Thomopoulos Costas, Parati Gianfranco, Zanchetti Alberto
aDepartment of Cardiology, Helena Venizelou Hospital, Athens, Greece bDepartment of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano IRCCS cDepartment of Medicine and Surgery, University of Milan Bicocca dScientific Direction, Istituto Auxologico Italiano IRCCS eCentro Interuniversitario di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Milan, Italy.
J Hypertens. 2016 Oct;34(10):1921-32. doi: 10.1097/HJH.0000000000001052.
Choice of antihypertensive drugs is also based on the expected burden of adverse events associated with each class of agents, and we have recently identified treatment discontinuation for adverse events as a measure of treatment tolerability frequently reported in randomized controlled trials (RCTs).
To investigate whether all classes of blood pressure (BP) lowering drugs increase discontinuations for adverse events when compared with placebo and whether risk of discontinuation is similar for all classes when compared in head-to-head RCTs.
RCTs of BP-lowering treatment were subdivided in groups according to class of drug compared with placebo or with other classes. Risk ratios and 95% confidence intervals of major cardiovascular events and of treatment discontinuations for adverse events were calculated (random-effects model).
Thirty-eight placebo-controlled RCTs (147 788 patients) and 37 head-to-head RCTs (242 481 patients) provided comparative information on discontinuations for adverse events. All classes of drugs significantly increased discontinuations for adverse events over those occurring on placebo: risk ratio diuretics 2.23 (1.32-3.76), beta-blockers 2.88 (1.58-5.28), calcium antagonists 2.03 (1.17-3.56), angiotensin-converting enzyme inhibitors 2.78 (1.37-5.47), central agents 1.74 (1.24-2.45), with the single exception of angiotensin receptor blockers, which did not significantly increase adverse events over placebo [risk ratio 1.13 (0.78-1.62)]. Similarly, in head-to-head comparison RCTs with other classes, angiotensin receptor blockers were the only class associated with a significantly lower risk of adverse events [risk ratio 0.71 (0.58-0.87)] when head-to-head compared with other classes. Regression analysis also shows that incidence of discontinuations for adverse events is proportional to the number of antihypertensive and other cardiovascular drugs, which accounts for the high incidence of this outcome often found in groups randomized to placebo.
Reduction of cardiovascular events by all classes of BP-lowering drugs is accompanied by increased treatment discontinuations for adverse events, except when angiotensin receptor blockers are used. Treatment discontinuations are also related to treatment often accompanying antihypertensive agents.
降压药物的选择还基于各类药物预期的不良事件负担，并且我们最近已将因不良事件导致的治疗中断确定为随机对照试验（RCT）中经常报告的治疗耐受性指标。
研究与安慰剂相比，各类降压药物是否会增加因不良事件导致的治疗中断，以及在直接比较的RCT中，各类药物的中断风险是否相似。
根据与安慰剂或其他类药物相比的药物类别，将降压治疗的RCT分为不同组。计算主要心血管事件和因不良事件导致的治疗中断的风险比及95%置信区间（随机效应模型）。
38项安慰剂对照的RCT（147788例患者）和37项直接比较的RCT（242481例患者）提供了因不良事件导致治疗中断的比较信息。与安慰剂相比，所有类别的药物因不良事件导致的治疗中断均显著增加：利尿剂的风险比为2.23（1.32 - 3.76），β受体阻滞剂为2.88（1.58 - 5.28），钙拮抗剂为2.03（1.17 - 3.56），血管紧张素转换酶抑制剂为2.78（1.37 - 5.47），中枢作用药物为1.74（1.24 - 2.45），唯一例外的是血管紧张素受体阻滞剂，与安慰剂相比，其并未显著增加不良事件[风险比1.13（0.78 - 1.62）]。同样，在与其他类别进行直接比较的RCT中，与其他类别相比，血管紧张素受体阻滞剂是唯一与不良事件风险显著较低相关的类别[风险比0.71（0.58 - 0.87）]。回归分析还表明，因不良事件导致的治疗中断发生率与抗高血压药物及其他心血管药物的数量成正比，这解释了在随机分配至安慰剂组中该结果的高发生率。
除使用血管紧张素受体阻滞剂外，各类降压药物在降低心血管事件的同时，因不良事件导致的治疗中断也会增加。治疗中断也与常伴随抗高血压药物的治疗有关。
