First-line drugs for hypertension (Review)

Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada, V6T 1Z3.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 01/2009; 164(3):CD001841. DOI: 10.1002/14651858.CD001841.pub2
Source: PubMed

ABSTRACT Sustained elevated blood pressure, unresponsive to lifestyle measures, leads to a critically important clinical question: What class of drug to use first-line? This review answers that question.

To quantify the benefits and harms of the major first-line anti-hypertensive drug classes: thiazides, beta-blockers, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, alpha-blockers, and angiotensin II receptor blockers (ARB).
Electronic search of MEDLINE (Jan. 1966-June 2008), EMBASE, CINAHL, the Cochrane clinical trial register, using standard search strategy of the hypertension review group with additional terms.
Randomized trials of at least one year duration comparing one of 6 major drug classes with a placebo or no treatment. More than 70% of people must have BP >140/90 mmHg at baseline.
The outcomes assessed were mortality, stroke, coronary heart disease (CHD), cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and withdrawals due to adverse drug effects. Risk ratio (RR) and a fixed effects model were used to combine outcomes across trials.
Of 57 trials identified, 24 trials with 28 arms, including 58,040 patients met the inclusion criteria. Thiazides (19 RCTs) reduced mortality (RR 0.89, 95% CI 0.83, 0.96), stroke (RR 0.63, 95% CI 0.57, 0.71), CHD (RR 0.84, 95% CI 0.75, 0.95) and CVS (RR 0.70, 95% CI 0.66, 0.76). Low-dose thiazides (8 RCTs) reduced CHD (RR 0.72, 95% CI 0.61, 0.84), but high-dose thiazides (11 RCTs) did not (RR 1.01, 95% CI 0.85, 1.20). Beta-blockers (5 RCTs) reduced stroke (RR 0.83, 95% CI 0.72, 0.97) and CVS (RR 0.89, 95% CI 0.81, 0.98) but not CHD (RR 0.90, 95% CI 0.78, 1.03) or mortality (RR 0.96, 95% CI 0.86, 1.07). ACE inhibitors (3 RCTs) reduced mortality (RR 0.83, 95% CI 0.72-0.95), stroke (RR 0.65, 95% CI 0.52-0.82), CHD (RR 0.81, 95% CI 0.70-0.94) and CVS (RR 0.76, 95% CI 0.67-0.85). Calcium-channel blocker (1 RCT) reduced stroke (RR 0.58, 95% CI 0.41, 0.84) and CVS (RR 0.71, 95% CI 0.57, 0.87) but not CHD (RR 0.77 95% CI 0.55, 1.09) or mortality (RR 0.86 95% CI 0.68, 1.09). No RCTs were found for ARBs or alpha-blockers.
First-line low-dose thiazides reduce all morbidity and mortality outcomes. First-line ACE inhibitors and calcium channel blockers may be similarly effective but the evidence is less robust. First-line high-dose thiazides and first-line beta-blockers are inferior to first-line low-dose thiazides.

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    • "Given the power of lifestyle in preventing and reversing as well as managing hypertension [1] [2], pressing questions that need to be addressed relate to maximizing these benefits and eliminating the need for drugs, augmenting them with medication if indicated, that is, which medication for which patient in the presence of lifestyle behavior change (e.g., smoking cessation, nutrition, and physical activity), and understanding how healthy lifestyles impact the pharmacokinetics of the medications of interest. A possible limitation of our analysis of the review by Wright and Musini [8] is that this Cochrane review is restricted to a subset of RCCTs, albeit it from a high quality established database; thus is not a comprehensive assessment of the methodology of all RCCTs investigating antihypertension drugs. Furthermore, although this review was published in 2009, some of the initial studies began as early as 1970. "
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    ABSTRACT: Established standards for first-line hypertension management include lifestyle modification and behavior change. The degree to which and how lifestyle modification is systematically integrated into studies of first-line drug management for hypertension is of methodological and clinical relevance. This study systematically reviewed the methodology of articles from a recent Cochrane review that had been designed to inform first-line medical treatment of hypertension and was representative of high quality established clinical trials in the field. Source articles (n = 34) were systematically reviewed for lifestyle interventions including smoking cessation, diet, weight loss, physical activity and exercise, stress reduction, and moderate alcohol consumption. 54% of articles did not mention lifestyle modification; 46% contained nonspecific descriptions of interventions. We contend that hypertension management research trials (including drug studies) need to elucidate the benefits and risks of drug-lifestyle interaction, to support the priority of lifestyle modification, and that lifestyle modification, rather than drugs, is seen by patients and the public as a priority for health professionals. The inclusion of lifestyle modification strategies in research designs for hypertension drug trials could enhance current research, from trial efficacy to clinical outcome effectiveness, and align hypertension best practices of a range of health professionals with evidence-based knowledge translation.
    01/2014; 2014:835716. DOI:10.1155/2014/835716
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