Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study

Abstract

Background Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown. Methods The Dual Antiplatelet Therapy Study, a double-blind trial, randomized 11,648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, beta blocker and angiotensin converting enzyme inhibitor/angiotensin receptor blocker use in patients with an ACC/AHA class I indication for each medication. Per protocol, all patients were treated with aspirin 75–325 mg daily. Endpoints included myocardial infarction (MI), major adverse cardiovascular and cerebrovascular events (MACCE) and GUSTO moderate or severe bleeding events. Results Of 11,643 randomized patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced MI compared with placebo in both groups (on OMT 2.1% vs 3.3%, HR 0.64, CI 0.48–0.86, p=0.003; off OMT 2.2% vs 5.2%, HR 0.41, CI 0.29–0.58, p <0.001; interaction p=0.103). Comparing continued thienopyridine vs placebo, rates of MACCE were 4.2% vs 5.0% among patients on OMT (HR 0.82, CI 0.66–1.02, p=0.077) and 4.5% vs 7.0% among those off OMT (HR 0.63, CI 0.49–0.82, p<0.001; interaction p=0.250); rates of bleeding for thienopyridine vs placebo in patients on OMT were 2.2% vs 1.0% (HR 2.13, CI 1.43–3.17, p<0.001) and in patients off OMT were 2.8% vs 2.2% (HR 1.30, CI 0.88–1.92, p=0.189; interaction p=0.073). Overall, patients on OMT had lower rates of MI (2.7% vs 3.7%, p=0.003), MACCE (4.6% vs 5.7%, p=0.007) and bleeding (1.6% vs 2.5%, p<0.001) compared with patients off OMT. Rates of stent thrombosis (0.8% vs 1.0%, p=0.171) and death (1.6% vs 1.9%, p=0.155) did not differ. Conclusions Continued thienopyridine therapy reduced the rate of MI regardless of OMT status and had consistent effects on reduction in MACCE and increased bleeding. Trial Registration https://clinicaltrials.gov, #NCT00977938

The prevalence, predictors and outcomes of guideline‐directed medical therapy in patients with acute myocardial infarction undergoing PCI, an analysis from the PROMETHEUS registry

“…Therefore, patients with anemia were likely underprescribed GDMT at discharge when considering bleeding risk and intolerance of multiple medications. We also identified increased BMI and STEMI presentation as independently associated with greater GDMT prescription, which is similar to a previous study demonstrating an association of higher weight and ACS as indication of index PCI with higher rates of GDMT use …”

“…Abbreviations: MACE, major adverse cardiac event; aHR, adjusted hazard ratio; CI, confidence interval; LVEF, left ventricular ejection fraction demonstrating an association of higher weight and ACS as indication of index PCI with higher rates of GDMT use. 21 Our findings were similar to a previous study demonstrating that GDMT use was associated with lower 1-year MACE and mortality in patients with ACS. 24 Notably, the risk of all-cause death was 39% lower in patients receiving GDMT vs. non-GDMT at 1 year, whereas we observed a 25% reduction in the risk of recurrent MI.…”

“…We identified hypertension, prior PCI, anemia and CKD as independent factors for underprescription of GDMT at discharge. Similarly, Resor et al reported that hypertension, prior MI, prior PCI and renal insufficiency were associated with underutilization of GDMT, and attributed these factors to regional differences in prescribing patterns and intolerance of multiple medications in patients with more comorbidities. Indeed, patients with high‐risk cardiovascular diseases more often have comorbidities such as hyperlipidemia, DM, PAD, CKD, and congestive heart failure, however, it should be noted that these high‐risk patients tend to derive more clinical benefit from GDMT use.…”

Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network meta-analysis

“…Due to the time span across which these studies were completed, patient population changed substantially, as did concomitant therapy, which may interact with the efficacy of antithrombotic treatment. [49] Important sources of heterogeneity include different times from index ACS event to trial enrollment; the advent of fibrinolysis and PCI; and the use of statins, beta blockers, and ACE inhibitors in both the acute and chronic settings following MI. These limitations are inescapable, and detract from the precision of our estimates.…”

Long-term dual antiplatelet therapy and concomitant optimal medical therapy following percutaneous coronary intervention

“…In line with the strategy to search for factors helping to individualize the optimal DAPT regimen patient-bypatient, Resor and colleagues recently investigated the impact of optimal medical therapy (OMT) on the treatment effect of DAPT (26). This analysis was conducted in the setting of all patients enrolled in the randomized DAPT study, including those treated with DES or BMS.…”