Gjesing Anne, Gislason Gunnar H, Christensen Stefan B, Jørgensen Mads E, Mérie Charlotte, Norgaard Mette Lykke, Poulsen Henrik Enghusen, Gustafsson Finn, Køber Lars, Torp-Pedersen Christian, Andersson Charlotte
Department of Cardiology, Copenhagen University Hospital Gentofte, Copenhagen, Denmark.
Pharmacoepidemiol Drug Saf. 2015 Mar;24(3):310-8. doi: 10.1002/pds.3746. Epub 2015 Feb 4.
Leg cramps are common in patients with heart failure. Quinine is frequently prescribed in low doses to these patients, but safety of this practice is unknown. We studied the outcomes associated with use of quinine in a nationwide cohort of patients with heart failure.
Through individual-level-linkage of Danish national registries, we identified patients discharged from first-time hospitalization for heart failure in 1997-2010. We estimated the risk of mortality associated with quinine treatment by time-dependent Poisson regression models.
A total of 135 529 patients were included, with 14 510 patients (11%) using quinine at some point. During a median time of follow-up of 989 days (interquartile range 350-2004) 88 878 patients (66%) died. Patients receiving quinine had slightly increased mortality risk, adjusted incidence rate ratio (IRR) 1.04 (95% confidence interval [CI] 1.01 to 1.07). The risks differed according to concomitant β-blocker treatment. For patients treated with both quinine and β-blockers IRR was 1.15 (95% CI 1.09 to 1.21) vs. 0.99 (95% CI 0.96 to 1.03) for patients treated with quinine but not β-blockers. The risks were highest shortly after initiation of therapy: for the first 14 days of treatment IRR was 2.12 (95% CI 1.54 to 2.93) for patients in treatment with β-blockers and 1.17 (95% CI 0.86 to 1.59) for patients not treated with β-blockers.
Use of quinine was common and associated with increased mortality in heart failure, especially if administered together with β-blockers and shortly after treatment initiation. Mechanisms underlying the findings remain to be established.
腿部痉挛在心力衰竭患者中很常见。低剂量奎宁经常被开给这些患者，但这种做法的安全性尚不清楚。我们在全国范围内的心力衰竭患者队列中研究了使用奎宁的相关结果。
通过丹麦国家登记处的个体层面关联，我们确定了1997 - 2010年因心力衰竭首次住院出院的患者。我们通过时间依赖性泊松回归模型估计了与奎宁治疗相关的死亡风险。
共纳入135529例患者，其中14510例患者（11%）在某个时间点使用过奎宁。在中位随访时间989天（四分位间距350 - 2004天）内，88878例患者（66%）死亡。接受奎宁治疗的患者死亡风险略有增加，调整后的发病率比（IRR）为1.04（95%置信区间[CI]1.01至1.07）。风险因同时使用β受体阻滞剂治疗而有所不同。同时接受奎宁和β受体阻滞剂治疗的患者IRR为1.15（95%CI 1.09至1.21），而仅接受奎宁治疗但未使用β受体阻滞剂的患者IRR为0.99（95%CI 0.96至1.03）。治疗开始后不久风险最高：在治疗的前14天，使用β受体阻滞剂的患者IRR为2.12（95%CI 1.54至2.93），未使用β受体阻滞剂的患者IRR为1.17（95%CI 0.86至1.59）。
奎宁的使用很常见，且与心力衰竭患者死亡率增加相关，尤其是与β受体阻滞剂同时使用以及治疗开始后不久使用时。这些发现背后的机制仍有待确定。
