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When it comes to medical therapy after a coronary revascularization procedure, more is better. Patients started and then maintained indefinitely on more rather than fewer of the drugs identified as optimal medical therapy (OMT) achieve a major survival benefit 10 years later, side affects of doxycycline according to long-term follow-up from an extended analysis of the SYNTAX trial.

For the survival benefit at 10 years, “the present study suggests that at least three types of optimal medical therapy should be maintained for at least 5 years after revascularization,” reported a multinational team of cardiovascular specialists led by Hideyuki Kawashima, MD and Patrick Serruys, MD, who both have affiliations with the department of cardiology of the National University of Ireland, Galway.

The SYNTAX trial was conducted to compare percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) for patients with previously untreated three-vessel and/or left main disease (N Engl J Med 2009;360:961-72). The conclusion from that study, published in 2009 and subsequently reinforced by a 5-year follow-up, was that CABG should remain the standard of care for complex lesions.

Optimal Medical Therapy Defined

In the course of SYNTAX, the impact of OMT on outcome was also evaluated in a subanalysis. At 5 years, there was a mortality advantage for those receiving an antiplatelet drug, a statin, a renin-angiotensin system inhibitor (ACE inhibitor or angiotensin receptor blocker), and a beta-blocker when compared with fewer of these agents.

When an investigator-initiated extension of SYNTAX, called SYNTAXES, was conducted to compare the outcomes of PCI and CABG at 10 years, it also permitted an extended analysis of OMT. Although the primary comparison of SYNTAXES, reported 2 years ago, did not show a significant difference between PCI and CABG for mortality at 10 years, there was a difference for OMT.

When investigators compared treatment with three or more OMT agents with that with two or fewer OMT drugs at 5 years, the result for all-cause death at 10 years translated into a more than 50% relative reduction (hazard ratio, 0.47; = .002). The absolute difference in mortality was a more than 6% reduction (13.1% vs. 19.9%).

OMT Data Offer Major Message

The current study is considered to have a major message for patients as well as physicians.

“OMT even outweighs the survival benefit from revascularization alone, so our patients should convince themselves of the value of rigorous adherence and compliance,” Serruys said in an interview. According to him, these are compelling data for telling patients that OMT “is the best insurance for extended survival.” We now know from these data “the longer, the better.”

The same message from these data extends to physicians.

“I wish I could understand the apparent blind spot physicians have with respect to prescribing OMT despite the overwhelming benefit from multiple clinical trials,” said William E. Boden, MD, professor of medicine, Boston University.

Boden was a coauthor of an editorial accompanying the newly published SYNTAXES subanalysis. In the editorial, he noted that OMT following revascularization and in other high-risk patients “has been unacceptably low,” but he was asked to expand on the lessons from the newly released SYNTAXES subanalysis in an interview.

“There has often been a belief that revascularization negates the need for OMT and that’s why the SYNTAXES trial 10-year mortality reduction — which builds upon an earlier 5-year mortality reduction analysis — is so important,” he said.

Patients Should Take OMT Long Term

These data “should be both a motivator for physicians to prescribe OMT and for patients to remain adherent to OMT,” he said. “It is the best warranty to blunt the progression of atherosclerosis and to reduce subsequent cardiac events.”

For the 10-year subanalysis of OMT in SYNTAXES, the patients were stratified by the number of OMTs they were taking at 5 years after revascularization and then evaluated for survival at 10 years. Of the 1,472 patients available for analysis at 5 years, only 678 (46%) were on OMT. The other 794 patients were not.

Graphically, the Kaplan-Meier survival curve for those on three types of OMT was consistently beneath that of those on four OMTs, but the gap narrowed over time. At the end of 10 years, the advantage of the four-drug OMT was not statistically significant relative to three or fewer (13.1% vs. 12.7%).

Statins and Antiplatelets Show Largest Effect

When analyzed individually and in different combinations, the agents with OMT did not appear to be equal. For example, the biggest survival gap at 10 years was for those who were on an antiplatelet therapy and a statin at 5 years relative to those who were not on either (13.2% vs. 22.6%; = .006). Even after adjustment, there was nearly 45% survival benefit for these two agents (HR, 0.556; P = .02).

Conversely, the 10-year survival advantage for being on a renin-angiotensin system inhibitor at 5 years versus not being exposed to this therapy was small and nonsignificant (14.7% vs. 13.7%; = .651).

The precise proportion of patients who were prescribed and adhered to OMT between 5 years and 10 years is unknown, acknowledged the authors, so conclusions are limited about the added benefit of 10- versus 5-year OMT, although the authors presume that a substantial proportion of those adherent for 5 years would likely continue on these therapies.

It can be said with confidence that those adherent for at least 5 years are more likely to be alive at 10 years than those who are not, according to Boden. He considers these data a call for physicians and all high-risk patients, not just those who have undergone revascularization, to take these standard therapies.

There are plenty of data to “show how poorly we treat patients with OMT,” said Boden, citing several studies. In one, which looked at OMT in a nationally representative sample in the United States, only a third of patients with angina were taking an antiplatelet, a statin, and a beta-blocker, all of which are indicated.

“Hospitalization for revascularization provides an opportune time to capture the attention of patients and their physicians,” he wrote in his editorial. He called OMT “an imperative to optimize clinical outcomes.”

Many of the investigators involved in the SYNTAXES subanalysis, including Serruys, have financial relationships with multiple pharmaceutical companies, including Boston Scientific, which provided the initial funding for the SYNTAX trial. Boden reports no potential conflicts of interest.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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