Previous studies have related severity of airflow limitation to cardiovascular disease. We evaluated whether this relationship could be observed from a single large prospective trial.
Evaluation of adverse events during the UPLIFT trial (4-yr randomized, double-blind, placebo-controlled trial of tiotropium in patients with COPD). Adverse events incidence rates were determined from the total number of patients with an event divided by total time at risk. Rate ratios (RR) and 95% CI for TIO/PBO were calculated. A composite CV endpoint was defined to include CV deaths + non-fatal myocardial infarction (MI) + non-fatal stroke + sudden death + sudden cardiac death + cardiac death.
5,895 patients were included in the analysis including 46% GOLD Stage II, 45% Stage III and 9% Stage IV. % men according to stage: 72, 76, 78; mean age according to stage: 64, 65, 62 yrs. Incidence rates (per 100 pt-years) for selected CV events for TIOvsPBO according to stage: cardiac (total) 5.59vs6.21, 7.29vs8.28, 8.65vs10.8 (ischemic heart dis. 2.43vs2.63, 2.19vs2.65, 2.15vs1.83; atrial fib/flutter 0.86vs1.15, 1.68vs1.53, 1.50vs1.31; cardiac failure 1.22vs1.82, 2.34vs2.72, 3.66vs4.24; MI 0.72vs0.91, 0.67vs1.07, 0.90vs1.16); vascular (total) 5.15vs5.98, 6.35vs5.94, 5.30vs5.41 (hypertension 2.89vs3.75, 3.51vs3.40, 2.96vs3.41), stroke (total) 0.80vs0.96, 0.97vs0.85, 0.74vs0.99; CV endpoint 1.99vs2.67, 2.70vs3.56, 3.93vs4.72. RR (95%CI) of TIO/PBO for the composite CV endpoint according to stage were 0.74(0.56,0.98), 0.76(0.59,0.98), 0.83(0.49,1.42).
Reporting of adverse events during a 4-yr trial indicated an increased risk of CV events according to GOLD stage, although variability is observed among different categories of disease. Potential confounding factors include age, smoking history, and variability due to small numbers. Tiotropium reduces the risk of a CV event irregardless of GOLD stage.
Clinical trial data support an association of CV disease with GOLD stage. Funded by: Boehringer Ingelheim and Pfizer.
Donald Tashkin, No Financial Disclosure Information; No Product/Research Disclosure Information