Pharmacological interventions for hypertensive emergencies

  • Review
  • Intervention

Authors

  • Marco I Perez,

    Corresponding author
    1. University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada
    • Marco I Perez, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Science Mall, Vancouver, BC, V6T 1Z3, Canada. marco.perez@ti.ubc.ca.

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  • Vijaya M Musini,

    1. University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada
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  • James M Wright

    1. University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, Vancouver, BC, Canada
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Abstract

Background

Hypertensive emergencies, marked hypertension associated with acute end-organ damage, are life-threatening conditions. Many anti-hypertensive drugs have been used in these clinical settings. The benefits and harms of such treatment and the best first-line treatment are not known.

Objectives

To answer the following two questions using randomized controlled trials (RCTs): 1) does anti-hypertensive drug therapy as compared to placebo or no treatment affect mortality and morbidity in patients presenting with a hypertensive emergency? 2) Does one first-line antihypertensive drug class as compared to another antihypertensive drug class affect mortality and morbidity in these patients?

Search methods

Electronic sources: MEDLINE, EMBASE, Cochrane clinical trial register. In addition, we searched for references in review articles and trials. We attempted to contact trialists. Most recent search August 2007.

Selection criteria

All unconfounded, truly randomized trials that compare an antihypertensive drug versus placebo, no treatment, or another antihypertensive drug from a different class in patients presenting with a hypertensive emergency.

Data collection and analysis

Quality of concealment allocation was scored. Data on randomized patients, total serious adverse events, all-cause mortality, non-fatal cardiovascular events, withdrawals due to adverse events, length of follow-up, blood pressure and heart rate were extracted independently and cross checked.

Main results

Fifteen randomized controlled trials (representing 869 patients) met the inclusion criteria. Two trials included a placebo arm. All studies (except one) were open-label trials. Seven drug classes were evaluated in those trials: nitrates (9 trials), ACE-inhibitors (7), diuretics (3), calcium channel blockers (6), alpha-1 adrenergic antagonists (4), direct vasodilators (2) and dopamine agonists (1).
Mortality event data were reported in 7 trials. No meta-analysis was performed for clinical outcomes, due to insufficient data. The pooled effect of 3 different anti-hypertensive drugs in one placebo-controlled trial showed a statistically significant greater reduction in both systolic [WMD -13, 95%CI -19,-7] and diastolic [WMD -8, 95%CI, -12,-3] blood pressure with antihypertensive therapy.

Authors' conclusions

There is no RCT evidence demonstrating that anti-hypertensive drugs reduce mortality or morbidity in patients with hypertensive emergencies. Furthermore, there is insufficient RCT evidence to determine which drug or drug class is most effective in reducing mortality and morbidity. There were some minor differences in the degree of blood pressure lowering when one class of antihypertensive drug is compared to another. However, the clinical significance is unknown. RCTs are needed to assess different drug classes to determine initial and longer term mortality and morbidity outcomes.

アブストラクト

高血圧緊急症に対する薬理学的介入

背景

高血圧緊急症は終末臓器の急性障害を伴う顕著な高血圧症であり、致死的な状態にある。これらの臨床診療現場では多くの降血薬が使用されてきた。このような治療の利益と有害性、ならびに最善の第一選択治療法はわかっていない。

目的

ランダム化比較試験(RCT)を用いて以下の2つの疑問に答えることを目的とした:1)降圧薬治療はプラセボまたは無治療と比較して、高血圧緊急症の患者の死亡率や罹患率に対して効果があるか、2)第一選択の降圧薬クラスは他のクラスの降圧薬と比較して、高血圧緊急症の患者の死亡率や罹患率に対して効果があるか。

検索戦略

電子的出典:MEDLINE、EMBASE、Cochrane clinical trial register。さらに、レビュー論文および試験の参照文献を検索した。試験実施者への問い合わせを試みた。最新検索2007年8月。

選択基準

高血圧緊急症の患者を対象に降圧薬をプラセボ、無治療または別のクラスの降圧薬と比較した交絡のない真のランダム化試験すべて。

データ収集と分析

割付けの隠蔽化の質をスコア化した。ランダム化した患者、すべての重篤な有害事象、全原因死亡率、非致死的な心血管イベント、有害事象による中止、追跡期間、血圧、心拍数に関するデータを独自に抽出し、クロスチェックした。

主な結果

15件のランダム化比較試験(患者869例)が選択基準に合致した。2件の試験ではプラセボ群が設定されていた。研究はすべて(1件を除いて)非盲検試験であった。これらの試験で以下の7つの医薬品クラスが評価されていた:硝酸塩(9件の試験)、ACE阻害薬(7件)、利尿薬(3件)、カルシウムチャネル遮断薬(6件)、α1-アドレナリン拮抗薬(4件)、直接血管拡張薬(2件)、ドーパミン作動薬(1件)である。7件の試験で死亡イベントのデータが報告されていた。データが不十分であったため、臨床アウトカムについてのメタアナリシスは行わなかった。1件のプラセボ比較試験で異なる降圧薬3剤をプールしたデータから、抗高血圧治療によって収縮期血圧[重み付け平均差(WMD)-13、95%CI -19~-7]および拡張期血圧[WMD -8、95%CI -12~-3]ともに統計学的に有意な著しい低下が示された。

著者の結論

降圧薬が高血圧緊急症の患者の死亡率または罹患率を低下させるとするRCTからのエビデンスはない。また、どの薬剤または医薬品クラスが死亡率および罹病率の低下に最も有効であるかを判定するためにも、RCTからのエビデンスは不十分である。あるクラスの降圧薬を別のクラスと比較した際に、血圧の下降程度にわずかな差があったが、その臨床的意義は不明である。初期および長期の死亡率および罹病率のアウトカムを判定するために、異なる医薬品クラスを評価するRCTが必要である。

訳注

監  訳: 曽根 正好,2008.4.1

実施組織: 厚生労働省委託事業によりMindsが実施した。

ご注意 : この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、Minds事務局までご連絡ください。Mindsでは最新版の日本語訳を掲載するよう努めておりますが、編集作業に伴うタイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

Pharmacological interventions for hypertensive emergencies

Hypertensive emergencies occur when high blood pressure is associated with the presence of acute end organ damage, such as heart attack or stroke. There is controversy as to when and which blood pressure drugs to use in these situations. This review looked for all studies where patients were randomized to one or more treatments to measure the effects of such therapies. The questions of the review were to see whether drug treatments affected death or cardiovascular morbidity or whether there were differences between drug treatments. The available evidence was insufficient to answer these questions.

Laički sažetak

Lijekovi za liječenje hitnih hipertenzivnih stanja

Hitna hipertenzivna stanja javljaju se kad je visoki arterijski krvni tlak povezan s postojanjem naglog krajnjeg oštećenja organa kao što je srčani ili moždani udar. Nije jasno kada i koje lijekove protiv visokog krvnog tlaka u tim stanjima treba koristiti. Ovaj Cochrane sustavni pregled ispitao je sve kliničke studije u kojima su pacijenti razvrstani u skupine koje su primale jednu ili više terapija kako bi se ispitali učinci tih terapija. Cilj ovog Cochrane sustavnog preglda bio je ispitati da li lijekovi protiv visokog tlaka mogu utjecati na smrt ili srčano-žilnu bolest i postoje li razlike između različitih lijekova. Dostupni dokazi nisu bili dovoljni da bi se odgovorilo na ta pitanja.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Livia Puljak
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr