Sunday, 10 Dec 2023

CLARIFY Confirms Meds, Watchful Waiting in Angina, Stable CAD

Further evidence supporting conservative management for most patients with stable coronary artery disease (CAD) and angina comes from a new study of more than 30,000 patients in the prospective CLARIFY registry.

Among those with angina at baseline, symptoms disappeared without coronary revascularization in 39.6% at 1 year, with further decreases each year.

At 5 years, 33.9% of these patients still had angina symptoms, 12.3% had had a myocardial infarction (MI) or undergone revascularization, 8.0% had died, but 45.8% were event-free and angina-free.

Patients whose angina resolved at 1 year with conservative management were not at higher risk for the composite primary outcome of cardiovascular death or nonfatal MI than those who never experienced angina, but had a higher risk for MI.

“It’s perfectly reasonable to have a trial of watchful waiting with medical therapy in patients who have angina and stable coronary artery disease because the risk of events is low, the chance this will regress is very high, and, if it regresses, they have an excellent outcome,” senior author Philippe Gabriel Steg, MD, Hôpital Bichat, Paris, told | Medscape Cardiology.

He noted that trials testing revascularization for stable CAD, such as ISCHEMIA, COURAGE, and BARI 2D, have consistently shown the main benefit to be on quality of life due to the regression of angina. “And since most people with angina will regress spontaneously and most people with stable coronary artery disease don’t even have angina, this emphasizes the value of medical management of stable coronary artery disease.”

As reported July 15 in Circulation, the CLARIFY registry involved 32,691 patients (mean age, 64.2 years) with stable CAD enrolled between November 2009 and June 2010. Of these, 22.1% reported angina at baseline and another 2.0% to 4.8% developed angina each year. Use of secondary prevention drugs was high in the cohort.

Over 5-year follow-up, angina regressed in 7773 patients — most (84.4%) without a new medical intervention. Only 4.5% of angina was controlled by coronary revascularization and 11.1% with increases or changes in antianginal medications.

Among patients with baseline angina who underwent revascularization, percutaneous coronary intervention was more common than bypass surgery (70% vs 30%) but angina was more likely to be resolved at 1 year after surgery (74.6% vs 44.6%; P <.001).

Cardiovascular death and MI occurred in 5.9% of patients whose angina resolved at 1 year with conservative management and 5.3% of those who never had angina (adjusted hazard ratio [aHR], 0.97; 95% CI, 0.82 – 1.15).

MI rates were 3.0% and 2.3%, respectively (aHR, 1.27; 95% CI, 1.00 – 1.60).

Independent predictors of cardiovascular death or MI were persistence of baseline angina (aHR, 1.32; 95% CI, 1.12 – 1.55) and occurrence of angina (aHR, 1.37; 95% CI, 1.11 – 1.70).

Reached for comment, Christopher Granger, MD, Duke University School of Medicine, Durham, North Carolina, said the study is confirmatory but also that he welcomed its less selected registry population for shedding additional light on the issue.

“This study adds to the evidence that medical management is very reasonable and may be the optimal treatment for most of these patients; and it’s partly related to the somewhat surprising finding in this study that many of these patients had resolution of angina with just medical therapy,” he said.

The frequency of angina resolution in the first year, Steg said, suggests the need to lengthen the 1- to 4-week blanking period frequently used in trials testing treatments for angina, including revascularization.

The authors write that it also “shows that medical treatment and disease-modifying interventions may take some time to be effective and relieve symptoms, and the relatively low event rate of patients with stable CAD allows a period of watchful waiting before failure of medical management is declared.”

The finding that 33.9% of patients with baseline angina still had angina symptoms at 5 years, they note, reflects an “unmet need for new more effective antianginal therapy.”

Although not directly addressed by this study, Granger said the “biggest opportunity to improve outcomes is to manage the risk factors and comorbidities most effectively and that includes antithrombotic therapy, basic antianginal therapy, but also treatment of diabetes with drugs proven to improve cardiovascular outcome, treatment with high-intensity statins, treatment with ACE and ARBs, and behavior modification.

“Revascularization is still important for a portion of our population but it’s way less important than we used to think it was.”

Granger observed that misperceptions still remain about the need for revascularization in this population and that financial incentives are there for American cardiologists to do revascularization.

Steg, himself an interventionalist, said there is a financial incentive for revascularization in countries with some element of fee-for-service but, beyond that, there’s also a true belief among interventionalists. “It’s hard to believe that what you’re doing is not useful, so you tend to want to have the vessel open and you tend to believe it is actually helping patients.”

Attitudes are changing, albeit slowly, he said, given that four consecutive large-scale randomized trials have consistently failed to demonstrate a clear outcomes benefit with revascularization.

“I haven’t seen a massive drop in the use of revascularization, so I think the machine is still rolling,” Steg said.

This study was funded by Servier. Steg reports grants from Programme de Recherche Medico Economique and from Instituto de Salud Carlos III; grants and personal fees from Amarin, AstraZeneca, Bayer, Sanofi, Regeneron Pharmaceuticals, and Servier; and personal fees from Amgen, Boehringer Ingelheim, BMS, Idorsia, Novartis, Novo Nordisk, and Pfizer. Co-author disclosures are listed in the paper.

Circulation. Published online July 15, 2021. Full text

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