Restrictive access to clopidogrel and mortality following coronary stent implantation

Abstract

Background: In Canada, access to clopidogrel is restricted by most provincial drug insurance plans in order to contain costs. Until April 2007, the Régie de l'assurance maladie du Québec (RAMQ) Prescription Drug Insurance Plan reviewed special access forms before approving reimbursement for clopidogrel prescriptions. We investigated the impact of this restrictive process on patient's filling of prescriptions and on all-cause mortality following coronary stenting.

Methods: We analyzed prescriptions filled and all-cause mortality in the year following a percutaneous coronary intervention among patients who underwent stent implantation between January 2000 and September 2004. We obtained administrative data from the RAMQ databases. We included patients who filled at least 1 prescription for a nonrestricted cardiovascular drug after hospital discharge. We used Cox proportional models to compare mortality rates as a function of delayed or absent outpatient clopidogrel therapy.

Results: Of 13,663 patients, 1571 (11.5%) did not fill any clopidogrel prescription despite filling at least 1 nonrestricted cardiovascular drug prescription after a percutaneous coronary intervention, and 1174 (8.6%) patients filled their clopidogrel prescription with a delay of at least 1 day (median delay 5 days) after filling the nonrestricted cardiovascular drug prescription. After controlling for pertinent covariables, not filling a clopidogrel prescription (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.35-2.15) and filling with a delay (HR 1.34, 95% CI 1.01-1.80) were associated with a significant increase in all-cause mortality.

Interpretation: Restricted access to clopidogrel was associated with about 20% of patients either not receiving clopidogrel or receiving therapy after a delay. Delay or absence of clopidogrel therapy increased the risk of all-cause mortality after percutaneous coronary intervention with stenting.

Figure 1: Selection of the study population. Note: RAMQ = Régie de l'assurance maladie du Québec.

Figure 2: Survival curves for patients who underwent percutaneous coronary intervention with stenting between January 2000 and December 2004. Note: CI = confidence interval. *No. at risk excludes patients who became ineligible for drug coverage during the previous period of follow-up.

Figure 3: Crude and adjusted risk of death among patients who underwent stent implantation between January 2000 and September 2004. *Adjusted (forward stepwise selection) for sex; age; Régie de l'assurance maladie du Québec drug plan maximum monthly copayment; chronic disease score; length of stay in hospital for stent implantation; no. of days in hospital in the year before stent implantation; no. of visits to emergency room, family physician, cardiologist, other specialists in the year before stent implantation; concomitant acetylsalicylic acid use; compliance to nonrestrictive cardiovascular drugs and year of stent implantation. †Despite appearing to be nonsignificant, the adjusted hazard ratios for adherence to nonrestricted cardiovascular drug therapy, hospital length of stay, number of other specialist visits and admission to hospital in the year before stent implantation were each significant (95% CI excluding 1).