January 25th, 2011

New Study Finds Hydrochlorothiazide Inferior To All Other BP Drugs

At the dosages most often used, hydrochlorothiazide (HCTZ), the most widely used antihypertensive agent in the world, is “consistently inferior” to all other drugs, according to a new meta-analysis published in JACC. Franz Messerli and colleagues performed a systematic review of studies that compared HCTZ to other drugs using 24-hour ambulatory blood pressure monitoring and found that the decrease in blood pressure with HCTZ (6.5 mm Hg systolic and 4.5 mm Hg diastolic) was significantly less than with ACE inhibitors (12.9/7.7 mm Hg), ARBs (13.3/7.8 mm Hg), beta-blockers (11.2/8.5 mm Hg), and calcium channel blockers (11.0/8.1 mm Hg).

The authors note that HCTZ is as effective as the other antihypertensive agents when blood pressure is measured in the office. They write that this suggests that HCTZ is likely less effective at night. Although HCTZ is widely perceived to be clinically effective in improving outcomes, Messerli and colleagues write that “all outcome studies were done with higher doses than the currently used 12.5 to 25 mg or with other thiazides such as chlorthalidone or indapamide.”

However, because HCTZ is “suboptimal” as monotherapy, that “should not prevent it from being useful in combination with” other agents, since many studies have found that HCTZ in combination with other agents yields an incremental reduction in blood pressure.

7 Responses to “New Study Finds Hydrochlorothiazide Inferior To All Other BP Drugs”

  1. Lorenzo Marchini, MD says:

    The problem with the meta-analysis comparing HCTZ with ACE inhibitors, ARBs and beta-blockers is that a decrease of BP cannot be equated to a decrease of clinical events in pharmacological trials. Besides, the doses of 12.5 and 25 mg. are now generally used in combination therapy, and not in monotherapy, where higher doses have been effectively used with good clinical outcomes and without an excess of side effects.
    Furthermore, it’s useful to note that diuretics, with old generation bblockers are the less expensive drugs for hypertension and that’s not
    of little relevance given the worlwide problem of public health expenditure.

    Competing interests pertaining specifically to this post, comment, or both:

  2. Robin Motz, M.D., Ph.D. says:

    I agree with the above. Thiazide diuretic anti-hypertensive therapy has been shown to reduce the incidence of CVA’s. This should be the endpoint, rather than the degree of blood pressure lowering. In fact, has any other anti-hypertensive agent used as solo therapy ever been shown to reduce the incidence of CVA’s?

  3. peter sereny, MD says:

    All good points. It should also be noted that as our understanding of hypertension, specifically as it relates to volume/renin advances, we should be able to better classify individual patients as to what class of drug may be best for them. Instead of renewing HCTZ, I have been switching my patients to chlorthalidone.

    Competing interests pertaining specifically to this post, comment, or both:

  4. Most patients require combination therapy where low dose thiazide 12.5 mg is appropriate especially in older hypertensive pts. Monotherapy with thiazide 12.5 mg cannnot control BP over 24 hr period, that is clear. As for Peter Sereny, I would recommend regular check for serum potassium and magnesium when administering chlortalidone. This long-acting diuretic has better antihypertensive effect, yet much more profound diuretic effect. According to my experience, nearly all the pts taking chlortalidone (combined with atenolol in one tablet) had significant hypokalemia. Neither indapamide SR 1.25 mg is devoid of hypokalemic effect(see review in Drugs).

  5. Robin Motz, M.D., Ph.D. says:

    Then why not generic Dyazide? (I know, diabetics run a possible risk of kidney stones from the triamterene, but I have never seen it in 35 years of practice and ward attending.

  6. David Powell , md, facc says:

    The evidence base would favor chlorthalidone over HCTZ for stroke prevention. The risk of hypokalemia has not been statistically different, provided that the 2:1 hctz to chlor ratio is compared (and this is the BPcomparison as well). Also, BP control is better in combo therapy with ARB, as seen in a recent Takeda sponsered trial.

    Competing interests pertaining specifically to this post, comment, or both:

  7. David Powell made me look for the ratio 2:1 plus no difference in hypokalemia ( http://hyper.ahajournals.org/cgi/content/full/54/5/951 ).
    My personal experience came about with Tenoretic containing chlortaliodne 25 mg (that is equivalent to hydrocholorthiazide 50 mg) and this is the dose causing hypokalemia. No wonder that this proved to be true in my practice.
    The decrease 0.5 mEq/L in serum potassium with either drug in the reference paper does not seem big. Let us take the patients having potassium 3.8 mEq/L prior to starting either diuretic. On treatment their potassium decreases to 3.3 mEq/L. I do NOT like mild degrees of hypokalemia due to overall ion depletion.