Thiazides best first choice for hypertension

Wright JM, Musini VM

Published Online:

July 8, 2009

One of the most important decisions in treating people with elevated blood pressure is what drug class is used first. This decision has enormous consequences in terms of health outcomes and cost. In this review health outcomes resulting from 4 drug classes are summarized. Most of the evidence demonstrated that first-line low-dose thiazides reduce mortality and morbidity (stroke, heart attack and heart failure). No other drug class improved health outcomes better than low-dose thiazides, and beta-blockers and high-dose thiazides were inferior. Low-dose thiazides should be the first choice drug in most patients with elevated blood pressure. Fortunately, thiazides are also very inexpensive.

Abstract (click to read)

Background:

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.

Objectives:

Primary objective: 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).

Search strategy:

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.

Selection criteria:

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.

Data collection and analysis:

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.

Main results:

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.

Authors' conclusions:

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.

This record should be cited as:

Wright JM, Musini VM. First-line drugs for hypertension. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD001841. DOI: 10.1002/14651858.CD001841.pub2

Assessed as up to date:

April 1, 2009

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Primary Review Group:

Hypertension Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

What are the most effective first-line antihypertensive drugs?

Bottom line:

First-line low-dose thiazides (eg, hydrochlorothiazide <50mg) are more effective than first-line high-dose thiazides (eg, hydrochlorothiazide 50mg or more) and first-line beta-blockers, in reducing mortality and morbidity (stroke, myocardial infarction and heart failure). For total cardiovascular events over 5 years, the NNT* is 20 in moderate to severe hypertension (>160/100mmHg) and the NNT is 120 in mild hypertension (140-160/90-100mmHg). Evidence for first-line ACE inhibitors is similar to low-dose thiazides but less robust, and ACE inhibitors are more expensive than thiazides. Evidence for first-line calcium channel blockers is insufficient. *NNT = number needed to treat to benefit 1 individual.

Caveat:

Over 72% of participants in this review represent a primary prevention population.There are no randomised controlled trials comparing first-line use of other classes of drugs, such as angiotensin receptor blockers or alpha blockers.

Context:

One of the major decisions involved in the management of patients with elevated blood pressure is which drug to choose first. The decision should be informed by the best available evidence of reduction of the outcomes that are important to the patient, ie, the ability of the drug to reduce the adverse health outcomes associated with elevated blood pressure (stroke, myocardial infarction and mortality).

Cochrane Systematic Review:

Wright JM and Musini VM. First-line drugs for hypertension. Cochrane Reviews 2009, Issue 3. Article No. CD001841. DOI: 10.1002/14651858.CD001841.pub2. This review contains 57 studies involving 58,040 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Heart & circulation > Hypertension > Treatment: pharmacological

Kidney disease > Hypertension > Treatment: pharmacological

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Thiazides best first choice for hypertension

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