Methods

This study was approved by the Institutional Research Ethics Board at Sunnybrook Health Sciences Center at the University of Toronto.

Ontario is Canada’s largest province and has >13 million residents, all of whom have universal access to physician and hospital services through a single-payer, publicly funded health care program, administered by the Ministry of Health and Long Term Care of Ontario. Our analyses were conducted using data from the Cardiac Care Network (CCN) of Ontario. CCN is a network of the 18 member hospitals providing invasive cardiac procedures in Ontario. CCN maintains a prospective clinical registry of all subjects who undergo coronary angiography, PCI, or CABG in the province. This registry contains detailed demographic, clinical, and procedural data, the accuracy of which has been validated through selected chart audits and angiographic core laboratory validation.

Data from the CCN registry were linked to population-based administrative databases containing information on all Ontario residents. These databases are available at the Institute for Clinical Evaluative Sciences and were linked using encrypted unique patient identifiers. In our analyses, we used the Canadian Institute for Health Information Discharge Abstract Database, which contains data on all hospitalizations and the National Ambulatory Care Reporting Service database, which contains data for emergency department visits. Death was ascertained using the Ontario Registered Persons Database. Data on physician visits and consultations (hospital based and community based) were obtained from the fee-for-service claims history in the Ontario Health Insurance Program physician claims database. Medication data were obtained from the Ontario Drug Benefit (ODB) database, which has comprehensive drug utilization information on patients >65 years, for whom full drug coverage is provided for by the Ministry of Health and Long Term Care of Ontario.

Our cohort consisted of patients with an index angiogram for stable CHD from October 1, 2008, to September 30, 2011. The patients had at least 1 hemodynamically significant lesion, defined as a coronary stenosis of >70% in severity (or >50% in the left main artery). We restricted our cohort to patients >66 years at the time of angiography, to allow for an adequate 1-year look-back window to access pre-angiography medication use. Patients who underwent urgent angiography for myocardial infarction (MI) or acute coronary syndrome were excluded as were those who were being investigated for structural or valvular heart disease. We also excluded patients with a hospitalization for MI or acute coronary syndrome in the 90 days before the index angiogram to identify a stable cohort. Patients with multiple angiograms in the accrual time period were categorized based on their first angiogram.

The main exposure of interest was OMT within 12 months of the index angiogram. We defined OMT as the concurrent prescription of medications from all the following classes: β blocker, ACE inhibitor/ARB, and statin. There is no universally accepted definition of OMT. We selected our definition of OMT based on the strong recommendation for these 3 medication classes in the 2012 AHA/ACC stable CHD guidelines. We did not include acetylsalicylic acid (ASA) in the OMT definition as it is available over the counter and, therefore, is not accurately recorded in the ODB database. We did not report on clopidogrel and newer antiplatelet agents, given the absence of benefit in patients with stable CHD who are not revascularized. We assumed that once a patient received prescription for all 3 classes of medication, he/she was categorized in OMT group for the remainder of the study period. We were also interested in the relation between being on OMT and revascularization after index angiography. We defined revascularization as PCI or CABG within 90 days of the index angiogram. This definition is similar to that used previously in the literature and is accurate given wait-times for elective coronary revascularization in Ontario.

Over the period of follow-up, patients could transition from no OMT to OMT and from no revascularization to being revascularized. To incorporate this time-varying nature of our exposures, we defined 4 mutually exclusive exposure groups: (1) no OMT and not revascularized, (2) no OMT and revascularized, (3) OMT and not revascularized, and (4) OMT and revascularized.

Our primary outcome was all-cause mortality, and our secondary outcome was hospitalization for nonfatal MI. Follow-up was until March 31, 2012.

Multivariable hierarchical logistic models were used to identify predictors of OMT in the 12 months after angiography. These models incorporated hospital-specific random effects to account for the clustering of patients in the hospitals at which the angiogram was performed. To understand the impact of OMT on clinical outcomes, multivariable Cox proportional hazard models were developed. We used robust “sandwich-type” variance estimators to account for potential homogeneity in outcomes because of the clustering of patients within the hospitals at which the index angiogram was performed. Both OMT and revascularization were treated as time-varying covariates. All patients were initially considered as nonrevascularized and either OMT or non-OMT based on medications at the time of the index angiogram. When a patient underwent revascularization or began OMT based on the ODB record, the patient transitioned to the appropriate category. This approach captures the transition of patients from 1 exposure group to another and mitigates the potential for immortal time/survivorship bias. SAS, version 9.3 (SAS Institute Inc, Cary, North Carolina) was used for all analyses; p values of <0.05 were significant.

Results

There were a total of 183,630 angiograms performed from October 1, 2008, to September 30, 2011, to investigate suspected stable CHD ( Figure 1 ). Our final cohort consisted of 20,663 patients, of whom 12,614 (61%) were on OMT at 1-year post-angiogram. The initial treatment strategy was medical therapy for 8,630 patients and revascularization for 12,033 patients (7,537 with PCI and 4,496 with CABG).

Study population.

The baseline characteristics of the final cohort are listed in Table 1 . There were considerable differences between the patients who received OMT versus no OMT. Patients receiving OMT at 12 months were more likely to be younger and have higher rates of traditional cardiovascular risk factors.

At the time of the index angiogram, 37.8% of the overall cohort was on OMT. For a period of 12 months, this improved to 61.0% of the cohort ( Table 2 ). The overall rates of OMT in the medical therapy and revascularization groups were similar at 12 months. However, when examined for each class of medication, β blocker and statin use were statistically higher in the revascularized group, whereas ACE inhibitor/ARB use was statistically higher in the nonrevascularized group. Additional anti-ischemic medications including calcium channel blocker and nitrate use were significantly higher in the nonrevascularized group at 12-month post-angiogram. The low rate of antiplatelet use at baseline and a significance difference after angiogram is because of that the provincial drug database does not capture the use of over-the-counter antiplatelet drugs (i.e., ASA), and therefore, only clopidogrel and newer antiplatelet agents are accounted for.

Table 3 lists the results of the multivariable hierarchical logistic model to identify the predictors of OMT at 12-month post-angiogram. The strongest predictors were being on OMT at baseline and CABG after angiogram. PCI as the initial treatment strategy was not a statistically significant predictor of being on OMT. The factors that reduced the likelihood of receiving OMT at 12 months were older age and presence of COPD. Specialty of the referring physician for angiography (cardiologist vs others) and hospital-level factors including coronary angiogram volume or ability to perform PCI and/or CABG were not associated with being on OMT.

Table 3

Multilevel analysis: factors associated with receiving optimal medical therapy

Covariate	OR (95% CI)	p-value
Treatment
Non-revascularized	Referent
Coronary Artery Bypass Grafting	1.70 (1.53-1.89)	<0.001
Percutaneous Coronary Intervention	0.99 (0.92-1.08)	0.879
Optimal Medical Therapy At Baseline	14.40 (13.17-15.75)	<0.001
Demographics
Age	0.98 (0.98-0.99)	<0.001
Male	0.94 (0.87-1.02)	0.125
Rural	1.07 (0.97-1.18)	0.182
Income
5	Referent
1	1.05 (0.94-1.17)	0.364
2	0.98 (0.88-1.09)	0.678
3	1.01 (0.91-1.12)	0.855
4	1.03 (0.93-1.14)	0.587
Medical Comorbidities
Peripheral Vascular Disease	1.07 (0.96-1.19)	0.223
Previous Myocardial Infarction	1.11 (1.02-1.21)	0.011
Chronic Obstructive Pulmonary Disease	0.68 (0.60-0.77)	<0.001
Diabetes Mellitus	1.28 (1.19-1.38)	<0.001
Hypertension	1.55 (1.38-1.75)	<0.001
Smoking	0.99 (0.92-1.07)	0.839
Hyperlipidemia	0.97 (0.89-1.06)	0.507
Cardiac Status/testing
Native stenosis
Left Main Artery	0.99 (0.90-1.09)	0.809
Proximal Left Anterior Descending Artery	1.04 (0.96-1.12)	0.353
Mid/distal Left Anterior Descending Artery	1.08 (1.00-1.15)	0.037
Left Circumflex Artery	1.19 (1.11-1.28)	<0.001
Right Coronary Artery	1.13 (1.05-1.21)	<0.001
Previous Coronary Artery Bypass Grafting	0.94 (0.85-1.03)	0.188
LVEF (%)
≥50	Referent
≤34	1.68 (1.43-1.98)	<0.001
35-49	1.18 (1.06-1.32)	0.004
NA	1.10 (1.01-1.21)	0.031
Exercise ECG Risk
Low	Referent
High	1.17 (1.05-1.31)	0.005
Uninterpretable	1.18 (0.99-1.41)	0.06
NA	1.04 (0.94-1.15)	0.422
Functional imaging risk
Low	Referent
High	1.01 (0.92-1.12)	0.797
Unknown/NA	0.98 (0.89-1.08)	0.658
Canadian Cardiovascular Society Angina Class
0	Referent
1	1.06 (0.94-1.20)	0.335
2	1.13 (1.02-1.25)	0.022
3	1.19 (1.07-1.33)	0.002
4	1.14 (0.91-1.42)	0.254
Physician-level factors
Referral physician Specialty
Family Physician	Referent
Cardiology	1.06 (0.97-1.16)	0.196
Internal Medicine	1.05 (0.92-1.20)	0.435
Other	0.93 (0.81-1.08)	0.344
Missing	1.03 (0.92-1.15)	0.567
Hospital-level Factors
Mean Cardiac Catherization Volume	1.00 (1.00-1.00)	0.344
Hospital type
Cardiac Catherization, Percutaneous Coronary Intervention, and Coronary Artery Bypass Grafting	Referent
Cardiac Catherization Only	0.75 (0.46-1.23)	0.232
Cardiac Catherization and Percutaneous Coronary Intervention Only	0.94 (0.54-1.62)	0.806

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