Incidence Rates and HRs for MACEs

Cardiovascular Event Rates According to Cardiovascular Disorders at Baseline Risk factors recorded at baseline included the presence of hypertension, diabetes mellitus, hyperlipidemia, and a history of heart disease (Table 1). Adjudicated event rates were higher in patients with baseline cardiovascular risk factors than in those without baseline cardiovascular risk (Table 4). HRs for MACEs found in patients treated with roflumilast relative to placebo in patients without cardiovascular diseases or risk factors at baseline were lower than in those with cardiovascular comorbid conditions. Adjusting for cardiovascular risk factors at baseline did not materially affect the HR for MACEs. 

Rates and HRs for MACEs

There were significantly fewer MACEs for roflumilast than for placebo in the subgroup of patients with COPD who did not have cardiovascular comorbid conditions at baseline (Table 1). Cardiovascular Event Rates According to Other Factors at Baseline Adjudicated event rates according to age, sex, smoking status, COPD severity, and concomitant long-term pulmonary medication use are shown in Figure 3. HRs were similar across age, sex, and smoking status. There were no significant interactions for COPD severity, concomitant inhaled corticosteroid use, or long-acting b-agonist use. 

However, reductions in MACEs were significant in patients with severe COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage III), in those using concomitant inhaled corticosteroids, and in those not using long-acting Ь-agonists and not in the corresponding subgroups. Cardiovascular Event Rates According to COPD Exacerbations Subanalyses of the four trials carried out for 1 year demonstrated that exacerbations of COPD were reduced significantly by roflumilast relative to placebo. 

Between patients with and without exacerbations, the proportions with MACEs were similar (1.7% and 1.6%, respectively). Between patients with and without MACEs, the proportions experiencing exacerbations were similar (43.2% and 42.1%, respectively). Table 4—Incidence Rates and HRs for MACEs According to Baseline CV Comorbid Diseases

Patient Group	Roflumilast	Placebo	HR (Roflumilast vs Placebo)	95% CI	P Value
No. patients with CV comorbid conditions	3,584	3,056
Composite MACE	43 (1.2)	51 (1.7)	0.75	0.50-1.14	.185
CV death	27 (0.8)	31 (1.0)	0.72	0.43-1.23	.232
Nonfatal MI	10 (0.3)	12 (0.4)	0.94	0.40-2.20	.893
Nonfatal stroke	6 (0.2)	9 (0.3)	0.55	0.18-1.66	.288
No. patients without CV comorbid conditions	2,979	2,435
Composite MACE	9 (0.3)	25 (1.0)	0.36	0.17-0.77	.009
CV death	8 (0.3)	12 (0.5)	0.65	0.26-1.59	.340
Nonfatal MI	1 (0.0)	10 (0.4)	0.09	0.01-0.70	.021
Nonfatal stroke	0 (0.0)	3(0.1)	0		.996

Data are presented as No. (%), unless otherwise indicated. See Table 3 legend for expansion of abbreviations. “Calculated using Cox proportional hazard model with terms for treatment, age, sex, smoking status, and country pool. Includes ischemic heart disease, type 2 diabetes, dyslipidemia, and hypertension.