][4] Furthermore, a second large MRC trial of 4396 elderly hypertensives (mean age 70) found that randomisation to beta-blockers resulted in a worse outcome compared to treatment with diuretics, with a non-statistically significant trend toward fewer strokes, and no improvement in coronary disease or cardiovascular mortality. 5 By contrast, the incidence of stroke, coronary disease, and cardiovascular mortality was reduced by diuretics when compared to placebo (relative risk 0.6 to 0.7).…”

mentioning

confidence: 99%

“…However, the MAPHY study was actually a subset of the HAPPHY cohort which used atenolol, propranolol, and metoprolol and with no benefit. 3,4 Thus, all the beta-blockers may not be the same; a specific protective effect from metoprolol could even suggest that atenolol and propranolol have a deleterious effect on coronary disease! 16 The observation that carvediolol, a vasodilatating betablocker with antioxidant properties, has benefits in heart failure, where other agents such as atenolol do not, is further testimony to the differences between beta-blockers.…”

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confidence: 99%

Beta-blockers in hypertension: to reappraise or to call a halt?

Lip

1998

J Hum Hypertens

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Hypertension treatment guidelines, which have been formulated by the learned and the wise have long recommended the thiazide diuretics and betablockers as first-line drugs for the treatment of hypertension. They base this on the general 'understanding' that these agents have been around for a while and they are 'well established' to reduce heart attacks and strokes. As a pragmatic definition of hypertension is that level of blood pressure where treatment gives more benefit than harm, the use of drugs with a good track record is sound clinical practice. Is this 'understanding' that the thiazides and beta-blockers are good first-line drugs the wholehearted truth?In most of the early trials, patients with mild to moderate hypertension were randomised to therapy with a beta-blocker or a thiazide diuretic. For example, the Medical Research Council trial (MRC, using propranolol), the International Prospective Primary Prevention Study in Hypertension (IPPPSH, using exprenolol), and the Heart Attack Primary Prevention in Hypertension trial (HAPPHY, using atenolol, propranolol and metoprolol), almost uniformly showed no significant cardioprotective effect of beta-blockers. 1-4 Furthermore, a second large MRC trial of 4396 elderly hypertensives (mean age 70) found that randomisation to beta-blockers resulted in a worse outcome compared to treatment with diuretics, with a non-statistically significant trend toward fewer strokes, and no improvement in coronary disease or cardiovascular mortality. 5 By contrast, the incidence of stroke, coronary disease, and cardiovascular mortality was reduced by diuretics when compared to placebo (relative risk 0.6 to 0.7).A recent meta-analysis by Psaty et al 6 on 48 220 patients from long term, controlled clinical trials reported that beta-blocker therapy was effective in preventing stroke and congestive heart failure, with a relative risk reduction of 29% for stroke and 42% for congestive heart failure. Despite lowering blood pressure by an average of 5-6 mm Hg, neither betablocker therapy (nor for that matter, high dose Correspondence: Dr GYH Lip diuretic therapy) showed a significant reduction of coronary heart disease events. Total mortality reduction with beta-blockers was also not significant, and neither was cardiovascular mortality reduction. By contrast, low dose diuretic therapy resulted in a significant reduction in stroke (34%), coronary heart disease events (28%), congestive cardiac failure (42%), total mortality (10%) and cardiovascular mortality (24%), when compared to controls. 6 In a recent systematic review in the Journal of the American Medical Association by Messerli et al, 7 analysis of 10 trials involving 16 164 elderly hypertensive patients (aged у60 years) found that diuretic therapy was superior to beta-blockers in preventing cerebrovascular events (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.51-0.72), fatal stroke (OR 0.67, 95% CI 0.49-0.90), coronary heart disease (OR 0.74, 95% CI 0.64 -0.85), cardiovascular mortality (OR 0.75, 95% CI 0.64 -0.87) and a...

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Beta-Blockers Versus Diuretics in Hypertensive Men: Main Results from the HAPPHY Trial

Cited by 415 publications

References 0 publications

Profiles of mortality among Chinese hypertensive patients in Hong Kong: a cohort study

Profiles of mortality among Chinese hypertensive patients in Hong Kong: a cohort study

Beta-blockers: a time for reappraisal

Beta-blockers in hypertension: to reappraise or to call a halt?

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