CLARIFY at 5 Years: Angina Predictive of MI/CV Death Only in Prior MI Patients

PARIS, France—Long-term follow-up of patients across the spectrum of chronic coronary syndromes (CCS) indicates that rates of cardiovascular death and nonfatal MI are very low, but also that risk factor control is far from optimal in this group.

And in a key new finding, this may be particularly problematic in patients with prior MI experiencing angina, said Emmanuel Sorbets, MD (Hôpital Avicenne, Bobigny, France), who presented the final 5-year data from CLARIFY here at the European Society of Cardiology (ESC) Congress 2019. While angina appeared to have no association with prognosis in the bulk of the patients in this registry, new angina symptoms in prior MI patients tracked with a significantly increased risk of subsequent MI or CV death.

“We [already] know that a patient with a prior MI is at high risk,” Sorbets said in a morning press conference. “One year, 2 years, 5 years later when the patient has, again, angina, of course we will explore it with echo, with scintigraphy. And maybe the result will be okay, everything is fine, and then we will [say we’ll] see him later. But actually, no, the patient is still at higher risk than others, even if the assessment is quite good.”

The CLARIFY analysis, which was published simultaneously in the European Heart Journal, incorporates the “chronic coronary syndrome” terminology introduced in new ESC guidelines released earlier this week. Its authors made the decision to change their paper and presentation to include the new term just “a few days ago,” Sorbets said, pointing out that in fact the full name for CLARIFY (prospective observational longitudinal registry of patients with stable coronary artery disease) includes the wording that CCS has replaced.

But updating the paper to reflect the shift in language made sense, he said, since CLARIFY illustrates the message behind the change—namely, that “there is no one type of stable CAD.”

Some Clarity on CCS

CLARIFY enrolled 32,703 patients from 45 countries, with participating physicians each prospectively enrolling 10 to 15 patients between 2009 and 2010. Medical care was at the discretion of the treating physician, with patients undergoing yearly follow-up. By design, the trial enrolled a wide range of patients previously considered to have “stable” CAD—these included prior myocardial infarction or revascularization more than 3 months earlier, proven symptomatic myocardial ischemia, or angiographic coronary stenosis > 50%.

Certain baseline characteristics of this cohort were notable, said Sorbets. More than 95% of patients were taking an antiplatelet drug, more than four out of five were taking a statin, and roughly three out of four patients were taking beta-blockers and ACE inhibitors/angiotensin receptor blockers, respectively. But despite high use of guideline-directed therapy, achievement of risk factor targets was less than optimal.

Using conventional targets, just 65% of patients had their blood pressure controlled to below 140/90 mm Hg, only 61% had LDL-cholesterol levels less 100 mg/dL, and just 42% had both risk factors at target levels. Using the more stringent recommendations set out in the most recent guidelines, risk-factor control was nominal, with only 7.4% of patients reaching a blood pressure target of less than 130/80 mm/Hg and an LDL cholesterol level below 70 mg/dL.

Over a median of 5 years, 8% of the cohort had a primary-endpoint event (CV death or nonfatal MI), yielding an event rate of 1.7 per 100 person-years. Despite different baseline characteristics and care, long-term event rates in men and women were similar, Sorbets noted.

Conventional risk factors were predictors of poor outcomes, but so too were a history of heart failure hospitalization, atrial fibrillation, and peripheral artery disease, “suggesting that these comorbidities must not be considered as incidental in chronic coronary syndrome patients,” the authors write in their paper

The most important finding, Sorbets said, was that angina was associated with worse prognosis only in patients with prior MI and not in patients without prior MI. “This is new, and this is strongly significant even after multivariate adjustment,” said Sorbets.

Fine-tuning Care

“One of the take homes from this study is that we have a very easy, high-risk factor here,” said Sanjay Sharma, MD (St George’s, University of London, England), commenting on the CLARIFY data at the press conference. “If a patient who has had a prior myocardial infarction presents with chest pain, we know without doing any diagnostic tests that we’re dealing with a high-risk individual who requires intensive investigation and aggressive management of symptoms and risk factors.”

Elaborating to TCTMD, Sharma pointed out that a range of expensive tests like myocardial perfusion scintigraphy and cardiac MR stress perfusion are often ordered in patients with chest pain. What CLARIFY offers, across a broad population of patients, is a way to fine-tune care. If the patient presenting with chest pain has had a prior MI, “we know from this paper that this individual needs very timely investigation such as a coronary angiogram, leading perhaps to a second revascularization, and [for us] to address whether we have achieved targets when it comes to blood pressure and hypercholesterolemia.”

This last aspect is important, Sorbets observed, since in many cases, chest-pain workup in these higher-risk patients will reveal no new disease warranting an intervention. This doesn’t mean the patient is fine, he said. “Maybe we have to organize a new follow-up 3 months later, just to be sure, and we can explain to the patients: ‘Yes, the assessment is normal, but don’t stop your medication.’”

This is the opportunity to try to get these patients to targets since, according to these data, it’s unlikely they’re already there, Sorbets concluded.