心臟衰竭及合併慢性阻塞性肺疾病人使用乙型交感神經阻斷劑之效果評估

Evaluating the effectiveness of β-adrenoceptor blockers in heart failure with or without chronic obstructive pulmonary disease patients

林典佑(Tien-Tu Lin)

指導教授 ： 黃耀斌

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2016年)

摘要

研究背景：
根據美國及歐洲的治療指引，使用乙型交感神經阻斷劑 (β-blocker)可以增進心臟衰竭病人的預後及降低死亡率。然而在眾多的β-blockers中，並無足夠文獻證明是否任一的β-blockers優於另一者。而慢性阻塞性肺疾病是除了心臟相關共病症外，另一個常見的共病症。有許多的觀察性研究證明在合併有心臟衰竭及慢性阻塞性肺疾病之病人使用β-blockers仍是可以增進病人的存活，但是否β-blockers的選擇性對於臨床效益有影響仍是不明確。
目的：
本研究目的為評估不同的β-blockers對於心臟衰竭病人及心臟衰竭病合併慢性阻塞性肺疾病病人之療效差異。
研究方法：
本研究使用國家衛生研究院提供之健保資料庫做為資料來源。本研究分為兩部分。第一部分納入條件為有心臟衰竭病人。第二部分納入條件為心臟衰竭合併慢性阻塞性肺疾病之病人。將β-blockers分為兩組，low-dose為低於起始劑量，high-dose為高於起始劑量。利用Time-dependent Cox proportional hazards regression model評估不同β-blockers療效之差異。
研究結果與討論：
本研究結果分為兩大部分。第一部分共納入14875位心臟衰竭病人，利用propensity-score配對後，使用β-blockers及未使用β-blockers皆為5688人。在校正相關變相後，high-dose carvedilol 及high-dose bisoprolol皆能顯著將低死亡及降低因急性心臟衰竭住院的風險。而與high-dose carvedilol比較，在死亡及住院的風險，high-dose bisoprolol皆沒有統計顯著差異(死亡: adjusted hazard ratio (aHR)=1.18, 95% confidence interval (CI)=0.88-1.58; 住院: aHR=0.94, 95% CI=0.65-1.34)。
第二部分共納入1820人為合併心臟衰竭及慢性阻塞性肺疾病，在propensity-score配對後，使用β-blockers及未使用β-blockers皆為577人。在校正相關變相後，只有high-dose bisoprolol顯著降低死亡風險及些微降低因心臟衰竭住院風險(死亡: aHR=0.51, 95% CI=0.29-0.89; 住院: aHR=0.47, 95% CI=0.23-0.98)，而任一β-blocker皆與慢性阻塞肺疾病惡化沒有相關性。然而在加入non-evidence based β-blockers後，發現high-dose carvedilol也可顯著降低死亡(aHR=0.37, 95% CI=0.15-0.91)。
結論：
本研究發現carvedilol及bisoprolol能顯著降低心臟衰竭病人的死亡及心臟衰竭惡化住院的風險，而兩者間並沒有差異。而在同時患有慢性阻塞性肺疾病人，carvedilol及bisoprolol可顯著降低死亡。

關鍵字

心臟衰竭 ； 慢性阻塞性肺疾病 ； 乙型阻斷劑 ； 死亡 ； 急性惡化

並列摘要

Background:
According to guidelines and pivotal trials, β-blockers use is associated with better survival. However, the superiority of any two of β-blockers is still unclear. Among heart failure (HF) patients, chronic obstructive pulmonary disease (COPD) is one of common comorbidities. A number of observational studies had demonstrated that β-blockers was safe and even could improve survival in patients with HF and COPD, but whether the selectivity of β-blockers would cause impact on clinical outcome was still lack of evidence.
Aim of study:
The objective of this study was to compare the clinical outcome of different β-blockers in HF patient and in patient coexisting HF and COPD.
Methods:
We used National Health Insurance Research Database in Taiwan to implement a retrospective cohort study. The study was divided into two part. In the first part, we enrolled patients diagnosed HF. In the second part, we included those who coexisting HF and COPD. We divided β-blockers into two groups. Low-dose was lower than starting dose and high-dose was higher than starting dose. Time-dependent Cox proportional hazards regression model was applied to evaluate the effectiveness of β-blockers in these two population.
Results and discussion:
A total of 14875 were newly diagnosed HF patients during study period. After propensity-score matching, there were both 5688 patients in β-blocker users and nonusers. Among these population, we found high-dose carvedilol and high-dose bisoprolol significantly reduced the risk of death and hospitalization for HF while metoprolol didn’t. Compared with high-dose carvedilol, survival and hospitalization were not significantly different between carvedilol and bisoprolol (Death: adjusted hazard ratio (aHR)=1.18, 95% confidence interval (CI)=0.88-1.58; hospitalization for HF: aHR=0.94, 95% CI=0.65-1.34)
In the second part of this study, we identified 1872 patients concurrent HF and COPD. After matching, there were both 577 patients in β-blocker users and nonusers. Only high-dose bisoprolol significantly reduced the risk of death and slightly decreased hospitalization for HF (Dearth: aHR=0.51, 95% CI=0.29-0.89; hospitalization for HF: aHR=0.47, 95% CI=0.23-0.98). Thus, we did not found association between β-blockers use and COPD exacerbation. However, after adding non-evidence based β-blockers, high-dose carvedilol significantly reduced the risk of death (aHR=0.37, 95% CI=0.15-0.91).
Conclusion:
Carvedilol and bisoprolol were associated with better outcome in HF patient and no difference between two β-blockers. In concurrent HF and COPD patients, both carvedilol and bisoprolol had survival benefit.

並列關鍵字

Heart failure ； chronic obstructive pulmonary disease ； β-blockers ； death ； acute exacerbation

參考文獻

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