Nov 12th, 2023

Trials’ results suggest new approaches to reducing CVD risk and symptoms

Three trials provide novel approaches to reduce CVD risk.

From left: Christopher Rajkumar, MD, MRC, Jeffrey L. Carson, MD, MACP; Stefan James, MD.

Investigators during Late-Breaking Science Sessions on Saturday revealed surprising findings in three trials on novel approaches to reduce CVD risk. They found:

Liberal blood transfusion strategy may improve clinical outcomes in patients with acute myocardial infarction and anemia.
Dapagliflozin shows clinical benefit in patients with acute myocardial infarction without diabetes or chronic heart failure.
Percutaneous coronary intervention may provide angina relief in patients with single and multivessel disease without antianginal medication.

Liberal blood transfusion for patients with myocardial infarction and anemia may be considered

Anemia is common in patients with acute myocardial infarction. Whether to transfuse or not is an everyday decision clinicians face. A restrictive red blood cell (RBC) transfusion strategy targeting a hemoglobin concentration above 7 or 8 g/dL is safe in most clinical settings outside of the coronary care unit.

But because ischemic myocardium is vulnerable, evidence suggests patients may benefit from a higher hemoglobin. Would a liberal versus restrictive transfusion strategy improve outcomes in patients with acute myocardial infarction and anemia? That’s the question asked in the Restrictive Versus Liberal Blood Transfusion in Patients With Myocardial Infarction and Anemia: Results of the MINT Trial.

The study randomized 3,506 patients with acute myocardial infarction and anemia (Hb <10 g/dL) from 144 sites throughout the United States, Canada, France, Brazil, New Zealand and Australia, with enrollment between 2017 and 2023, to a restrictive or liberal transfusion strategy.

Patients randomized to the liberal transfusion strategy arm received enough red blood cells to maintain Hb ≥10 g/dL through hospital discharge or 30 days. Transfusion was permitted in patients randomized to the restrictive transfusion strategy arm, but not required, and only when the hemoglobin was <8 g/dL and strongly recommended for patients with Hb <7 g/dL or for ischemic symptoms not controlled with medications.

The primary outcome, a composite of all-cause mortality and recurrent myocardial infarction through 30 days following randomization, occurred in 16.9% of patients in the restrictive transfusion group and in 14.5% in the liberal transfusion group, which yielded a relative risk of 1.16 with a lower confidence interval of 1.00 to an upper confidence interval of 1.35 (p=0.07). Cardiac death occurred in fewer patients in the restrictive transfusion group (5.5%) compared with the liberal transfusion group (3.2%). Heart failure, a major safety concern with blood transfusion post-MI, slightly favored the restrictive transfusion group, 5.8% versus 6.3% in the liberal transfusion group.

Jeffrey L. Carson, MD, MACP“Although we can’t claim a liberal transfusion strategy is superior based on our primary outcome, most of the MINT results suggest that patients with acute myocardial infarction and anemia may potentially benefit from a liberal transfusion strategy without undue risk of harm,” said Jeffrey L. Carson, MD, MACP, the study’s principal investigator, Distinguished Professor of Medicine and Richard C. Reynolds, MD, chair in General Internal Medicine at Rutgers, Robert Wood Johnson Medical School.

After the presentation, the study will be published in the New England Journal of Medicine.

Innovative trial shows dapagliflozin reduces risk of adverse cardiometabolic outcomes in patients with acute myocardial infarction

Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, conferred a significant clinical benefit in patients with myocardial infarction and any degree of left ventricular dysfunction, according to a Registry-Based Randomized Trial of Dapagliflozin in Patients With Acute Myocardial Infarction Without Diabetes (DAPA-MI Trial).

The registry-based, double-blind, placebo-controlled trial enrolled 4,017 people hospitalized for myocardial infarction without known diabetes or established heart failure at 39 sites in Sweden and 64 sites in the United Kingdom from December 2020 to March 2023. Patients were randomized to dapagliflozin 10 mg versus placebo once daily in addition to standard therapy to evaluate the effect on a composite of cardiometabolic outcomes over a median follow-up of 12 months.

At baseline, 72% had ST-elevation myocardial infarction, 9% prior myocardial infarction and 2% prior stroke.

The primary endpoint, a hierarchical composite of death, hospitalization for heart failure, non-fatal myocardial infarction, atrial fibrillation/flutter, new diagnosis of Type 2 diabetes, New York Heart Association Functional Classification at the last visit and body weight decrease ≥5% at the last visit, was determined using the win ratio statistical analysis method. Analysis of the primary hierarchical composite of cardiometabolic outcomes resulted in 34% more wins for dapagliflozin than placebo, with a win ratio of 1.34 (95% CI, 1.20 to 1.50, p<0.001). Treatment effect was consistent across pre-specified subgroups.

Stefan James, MD“Patients with diabetes and heart failure have an indication for dapagliflozin therapy based on evidence from previous trials,” said Stefan James, MD, the study’s lead researcher and professor of cardiology at Uppsala University in Sweden. “Similarly, in patients with acute MI and impaired left ventricular function without prior diabetes and chronic heart failure, dapagliflozin demonstrated significant benefit with regards to improvement in cardiometabolic outcomes compared with placebo.

“The DAPA-MI trial has provided several new learnings on the cardiometabolic benefits of dapagliflozin. We have pioneered the Registry-Based Randomized Clinical Trial trial set up in a large blinded cardiovascular outcome trial recruiting more than 4,000 patients with acute myocardial infarction in only two countries, which is an outstanding achievement. Dapagliflozin should be considered as part of standard secondary prevention therapy for patients with acute myocardial infarction and any degree of left ventricular dysfunction.” The study will be published in the New England Journal of Medicine Evidence following the presentation.

Percutaneous coronary intervention reduced angina symptoms

Percutaneous coronary intervention (PCI) significantly reduced angina symptoms in patients with single and multivessel disease and little or no tolerated antianginal medication, according to Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA-2).

The multicenter, double-blind, placebo-controlled trial conducted in 14 U.K. centers enrolled 301 patients with angina or angina equivalent symptoms, severe coronary stenosis in ≥ 1 vessel and evidence of ischemia: stress imaging or invasive physiology and clinical eligibility for PCI.

At enrollment, patients completed angina and quality of life questionnaires and reported their angina symptom frequency daily using a customized smartphone application. Antianginal medications were stopped. Patients were randomized 1:1 to PCI or a placebo procedure.

Patients then entered a blinded follow-up period in which they and the medical and research teams were blinded to treatment allocation. Antianginal medication initiation and up-titration for angina was triggered by patient conduct and managed by the blinded research team. After 12 weeks of follow-up, angina and quality of life questionnaires, treadmill testing and dobutamine stress echocardiology were repeated prior to unblinding and the return to routine clinical care.

The primary endpoint was an angina symptom score, which was a composite ordinal clinical outcome scale of angina health status derived from the number of episodes of angina reported by the patient on a given day, the units of antianginal medication prescribed on that day and high level category overrides for unblinding due to intolerable angina, acute coronary syndrome and death.

Following randomization, patients in the PCI arm had a significantly lower angina symptom score than those in the placebo arm.

Christopher Rajkumar, MD, MRC“The benefit of angioplasty compared to placebo was equivalent to one full dose of antianginal medication,” said Christopher Rajkumar, MD, MRC, clinical research training fellow in interventional cardiology at Imperial College London and the study’s first author.

Still, a significant percentage of patients (59%) had angina symptoms after undergoing PCI.

“This isn’t a procedure that works for everybody,” said Rasha Al-Lamee, MD, BHF, intermediate research fellow and reader in interventional cardiology at Imperial College London and the study’s chief investigator. “But for patients in whom it does, the benefits are likely to be as soon as the next day.

Overall, “ORBITA-2 showed us that PCI should be included early on in shared decision-making when discussing angina therapy options,” Dr. Al-Lamee said. “For the most benefit from PCI, you have to offer it early in their treatment algorithm.” The study will be published in the New England Journal of Medicine after the presentation.