Fontana Marianna, Asaria Perviz, Moraldo Michela, Finegold Judith, Hassanally Khalil, Manisty Charlotte H, Francis Darrel P
International Centre for Circulatory Health, National Heart and lung Institute, Imperial College London, UK.
Circulation. 2014 Jun 17;129(24):2539-2546. doi: 10.1161/CIRCULATIONAHA.113.007595. Epub 2014 Apr 17.
Primary prevention guidelines focus on risk, often assuming negligible aversion to medication, yet most patients discontinue primary prevention statins within 3 years. We quantify real-world distribution of medication disutility and separately calculate the average utilities for a range of risk strata.
We randomly sampled 360 members of the general public in London. Medication aversion was quantified as the gain in lifespan required by each individual to offset the inconvenience (disutility) of taking an idealized daily preventative tablet. In parallel, we constructed tables of expected gain in lifespan (utility) from initiating statin therapy for each age group, sex, and cardiovascular risk profile in the population. This allowed comparison of the widths of the distributions of medication disutility and of group-average expectation of longevity gain. Observed medication disutility ranged from 1 day to >10 years of life being required by subjects (median, 6 months; interquartile range, 1-36 months) to make daily preventative therapy worthwhile. Average expected longevity benefit from statins at ages ≥50 years ranges from 3.6 months (low-risk women) to 24.3 months (high-risk men).
We can no longer assume that medication disutility is almost zero. Over one-quarter of subjects had disutility exceeding the group-average longevity gain from statins expected even for the highest-risk (ie, highest-gain) group. Future primary prevention studies might explore medication disutility in larger populations. Patients may differ more in disutility than in prospectively definable utility (which provides only group-average estimates). Consultations could be enriched by assessing disutility and exploring its reasons.
一级预防指南关注风险，通常假定对药物治疗的厌恶可忽略不计，但大多数患者在3年内停用一级预防他汀类药物。我们对药物负效用的实际分布进行量化，并分别计算一系列风险分层的平均效用。
我们在伦敦随机抽取了360名普通公众。药物厌恶被量化为每个人为抵消服用理想化每日预防性药片的不便（负效用）所需的寿命延长。同时，我们构建了针对人群中每个年龄组、性别和心血管风险状况开始他汀类药物治疗后预期寿命延长（效用）的表格。这使得能够比较药物负效用分布的宽度与群体平均预期寿命延长情况。观察到的药物负效用范围为受试者需要1天到超过10年的寿命（中位数为6个月；四分位间距为1 - 36个月）才能使每日预防性治疗变得值得。年龄≥50岁的人群中，他汀类药物预期的平均寿命获益范围为3.6个月（低风险女性）至24.3个月（高风险男性）。
我们不能再假定药物负效用几乎为零。超过四分之一的受试者的负效用超过了即使是最高风险（即获益最大）组预期的他汀类药物群体平均寿命获益。未来的一级预防研究可能会在更大规模人群中探索药物负效用。患者在负效用方面的差异可能比在前瞻性可定义的效用方面（后者仅提供群体平均估计）更大。通过评估负效用并探究其原因，可丰富咨询内容。
