Intensive medical treatment failed to reduce major adverse cardiovascular events in women with suspected ANOCA/INOCA over 2.5 years.

This randomized controlled trial evaluated the efficacy of intensive medical treatment (IMT) versus usual care (UC) in women with suspected ANOCA/INOCA (angina due to suspected ischemia with no obstructive coronary artery disease). The study was conducted across 71 sites in the USA, enrolling a total sample size of 2,476 women. The population consisted of patients with a mean age of 64 years who presented with well-controlled blood pressure and low-density lipoprotein cholesterol levels at baseline. Recruitment for the trial was lower than originally planned, which impacted the overall statistical power of the analysis.

The intervention arm received intensive medical treatment comprising high-intensity statin therapy, an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB), and aspirin. The comparator group received usual care. At baseline, relatively high rates of statin and ACEi/ARB use were already present in the study population, which may have influenced the observed outcomes. The primary outcome was defined as major adverse cardiovascular event (MACE), a composite endpoint including all-cause death, myocardial infarction, stroke or transient ischemic attack, and hospitalization for angina or heart failure. Secondary outcomes included the individual components of the primary outcome, quality of life, and a win ratio.

Follow-up for the primary outcome analysis was 2.5 years. During this period, a total of 421 MACE events occurred. Of these, 221 events were observed in the IMT group and 200 events in the UC group. The hazard ratio for MACE in the IMT group versus the UC group was 1.13, with a 95% confidence interval ranging from 0.94 to 1.37. The p-value for this comparison was 0.20, indicating no statistically significant difference between the two groups. Consequently, intensive medical treatment did not improve primary outcomes compared to usual care in this cohort.

Regarding secondary outcomes, no significant differences were reported between the IMT and UC groups. Specific effect sizes, absolute numbers, and p-values for these secondary endpoints were not reported in the available data. Safety and tolerability findings, including rates of adverse events, serious adverse events, discontinuations, and general tolerability, were not reported in the study results. A sensitivity analysis addressing potential contamination yielded an estimated hazard ratio of 0.74 for IMT versus UC, with a 95% confidence interval of 0.352 to 1.558 and a p-value of 0.43.

Several methodological limitations must be considered when interpreting these results. The study population was characterized by an aged demographic with well-controlled cardiovascular risk factors at baseline, which may limit generalizability to patients with more aggressive disease profiles. The high baseline use of statins and ACEi/ARBs suggests that the incremental benefit of the intensive regimen was tested in a setting where standard therapies were already widely adopted. Crucially, the limited power of the study precludes concluding that intensive medical treatment may not be helpful; the absence of a significant difference could be due to insufficient sample size rather than a true lack of effect.

These findings support the need for further investigation in this population, which bears a high burden of angina hospitalization, significant health resource consumption, and poor quality of life. The results do not currently support the routine addition of intensive medical treatment beyond usual care for women with suspected ANOCA/INOCA based on this trial alone. Further research is required to determine if specific subgroups or different treatment intensities might yield different outcomes. Clinicians should interpret these results with caution, acknowledging the uncertainty regarding the potential utility of IMT in this specific clinical context.

Key questions remain unanswered regarding the optimal management strategies for women with suspected ANOCA/INOCA who do not respond to standard therapies. The lack of reported safety data limits the ability to fully assess the risk-benefit profile of the intensive regimen in this specific population. Future studies should aim to address the limitations of this trial, including the baseline characteristics of the participants and the statistical power to detect modest treatment effects.