干预可提高急性冠脉综合征后药物治疗依从性但不能改善结局

在11月17日召开的美国心脏学会(AHA)年会上，来自丹佛退伍军人管理局医疗中心的P. Michael Ho博士报告称，一项前瞻性临床随机试验表明，在因急性冠脉综合征(ACS)住院的患者中，多方面干预可有效提高出院后药物治疗的依从性，但对血压和胆固醇水平的达标情况无明显影响。

Ho博士指出，有研究表明在因ACS住院的患者中，出院后患者对心脏保护药物治疗方案的依从性往往较差。例如，几项研究显示在出院时接受心脏药物治疗的患者中，1个月后大约1/3停用了至少一种药物，1年后只有大约60%的患者仍在坚持服用他汀类药物。队列研究和基于人群的研究表明，急性心肌梗死(MI)后对心脏保护药物治疗方案的依从性差与1年和长期死亡率增加相关。

在这项试验中，患者因ACS在位于丹佛、西雅图、北卡罗来纳州达勒姆或阿肯色州小石城的退伍军人管理局医疗中心接受住院治疗，并于2010或2011年出院。这些患者在出院前被随机分配至干预组(122例)或常规照护组(119例)。

干预措施在出院后持续1年，具体包括以下几个方面：

· 药物整合和调整，由药剂师通过亲自诊所访视或电话与患者沟通。药剂师负责解决用药问题或不良反应，整合用药差异，必要时提供药盒和使用说明，一个月后电话随访，同时提醒处方再配日期，回答患者的疑问并且鼓励患者依从治疗。

· 患者教育，于出院时以及之后由药剂师在1周和1个月随访时进行。在此之后，通过自动语音信息以及药剂师的电话提供教育信息。

· 合作照护，包括药剂师与初级保健医师或心脏科医师之间的沟通。

· 根据事先安排好的间隔时间，定期发送语音信息以提供患者用药和再配处方。

结果显示，包括以药剂师为主导的药物整合和调整、患者教育、药剂师与医生之间的合作以及语音信息提醒等的干预措施使干预组的药物治疗依从率达到了89.3%，而常规照护组的依从率只有73.9%。

此外，干预组的平均PDC显著高于常规照护组(0.94比0.87天)；干预组依从氯吡格雷(86.8%比70.7%)、他汀类药物(93.2%比71.3%)以及ACE抑制剂和血管紧张素受体阻滞剂 (93.1%比81.7%)的患者比例也更高。两组患者在β受体阻滞剂的使用情况方面无显著差异(88.1%比84.8%)。

Ho博士报告称，虽然治疗依从性有所改善，但两组在达到血压控制目标或LDL胆固醇控制目标的患者比例方面无显著差异，只是干预组较之常规照护组呈现出血压控制率更高(58.6%比48.9%)、收缩压降幅更大(–12 比 –4 mm Hg)以及舒张压降幅更大(–5比–3 mm Hg)的趋势。

Ho博士在论文中写道，此外，依从治疗的患者接受LDL胆固醇实验室随访评估的几率更高，“我们观察到干预组和常规照护组患者的LCL-C水平均有所下降，这可能减弱了干预措施对LDL-C水平的影响。”他指出，还需要进一步开展样本量更大的研究以评估依从性与这些临床结局之间的相关性。

基于药剂师花费的时间、心脏科医师花费的时间以及药盒的成本，这种干预措施的成本大约为每名患者360美元。干预组与常规照护组在药物治疗成本方面无显著差异。

Ho博士总结道，在这项试验中，干预措施使依从治疗的患者比例提高了大约15%，对4类药物的平均依从性加起来提高了大约7%。他指出，上述结果加上既往干预研究的结果“为我们提供了越来越充分的证据基础，表明ACS患者出院后干预措施能改善患者对心脏药物治疗方案的依从性。”

他写道：“我们有必要继续长时间地随访患者以评估干预组的依从性更高是否意味着临床结局更好。”Ho博士表示，他和他的同事计划在初始12个月之后继续随访患者以评估结局和成本方面的长期差异。

这项研究也存在一些局限性，包括试验实施地退伍军人医疗中心以男性患者人群为主，以及采用的是药房处方再配数据而非药片计数来评估依从性。

上述研究结果同步发表于《JAMA 内科学》杂志上(JAMA Intern Med Nov.18 [doi:10.1001/jamainternmed.2013.12944])。

这项研究由美国退伍军人卫生管理局卫生服务研究&发展研究者经费资助。作者声明无相关利益冲突。

随刊述评：昂贵的干预措施收效不大

Rita F. Redberg博士在编者按中称这项研究“有趣且仔细”，她指出研究结果表明患者对他汀类药物、ACE抑制剂和血管紧张素受体阻滞剂的依从性绝对增加了11%，对β受体阻滞剂的依从性绝对增加了3%。

她指出，每名患者360美元的成本估计是基于“退伍军人系统相对较低的服务成本”，但是如果推广到美国每一名急性冠脉综合征患者身上(根据最新预测，每年大约250万名患者)，这种干预措施的成本将给医疗卫生成本每年增加10亿美元之多。

她写道：“出于多方面的原因，受试者中已经比较高的药物治疗依从率只是适度增加，即便这种效应维持3~5年甚至更长，可能也无法改善临床结局。当然，我们希望它能够改善。但是在建议投入这一策略之前，应先慎重了解患者结局是否真的能够改善。”

Redberg博士来自美国加州大学旧金山分校医学院和女性心血管服务中心，她是《JAMA内科学》的编辑。

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By: SHARON WORCESTER, Cardiology News Digital Network

A multifaceted intervention was effective for improving postdischarge medication adherence among patients hospitalized for acute coronary syndrome but had no effect on achievement of blood pressure and cholesterol level goals, in a prospective randomized clinical trial.

The intervention, which involved pharmacist-led medication reconciliation and tailoring, patient education, collaboration between pharmacists and physicians, and voice messaging reminders, was associated with an 89.3% medication adherence rate among 122 patients randomized to the intervention groups, compared with a 73.9% adherence rate among 119 patients randomized to receive usual care, Dr. P. Michael Ho of the Denver Veterans Administration Medical Center, reported on Nov. 17 at the American Heart Association scientific sessions.

The mean proportion of days covered was significantly higher in the intervention group than in the usual care group (0.94 vs. 0.87 days), and a greater proportion of patients in the intervention group were adherent to clopidogrel (86.8% vs. 70.7%), statins (93.2% vs. 71.3%), and ACE inhibitors and angiotensin receptor blockers (93.1% vs. 81.7%). No significant difference was seen between the groups with respect to use of beta-blockers (88.1% vs. 84.8%), Dr. Ho reported. The findings were published simultaneously with the presentation (JAMA Intern Med Nov.18 [doi:10.1001/jamainternmed.2013.12944]).

Despite the improved adherence to treatment, no differences were seen in the percentage of patients achieving blood pressure goals or LDL cholesterol goals, although there was a trend toward greater blood pressure control (58.6% vs. 48.9%), decline in systolic blood pressure (–12 vs. –4 mm Hg), and decline in diastolic blood pressure (–5 vs. –3 mm Hg) for intervention vs. usual care patients, respectively, he said.

Also, adherent patient were more likely to get follow-up LDL cholesterol laboratory evaluations, and "accordingly we saw declines in LDL-C levels in both intervention and usual care patients, which may have attenuated the intervention effect on LDL-C levels," he wrote in the JAMA article, noting that additional studies in larger patient samples are needed to assess the association between adherence and these clinical outcomes.

The cost of the intervention, based on the pharmacist time spent, cardiologist time spent, and pill box cost, was about $360/patient. Medication cost differences did not differ significantly between the intervention and usual care groups.

Patients in the study had been hospitalized for acute coronary syndrome at Department of Veterans Affairs Medical Centers in Denver, Seattle, Durham, N.C., or Little Rock, Ark., and were discharged during 2010 or 2011. They were randomized to the intervention or usual care group prior to discharge.

The intervention, which lasted 1 year following discharge, involved:

· Medication reconciliation and tailoring by a pharmacist who met with patients via an in-person clinic visit or by telephone. The pharmacist addressed medication problems or adverse effects, reconciled differences in medications, provided a pill box and instructions for use if needed, and called a month later to follow up, synchronize refill dates, answer questions, and encourage adherence.

· Patient education at the point of discharge, and afterward by the pharmacist at 1-week and 1-month visits. Thereafter, educational messages were provided via automated voice messages and pharmacist phone calls.

· Collaborative care involving pharmacist and primary care clinician or cardiologist communications.

· Voice messaging at regularly scheduled intervals to remind patients about medications and refills.

Studies show that postdischarge adherence to cardioprotective drug regimens is often poor among patients hospitalized for acute coronary syndrome. For example, several studies have shown that a third of those who were taking their cardiac medications at discharge discontinued at least one medication by 1 month, and only about 60% were still taking statin medications at 1 year. Cohort and population-based studies show that lower adherence to cardioprotective drug regimens after acute MI are associated with a higher 1-year and long-term mortality, Dr. Ho noted.

In the current study, the intervention improved the proportion of adherent patients by about 15% and the mean adherence to the four medications combined by about 7%, Dr. Ho said, noting that the findings, along with those from prior intervention studies, "provide an increasing evidence base of interventions to improve adherence to cardiac medication regimens after ACS discharge."

"It will be important for us to continue to follow up patients longer to assess whether the higher adherence in the intervention group translates into improved clinical outcomes," he wrote, noting that he and his colleagues plan to follow the patients beyond the initial 12 months to assess for differences in outcomes and costs in the longer term.

This study is limited by a number of factors, including the largely male patient population at the VA medical centers where it was conducted, and the use of pharmacy refill data rather than pill counts to assess adherence.

This study was funded by Veterans Health Administration Health Service Research & Development Investigator-Initiated Awards. The authors reported having no disclosures.

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Costly intervention showed no benefit

In an editor’s note, Dr. Rita F. Redberg called the work "interesting and careful," and noted that the findings demonstrate an absolute increase of 11% in adherence to statins, ACE inhibitors, and angiotensin receptor blockers, and a 3% increase in adherence to beta-blockers.

The cost estimate of $360/patient is based on the "relatively lower costs of services in the VA system," but if applied to every patient with acute coronary syndrome in the United States (about 2.5 million annually, by recent estimates), the costs of such an intervention would add $1 billion annually to health care costs, she noted.

"For many reasons, the relatively modest increases in already high rates of medication regimen adherence in the patients studied may not translate into improved outcomes even if maintained for 3-5 years or longer. Of course, we hope that they do. But before recommending investment in this strategy, it would be prudent to know that patient outcomes will actually improve," she wrote.

Dr. Redberg of the department of medicine and women’s cardiovascular services at the University of California, San Francisco, is editor of JAMA Internal Medicine.