1. Early BP Screening and Treatment Absolutely Necessary

    In their Clinical Guideline article Drs. Wolff and Miller concluded that, while there was no new evidence on the benefits of screening for high blood pressure (BP), there was new evidence on the harms of treatment of early hypertension in that “pharmacologic therapy is associated with common side effects”(1). We take issue with this statement and submit that their conclusions stem from a highly selective, if not to say biased, interpretation of the literature. When discussing the TROPHY study (2), Drs. Wolff and Miller extensively list all the adverse events with a (non significantly) higher rate with candesartan than with placebo. However, they conveniently forget to list the adverse events that occurred at a (non significantly) higher rate with placebo than with candesartan. Thus, arthralgia, back pain, sinusitis, bronchitis, depression, nausea and angioedema were more common in the placebo group than in the candesartan group. Overall, candesartan was as well or even better tolerated than placebo in this study as is documented by the fact that there were 14 (3.5%) patients in the candesartan group who had a serious adverse event as opposed to 23 (5.9%) in the placebo group. Regardless of whether the incidence of adverse events is 5% or 50% it should not be quantified as more or less “common” as long as it does not significantly differ from placebo.

    Hypertension by and large is an asymptomatic disease and should remain so while under therapy. Apart from nuisance side effects such as pedal edema with calcium antagonists and cough with ACE inhibitors, modern antihypertensive therapy is exceedingly well-tolerated and adverse events are, in general, not distinguishable from placebo. A meta-analysis of 94 randomized placebo-controlled trials (17,641 participants) of 4 different classes of blood pressure–lowering drugs (thiazides, ß-blockers, ACE inhibitors, and angiotensin II receptor antagonists) showed that the prevalence of headache was reduced (P<0.001) with each of the 4 drug strategies(3). Similarly, in a meta-analysis of 7 randomized, double- blind, placebo-controlled trials with more than 2000 patients, the use of an angiotensin receptor blocker was associated with a significant reduction in the incidence of headache (p=0.003) when compared to placebo(4). These data suggest that the incidence of headaches occurring with untreated hypertension can be reduced by antihypertensive therapy. Moreover, the Hypertension Optimal Treatment (HOT) Study (5) found that intensive BP lowering was associated with improved quality of life. Despite the aggressive use of antihypertensive agents, a substudy of patients participating in the HOT Study (n=610) demonstrated that intensive BP lowering improved quality of life and 2 self-administered questionnaires—the Psychological General Well-Being Index and the Subjective Symptoms Assessment Profile—indicated that the lower the diastolic BP achieved, the greater the improvement in well-being reported by patients(6). It is studies like these that deserve to be emphasized, given that in the United States still about two-thirds of patients with hypertension do not have their BP under control. By indiscriminately disparaging antihypertensive therapy as being fraught with side effects, Drs. Wolff and Miller have provided a disservice to patients and physicians alike.

    Franz H. Messerli, MD, Kelly C. Hanretta, DO, Division of Cardiology St.Luke's-Roosevelt Hospital Columbia University College of Physicians and Surgeons 1000 Tenth Avenue New York, NY 10019

    References

    1. Wolff T, Miller T. Evidence for the reaffirmation of the U.S. Preventive Services Task Force recommendation on screening for high blood pressure. Ann Intern Med 2007;147:787-91.

    2. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, Black HR, Grimm RH Jr, Messerli FH, Oparil S, Schork MA; Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med. 2006 Apr 20;354(16):1685-97.

    3. Law M, Morris JK, Jordan R, Wald N. Headaches and the treatment of blood pressure: results from a meta-analysis of 94 randomized placebo- controlled trials with 24,000 participants. Circulation. 2005 Oct 11;112(15):2301-6.

    4. Hansson L, Smith DH, Reeves R, Lapuerta P. Headache in mild-to- moderate hypertension and its reduction by irbesartan therapy. Arch Intern Med. 2000 Jun 12;160(11):1654-8.

    5. Wiklund I, Halling K, Rydén-Bergsten T, Fletcher A. Does lowering the blood pressure improve the mood? Quality-of-life results from the Hypertension Optimal Treatment (HOT) study. Blood Press. 1997 Nov;6(6):357 -64.

    6. Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, Ménard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. 1998 Jun 13;351(9118):1755-62.

    Conflict of Interest:

    Dr. Messerli is ad hoc consultant/speaker for the following organizations: GSK, Novartis, Pfizer, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Forest, Daiichi Sankyo, Sanofi, Merck, Jerini, King Pharmaceuticals and Mars.

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