Health Outcomes Associated With Various Antihypertensive Therapies Used as First-Line Agents

Abstract

N 1993 AND AGAIN IN 1997, THE Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure recommended low-dose diuretics and ␤-blockers as first-line treatment for patients with uncomplicated hypertension. 1,2 This recommendation reflected the wealth of clinical trial evidence about the health benefits associated with lowdose diuretics and ␤-blockers. [3][4][5][6][7][8] The early trials of diuretics and ␤-blockers had generally randomized patients with high blood pressure to active therapy or to placebo. Early answers were clearest for patients with the highest level of blood pressure. 4,5 These studies answered the question of whether several specific antihypertensive treatments improved health outcomes.Clear evidence of health benefits associated with diuretics and ␤-blockers precluded further long-term placebocontrolled trials. Thus, the recent large long-term trials have evaluated one active treatment against another active treatment in terms of their ability to prevent cardiovascular events. [9][10][11][12][13][14][15] In these Author Affiliations and Financial Disclosures are listed at the end of this article.

Between-country variation in the utilization of antihypertensive agents: guidelines and clinical practice

“…Thiazide diuretics are recommended in all included guidelines as a valid first choice, they have a long track record, are costeffective and are supported by solid evidence. 23 However, they also show the largest variation in use, indicating strong variability in acceptance in clinical practice across the six studied countries. The variation in utilization for this class remains large even when the use of thiazide diuretics in combination preparations, that is, together with an angiotensin II receptor blocker or an ACE-inhibitor, is taken into consideration.…”

Beta-receptor blockers in primary prevention for cardiovascular disease: forgotten benefits?

“…Previous studies of this kind has documented that beta-receptor blockers seem to be less efficient in elderly subjects 24,25 based on a number of studies available in the late 1990s. This was also highlighted in one meta-analysis of Pahor et al, 26 but not as evident in another meta-analysis of the Blood Pressure Trialist Collaboration in 2003. 27 The question whether beta-receptor blockers are less effective in the elderly, therefore, still has to be proven.…”

The place of diuretics in preventing cardiovascular events

“…Doses equivalent to 12.5 up to 25 mg of hydrochlorothiazide (HCTZ) (which is well met by indapamide 1.5 mg, sustained release) clearly are as effective as any of the other major classes of drugs. 3 However, larger doses, equivalent to 50 mg or more of HCTZ, have not been found to provide the degree of cardiovascular protection that would be expected from their antihypertensive effect. 4 There are multiple reasons why high doses may be counterproductive.…”

“…In this meta-analysis, all published randomized controlled trails (RCTs) from 1967 to early 2003 were examined, combining data from 42 trials that included over 190 000 patients. 3 In the Blood Pressure Lowering Treatment Trialists Collaboration, only those RCTs published since 1995 were included, including data from 29 trials covering over 160 000 patients. Since the RCTs comparing diuretics with placebo were all published before 1995, the Trialists' meta-analysis did not portray the evidence that diuretics were superior to placebo.…”

“…CHD indicates coronary heart disease; CHF, congestive heart failure; CI, confidence interval; CVD, cardiovascular disease; and RR, relative risk (modified from Psaty BM et al). 3 140/90 mmHg, 65% of the enrollees ended up on two or more drugs, although few were given one of the other comparator classes. Thus, all of the data such as portrayed in both of the recent metaanalyses 3,6 must be recognized as evidence of the value of therapy that is based on one or another drug but not purely derived from the effect of a single agent.…”