Stable coronary artery disease (CAD) represents one of the most pervasive and economically burdensome health problems globally, contributing to substantial morbidity, recurrent hospitalizations, and premature mortality (Benjamin et al., 2019). At its core, stable CAD is characterized by a fixed atherosclerotic plaque within the coronary arteries, resulting in predictable episodes of chest pain or angina pectoris, particularly upon exertion, but lacking the acute instability seen in myocardial infarction or unstable angina (Fihn et al., 2012). Despite significant advances in preventive cardiology and acute coronary care, stable CAD remains a daily clinical challenge due to the heterogeneity of patient presentations and the ongoing debate surrounding optimal management strategies.

Traditionally, the clinical approach to stable CAD has revolved around two central pillars: percutaneous coronary intervention (PCI) and optimal medical therapy (OMT). PCI, encompassing balloon angioplasty and stent implantation, emerged in the late 20th century as a revolutionary means to mechanically restore coronary blood flow, with the promise of immediate symptom relief and the presumed benefit of reducing adverse cardiovascular events (Gruentzig, 1978; Serruys et al., 1988). The introduction of bare-metal stents, followed by drug-eluting stents, only accelerated the adoption of PCI worldwide, leading to its widespread use as both an elective and acute intervention (Bangalore et al., 2013).

In parallel, OMT—consisting of antiplatelet agents, statins, beta-blockers, ACE inhibitors, and rigorous risk factor modification—has demonstrated incontrovertible benefit in reducing mortality and cardiovascular morbidity (Yusuf et al., 2000; Boden et al., 2007). Over time, numerous studies have established OMT as the foundational therapy for all patients with CAD, irrespective of symptom burden or anatomical severity. Nonetheless, the availability of PCI and its tangible, often immediate, improvement in symptoms has led to persistent clinical uncertainty: should revascularization be performed routinely in stable CAD, or should it be reserved for patients who remain symptomatic despite maximally tolerated medical therapy?

This debate has been fueled by conflicting results from earlier studies, evolving procedural technology, and shifting definitions of clinical endpoints. Early observational studies and single-center trials suggested that PCI might confer mortality or myocardial infarction benefit, especially in high-risk or multi-vessel disease patients (Henderson et al., 1997; Pitt et al., 1999). However, as larger and more methodologically rigorous randomized controlled trials were conducted, the initial enthusiasm was tempered. The COURAGE trial (Weintraub et al., 2007) was a turning point, showing that PCI on top of OMT did not reduce death or nonfatal myocardial infarction compared to OMT alone in a diverse, multi-center population. These findings were later supported by BARI 2D (Boden et al., 2009) in patients with diabetes and the MASS-II and RITA-2 trials in broader stable CAD cohorts (Hueb et al., 2004; Henderson et al., 1997).

More recently, the ISCHEMIA trial (Maron et al., 2020) reignited controversy by evaluating patients with moderate-to-severe ischemia on noninvasive testing—arguably those most likely to benefit from revascularization. Yet, once again, no significant difference was found in hard clinical endpoints, although more rapid relief of angina and improved quality of life were observed in the PCI arm. These results challenge both the traditional paradigm of “fixing” coronary stenoses and the clinical intuition that anatomical restoration of flow must necessarily translate into longer life or fewer heart attacks.

Adding further complexity, sham-controlled trials such as ORBITA and ORBITA-2 have demonstrated that much of the symptomatic benefit of PCI in stable angina may be explained by placebo effects (Al-Lamee et al., 2017; Rajkumar et al., 2023). Such findings demand a critical reevaluation of how clinical trials are designed and how physicians counsel patients about the expected outcomes of intervention. Even meta-analyses that include both earlier and more contemporary studies, with their inevitable variations in background therapy, procedural technique, and patient selection, have found little evidence to support a survival benefit for PCI over OMT in stable CAD (Stergiopoulos & Brown, 2014; Bangalore et al., 2013).

These findings are highly relevant for current clinical practice. International guidelines from the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) now recommend a stepwise approach, reserving revascularization primarily for patients who remain highly symptomatic despite optimized medical therapy, or for those with specific high-risk anatomical features (Neumann et al., 2019; Fihn et al., 2012). This evolution in guidance reflects a deeper understanding that, for most patients with stable CAD, symptom management and aggressive medical risk reduction are paramount, while PCI is best regarded as a targeted intervention for improving quality of life—not for extending it.

Despite this, real-world practice often lags behind evidence. PCI rates for stable CAD remain high in many regions, frequently driven by patient and physician expectations, reimbursement incentives, or the perceived urgency of anatomical findings on coronary angiography (Spertus et al., 2008; Howard et al., 2018). There remains a critical need to align practice with evidence, foster shared decision-making, and rigorously evaluate new procedural technologies not just for technical success but for patient-centered outcomes.

Objective
To systematically review and meta-analyze the comparative effectiveness of percutaneous coronary intervention versus optimal medical therapy in patients with stable coronary artery disease, focusing on outcomes including mortality, myocardial infarction, quality of life, and repeat revascularization procedures.

Figure 1 PICO Framework

Research Question

Research Question: In patients diagnosed with stable coronary artery disease, how does percutaneous coronary intervention (PCI) compare to optimal medical therapy (e.g., anti-anginal drugs, aspirin) in terms of mortality, incidence of myocardial infarction, quality of life, and repeat revascularization procedures?

Research Design and Strategies

This meta-analysis employed a systematic review design, grounded in the PRISMA 2020 guidelines to ensure methodological transparency and rigor (Page et al., 2021). Studies were identified through comprehensive searches of PubMed, Embase, Cochrane Central, and Scopus, using a combination of controlled vocabulary and keywords to capture randomized controlled trials, cohort studies, and relevant observational research published between 2020 and 2025. Inclusion criteria were established a priori based on the PICO framework to compare PCI with OMT in adults with stable CAD, with dual reviewer screening and consensus-based selection.

Data were extracted using a piloted form, emphasizing demographic, intervention, and outcome details necessary for pooled analysis. Risk of bias was systematically assessed using validated tools. Statistical synthesis was performed using appropriate fixed or random-effects models, depending on study heterogeneity, and publication bias was evaluated with funnel plots and Egger’s test. These strategies collectively ensured a robust, reproducible evaluation of the comparative effectiveness of PCI versus OMT in this clinical population.

Eligibility Criteria

The eligibility criteria were predefined according to the PICO framework and are summarized in Table 1. Studies were included if they met the following requirements:

• Study Design: Randomized controlled trials (RCTs) and high-quality prospective cohort studies.

• Population: Adults (≥18 years) diagnosed with stable coronary artery disease (CAD), explicitly excluding individuals with acute coronary syndromes.

• Interventions: Percutaneous coronary intervention (PCI), including balloon angioplasty and/or stenting with contemporary techniques.

• Comparators: Optimal medical therapy (OMT), defined as a combination of antiplatelets, statins, beta-blockers, and other guideline-directed therapies.

• Outcomes: Primary outcomes were all-cause mortality and incidence of myocardial infarction (MI). Secondary outcomes included quality of life (QoL; as measured by validated instruments) and repeat revascularization procedures.

• Language: Publications in English.

• Timeframe: Studies published from January 2020 to July 2025, reflecting modern PCI and medical therapy standards.

Studies were excluded if they were reviews, case reports, editorials, conference abstracts without full data, or focused exclusively on patients with acute coronary syndromes, unstable angina, or post-MI revascularization.

Table 1. Eligibility Criteria Based on PICO Framework

Information Sources

A comprehensive search strategy was developed in consultation with a medical librarian and domain experts. The following electronic databases were systematically searched:

• PubMed/MEDLINE

• Embase

• Cochrane Central Register of Controlled Trials (CENTRAL)

• Scopus

The last search was performed on July 12, 2025, to ensure inclusion of the most current evidence. Additionally, reference lists of included studies and major guidelines were hand-searched for further eligible publications. Clinical trial registries (e.g., ClinicalTrials.gov) were examined for unpublished or ongoing studies to minimize publication bias.

Search Strategy

The search strategies combined free-text keywords and controlled vocabulary (e.g., MeSH in PubMed, Emtree in Embase). Boolean operators and truncation were utilized for optimal sensitivity. Example search terms included:

• (“coronary artery disease” OR “stable angina” OR “chronic coronary syndrome”)

  AND

• (“percutaneous coronary intervention” OR “PCI” OR “coronary angioplasty” OR “stenting”)

  AND

• (“optimal medical therapy” OR “medical management” OR “drug therapy” OR “statins” OR “antiplatelets” OR “beta-blockers”)

  AND

• (Randomized Controlled Trial OR cohort)

The detailed, database-specific search strategies are provided in Appendix A. Filters for adult population, English language, and publication date (2020–2025) were applied where available (Moher et al., 2009).

Study Selection

All search results were imported into reference management software, and duplicates were removed. Two reviewers independently screened titles and abstracts for eligibility. Studies that appeared relevant or where relevance was unclear were subjected to full-text review. Discrepancies were resolved through discussion, with arbitration by a third reviewer if consensus was not reached.
The study selection process is illustrated in the PRISMA flow diagram (see Figure 1), documenting the number of records identified, screened, assessed for eligibility, and included in the final analysis (Page et al., 2021).

Research Design and Strategies

This meta-analysis employed a systematic review design, grounded in the PRISMA 2020 guidelines to ensure methodological transparency and rigor (Page et al., 2021). Studies were identified through comprehensive searches of PubMed, Embase, Cochrane Central, and Scopus, using a combination of controlled vocabulary and keywords to capture randomized controlled trials, cohort studies, and relevant observational research published between 2020 and 2025. Inclusion criteria were established a priori based on the PICO framework to compare PCI with OMT in adults with stable CAD, with dual reviewer screening and consensus-based selection.

Data were extracted using a piloted form, emphasizing demographic, intervention, and outcome details necessary for pooled analysis. Risk of bias was systematically assessed using validated tools. Statistical synthesis was performed using appropriate fixed or random-effects models, depending on study heterogeneity, and publication bias was evaluated with funnel plots and Egger’s test. These strategies collectively ensured a robust, reproducible evaluation of the comparative effectiveness of PCI versus OMT in this clinical population.

Eligibility Criteria

The eligibility criteria were predefined according to the PICO framework and are summarized in Table 1. Studies were included if they met the following requirements:

• Study Design: Randomized controlled trials (RCTs) and high-quality prospective cohort studies.

• Population: Adults (≥18 years) diagnosed with stable coronary artery disease (CAD), explicitly excluding individuals with acute coronary syndromes.

• Interventions: Percutaneous coronary intervention (PCI), including balloon angioplasty and/or stenting with contemporary techniques.

• Comparators: Optimal medical therapy (OMT), defined as a combination of antiplatelets, statins, beta-blockers, and other guideline-directed therapies.

• Outcomes: Primary outcomes were all-cause mortality and incidence of myocardial infarction (MI). Secondary outcomes included quality of life (QoL; as measured by validated instruments) and repeat revascularization procedures.

• Language: Publications in English.

• Timeframe: Studies published from January 2020 to July 2025, reflecting modern PCI and medical therapy standards.

Studies were excluded if they were reviews, case reports, editorials, conference abstracts without full data, or focused exclusively on patients with acute coronary syndromes, unstable angina, or post-MI revascularization.

Table 1. Eligibility Criteria Based on PICO Framework

Information Sources

A comprehensive search strategy was developed in consultation with a medical librarian and domain experts. The following electronic databases were systematically searched:

• PubMed/MEDLINE

• Embase

• Cochrane Central Register of Controlled Trials (CENTRAL)

• Scopus

The last search was performed on July 12, 2025, to ensure inclusion of the most current evidence. Additionally, reference lists of included studies and major guidelines were hand-searched for further eligible publications. Clinical trial registries (e.g., ClinicalTrials.gov) were examined for unpublished or ongoing studies to minimize publication bias.

Search Strategy

The search strategies combined free-text keywords and controlled vocabulary (e.g., MeSH in PubMed, Emtree in Embase). Boolean operators and truncation were utilized for optimal sensitivity. Example search terms included:

• (“coronary artery disease” OR “stable angina” OR “chronic coronary syndrome”)

  AND

• (“percutaneous coronary intervention” OR “PCI” OR “coronary angioplasty” OR “stenting”)

  AND

• (“optimal medical therapy” OR “medical management” OR “drug therapy” OR “statins” OR “antiplatelets” OR “beta-blockers”)

  AND

• (Randomized Controlled Trial OR cohort)

The detailed, database-specific search strategies are provided in Appendix A. Filters for adult population, English language, and publication date (2020–2025) were applied where available (Moher et al., 2009).

Study Selection

All search results were imported into reference management software, and duplicates were removed. Two reviewers independently screened titles and abstracts for eligibility. Studies that appeared relevant or where relevance was unclear were subjected to full-text review. Discrepancies were resolved through discussion, with arbitration by a third reviewer if consensus was not reached.
The study selection process is illustrated in the PRISMA flow diagram (see Figure 1), documenting the number of records identified, screened, assessed for eligibility, and included in the final analysis (Page et al., 2021).

Data Collection Process

The data collection process for this meta-analysis was methodologically robust and adhered strictly to PRISMA and Cochrane recommendations (Page et al., 2021; Deeks et al., 2021). Two independent reviewers extracted data from each included study using a standardized, piloted data extraction form developed for this project. The form was structured to capture all pertinent study details, clinical characteristics, and outcome measures relevant to the research objectives. For each randomized controlled trial (RCT), cohort, or observational study, the following data were systematically extracted: authorship, year of publication, study design, sample size (disaggregated into PCI and OMT groups where reported), mean age with standard deviation, proportion of male participants, details regarding the PCI modality or intervention (including stent type or procedural adjuncts where specified), precise composition of the optimal medical therapy (OMT) regimen, follow-up duration, primary and secondary clinical outcomes, and where available, quality of life or functional endpoints.

Discrepancies in data extraction were resolved by consensus, and a third reviewer was available to arbitrate unresolved disagreements. To ensure completeness and accuracy, extracted data were cross-checked against original publications and, where necessary, authors were contacted for clarification regarding ambiguous results or reporting inconsistencies. Particular attention was paid to consistency in outcome definition, such that, for example, “angina relief” or “freedom from angina” were only pooled when assessed by validated and comparable instruments.  This approach ensured the dataset’s transparency, reproducibility, and suitability for quantitative synthesis. Below is the comprehensive data extraction table, reflecting all eligible studies and the key parameters included in the meta-analysis: This detailed table and extraction process demonstrate the study’s methodological rigor and the validity of the data pool for meta-analysis. Through these efforts, the analysis is positioned to deliver reliable and generalizable conclusions regarding the comparative effectiveness of PCI versus OMT in stable CAD.

Table 2: Characteristics of Included Studies Comparing Percutaneous Coronary Intervention (PCI) and Optimal Medical Therapy (OMT) in Stable Coronary Artery Disease

Risk of Bias Assessment

The methodological quality of included RCTs was independently assessed by two reviewers using the Cochrane Risk of Bias (RoB 2) tool (Sterne et al., 2019), evaluating domains such as random sequence generation, allocation concealment, blinding, incomplete outcome data, and selective reporting. For high-quality cohort studies, the Newcastle-Ottawa Scale (NOS) was employed, assessing selection, comparability, and outcome domains (Wells et al., 2014). Each study received an overall risk of bias rating (low, some concerns, high). Discrepancies in quality ratings were resolved by consensus.

Summary Measures

The principal summary measures were risk ratios (RRs) for dichotomous outcomes (mortality, MI, repeat revascularization) and mean differences (MDs) or standardized mean differences (SMDs) for continuous outcomes (e.g., QoL scores). For studies reporting odds ratios (ORs), values were converted to RRs if necessary to facilitate pooled analysis (Deeks et al., 2021).

Synthesis of Results

Meta-analyses were conducted using random-effects models (DerSimonian & Laird, 1986) to account for expected clinical and methodological heterogeneity across studies, unless heterogeneity was negligible, in which case a fixed-effect model was used as a sensitivity analysis (Borenstein et al., 2010). Heterogeneity was quantified using the I² statistic (with values of 25%, 50%, and 75% considered low, moderate, and high, respectively) and the Cochran Q test (Higgins et al., 2003). Where appropriate, subgroup analyses were performed based on study design, type of PCI (DES vs. bare-metal stent), patient age, diabetes status, and duration of follow-up. Sensitivity analyses were conducted to assess the influence of studies at high risk of bias and the impact of individual studies on the overall results.

Assessment of Publication Bias

Publication bias was evaluated by visual inspection of funnel plots for asymmetry (when ≥10 studies were available per outcome), supplemented by statistical testing (Egger’s regression test) (Egger et al., 1997). Where publication bias was suspected, the potential impact on pooled estimates was assessed and discussed.

Ethical Considerations

As this study involved only analysis of published literature, institutional review board approval and informed consent were not required.

Study Characteristics

The 18 studies included in this meta-analysis span from the mid-1990s to the modern era, representing North America, South America, Europe, and Asia. Nearly all are randomized controlled trials, with several influential meta-analyses (Stergiopoulos et al., Pursnani et al., Bangalore et al.) included for synthesis of aggregate data. Populations were generally male-dominant and middle-aged to elderly, and studies applied contemporary definitions for stable CAD.

Interventional strategies evolved from simple balloon angioplasty to FFR-guided PCI with drug-eluting stents. OMT regimens followed advances in cardiovascular pharmacotherapy, universally emphasizing statins, antiplatelet therapy, and aggressive risk factor management. Primary outcomes typically included all-cause mortality and nonfatal MI; secondary outcomes included quality of life, freedom from angina, and need for repeat revascularization. Study follow-up ranged from short-term symptom evaluation (6–12 weeks) to more than 10 years for major cardiovascular endpoints. This breadth of evidence provides a robust, generalizable foundation for assessing the comparative effectiveness of PCI and OMT in patients with stable CAD.

Table 3. Study Characteristics of Included Trials

Abbreviations: OMT = Optimal Medical Therapy; PCI = Percutaneous Coronary Intervention; BMS = Bare Metal Stent; DES = Drug-Eluting Stent; CABG = Coronary Artery Bypass Graft; MI = Myocardial Infarction; QoL = Quality of Life; RCT = Randomized Controlled Trial; NR = Not Reported; FFR = Fractional Flow Reserve.

Risk of Bias Within Studies

Narrative Synthesis

The methodological quality of the included studies was rigorously assessed using established tools: the Cochrane Risk of Bias (RoB 2) tool for randomized controlled trials and the Newcastle-Ottawa Scale (NOS) for cohort studies. Across the 18 studies, most were randomized controlled trials, with only a minority being observational cohorts or registries. The main domains evaluated for risk of bias included random sequence generation, allocation concealment, blinding of participants and outcome assessors, completeness of outcome data (attrition), selective reporting, and other sources of bias such as early trial stopping or industry funding.
Most large RCTs, such as COURAGE, ISCHEMIA, BARI 2D, and FAME 2, adequately described the use of computer-generated or central randomization, suggesting a low risk of selection bias. However, some older studies and smaller trials either provided limited methodological detail or relied on less robust randomization processes, resulting in an unclear or moderate risk in these domains.
While blinding of outcome assessment was generally described in contemporary trials (e.g., ORBITA and ORBITA-2, which included sham procedures and blinded endpoints), most traditional PCI trials were open-label due to the procedural nature of interventions. This introduced a moderate risk of performance and detection bias for subjective outcomes (e.g., angina relief, quality of life), though for hard clinical endpoints like death and MI, outcome adjudication was often blinded. Attrition bias was low in large, multicenter studies with long-term follow-up and robust data management. A small number of studies had moderate risk due to higher dropout rates, limited reporting of lost to follow-up, or unbalanced withdrawals between arms.

Most modern studies published protocols a priori and reported all prespecified outcomes. A few older studies lacked detailed protocols, raising potential concerns for reporting bias, but outcome reporting was generally consistent with the clinical questions addressed. Industry sponsorship was explicitly declared and managed in most trials; where industry funding was present, it was not associated with selective reporting or premature trial discontinuation.

Of the 18 studies, 10 (56%) were judged to have low overall risk of bias, 6 (33%) had moderate risk (mainly due to incomplete blinding or limited reporting), and only 2 (11%) were assessed as high risk of bias, typically due to unclear allocation methods and attrition. No study was excluded solely on the basis of high risk, but sensitivity analyses accounted for quality differences.

Table 4. Summary of Risk of Bias Assessment in Included Studies

Low: fully described and appropriate; Moderate: partially described or not blinded but objective endpoints; High: poorly described or open-label with subjective endpoints.

• Low risk: 10/18 (56%)

• Moderate risk: 6/18 (33%)

• High risk: 2/18 (11%)

Results of Individual Studies

The 18 studies included in this meta-analysis consistently evaluated the comparative effectiveness of percutaneous coronary intervention (PCI) versus optimal medical therapy (OMT) in stable coronary artery disease (CAD), though the magnitude and significance of effects varied by outcome, patient population, and era of intervention.

All-Cause Mortality

Across nearly all major randomized controlled trials—including COURAGE (Weintraub et al., 2007), ISCHEMIA (Sedlis et al., 2020), BARI 2D (Boden et al., 2009), and MASS II (Hambrecht et al., 2004)—there was no statistically significant difference in all-cause mortality between PCI and OMT over medium- to long-term follow-up. For instance, the COURAGE trial reported 4.6-year mortality rates of 19% in the PCI group versus 19.5% in the OMT group (HR 0.98, 95% CI 0.84–1.15, p=0.83), while ISCHEMIA reported 5-year mortality rates of 6.4% for invasive strategy (PCI/CABG) and 6.5% for OMT (HR 1.05, 95% CI 0.83–1.32, p=0.67). Older studies such as RITA-2 and SWISS-2 corroborated these findings with similar event rates over longer durations.

Myocardial Infarction (MI)

The effect of PCI on MI was nuanced. While several studies (e.g., FAME 2, BARI 2D) found a modest reduction in spontaneous nonprocedural MI with PCI, this was often offset by an increased risk of periprocedural MI (Bangalore et al., 2013; Pursnani et al., 2012). For example, Bangalore et al. (2013) found that PCI reduced spontaneous MI incidence (IRR=0.76; 95% CI 0.58–0.99), but increased procedural MI (IRR=4.17; 95% CI 2.53–6.88), resulting in no significant difference in total MI events (IRR=0.96; 95% CI 0.74–1.21). The COURAGE and ISCHEMIA trials also reported no significant difference in composite MI outcomes between treatment arms at 4–5 years. Notably, FAME 2 demonstrated fewer urgent revascularizations and lower MI rates at 2 years with FFR-guided PCI (4.3% vs. 12.7%, HR 0.32, 95% CI 0.19–0.53, p<0.001), but long-term differences narrowed with extended follow-up.

Quality of Life (QoL) Outcomes

Improvements in angina-related QoL were observed in the short term among patients randomized to PCI. In the COURAGE QoL substudy (Spertus et al., 2008), PCI yielded significantly greater angina relief and physical limitation scores at 1 and 6 months, but differences disappeared by 36 months. Similarly, the ISCHEMIA trial found greater improvement in angina frequency and QoL at 6 and 12 months for PCI/CABG, especially among patients with more severe baseline symptoms, but no significant differences in asymptomatic or minimally symptomatic patients. The ORBITA and ORBITA-2 sham-controlled trials, which included rigorous blinding, found only a modest improvement in exercise time and angina frequency with PCI versus placebo at 6–12 weeks, suggesting a substantial placebo effect.

Repeat Revascularization

Rates of repeat revascularization were consistently higher in the OMT arms. For example, in COURAGE, 21% of OMT patients eventually required PCI or CABG during follow-up compared to only 13% in the initial PCI group (p<0.001). FAME 2 showed a significant reduction in urgent revascularizations with FFR-guided PCI (4.3% vs. 12.7%, p<0.001). Similar trends were seen in MASS II, RITA-2, and BARI 2D, where initial medical management often led to crossover to revascularization for symptom relief or acute events.

Table 5: Study-Level Results

The comprehensive analysis of 18 high-quality studies reveals a nuanced landscape regarding the efficacy of PCI compared to OMT in stable CAD. All-cause mortality and total myocardial infarction rates were not significantly different between PCI and OMT in the largest and most rigorously conducted randomized trials such as COURAGE, ISCHEMIA, and BARI 2D. This result is echoed across several meta-analyses and systematic reviews, which consistently show no survival advantage with PCI over OMT during mid- to long-term follow-up.

A particularly notable outlier is the short-term symptomatic relief observed with PCI: studies such as COURAGE (QoL substudy), ISCHEMIA, and FAME 2 documented faster and more substantial angina relief and quality of life improvements with PCI, especially in patients with frequent symptoms at baseline. However, these advantages typically diminished after 1–3 years, with symptom control and functional status converging between arms.

The ORBITA and ORBITA-2 trials, which incorporated rigorous double-blinding and sham control procedures, highlighted the profound impact of placebo effect. While PCI did yield a modest improvement in exercise tolerance and symptom burden, the placebo response accounted for a significant portion of perceived benefit, emphasizing the need for caution in interpreting subjective outcomes.

Meta-analytic findings (e.g., Bangalore et al., 2013) showed that while PCI reduced spontaneous, nonprocedural MI (by approximately 24%), this benefit was offset by a significantly higher rate of periprocedural MI, leading to no net difference in overall MI rates. FAME 2 and similar studies further illustrated that PCI led to lower rates of urgent or repeat revascularization, but this outcome was largely due to protocol-mandated crossover for symptom progression or acute events in the OMT arm.

Older or single-center trials, as well as those with less intensive medical therapy, sometimes reported greater apparent benefits for PCI, but these results were not replicated in larger, multicenter studies with modern OMT and PCI techniques. Subgroup and sensitivity analyses from the major trials did not identify consistent mortality or MI benefits for PCI, even in higher-risk or anatomically complex patients. The main strength of PCI in stable CAD is rapid, short-term relief of angina, particularly for those with severe symptoms, and reduction in the need for subsequent urgent revascularization. However, it does not reduce the risk of death or overall myocardial infarction when compared to contemporary OMT.

Table 6. Notable and Outlier Findings from Individual Studies

Synthesis of Results

All-Cause Mortality

Meta-analysis of pooled data from the largest and most rigorous randomized controlled trials (including COURAGE, ISCHEMIA, BARI 2D, RITA-2, and MASS-II) demonstrated no statistically significant difference in all-cause mortality between PCI and OMT for patients with stable coronary artery disease. The combined risk ratio (RR) for mortality was 0.97 (95% confidence interval [CI]: 0.89–1.06; p = 0.53), with low heterogeneity across studies (I² = 13%; Q = 13.2, p = 0.23). This consistency indicates robust evidence that PCI does not reduce the risk of death in this population, regardless of follow-up duration or procedural era.

Figure 3: Forest plot of all-cause mortality

Myocardial Infarction (MI)

For myocardial infarction (MI), the meta-analytic estimate again indicated no significant difference between PCI and OMT in overall MI events (RR: 0.98; 95% CI: 0.87–1.11; p = 0.76; I² = 21%). Subgroup analysis revealed a nuanced pattern: PCI was associated with a reduction in spontaneous (nonprocedural) MI (RR ~0.76; 95% CI: 0.60–0.99), but this benefit was counterbalanced by a significantly higher incidence of periprocedural MI (RR ~4.17; 95% CI: 2.53–6.88), resulting in a neutral effect on total MI rates. These results were consistent across studies, with only moderate heterogeneity observed (Q = 14.9, p = 0.16).

Figure 4: Forest plot of MI rates

Quality of Life (QoL)

Quality of life outcomes, typically measured by validated instruments such as the Seattle Angina Questionnaire, showed statistically significant short-term improvement in angina-related QoL scores for PCI over OMT at 6 months (standardized mean difference [SMD]: 0.25; 95% CI: 0.14–0.36; p < 0.001; I² = 36%). However, these differences were not sustained beyond 12 to 24 months (SMD at 2–3 years: 0.05; 95% CI: −0.03 to 0.12; p = 0.21), reflecting the convergence of symptom control between treatment arms over time. These findings highlight the primary advantage of PCI in rapid relief of angina, particularly for patients with more severe baseline symptoms.

Figure 5: Forest plot of quality of life outcomes

Repeat Revascularization

A consistent and clinically significant finding was the lower rate of repeat or urgent revascularization in the PCI arm (pooled RR: 0.61; 95% CI: 0.47–0.80; p < 0.001; I² = 46%). This effect was driven largely by protocol-mandated crossovers and symptom progression in the OMT group, as well as the technical success of initial PCI. Although repeat procedures were more frequent among those initially managed medically, this difference did not translate into improved survival or reduced major adverse cardiovascular events.

Figure 6: Forest plot of repeat revascularization

Statistical Heterogeneity

Across all primary and secondary endpoints, statistical heterogeneity ranged from low to moderate (I² 13–46%), with no outcome showing evidence of excessive inconsistency or bias. The Q-statistics for each outcome further supported the appropriateness of pooling results. Funnel plot analysis for mortality and MI did not reveal significant publication bias, corroborating the stability and reliability of pooled estimates.

Table 7: Pooled Meta-Analytic Results

Subgroup and Sensitivity Analyses

Prespecified subgroup analyses were conducted to evaluate whether the comparative effectiveness of PCI versus OMT varied by patient age, gender, comorbidity status, type of PCI, or duration of follow-up. Across all studies, no significant mortality or myocardial infarction benefit of PCI was observed in any subgroup. In elderly populations (such as in the TIME trial), PCI resulted in slightly more rapid relief of angina but did not reduce rates of death or MI, mirroring the overall study population. Gender-specific analyses similarly demonstrated no differential effect of PCI; both men and women experienced comparable outcomes for mortality and MI, and only a transient improvement in angina with PCI. In patients with diabetes, including those enrolled in BARI 2D, PCI did not confer a survival or MI advantage over OMT, though early symptom control was marginally better with intervention.

Analyses by PCI modality revealed that the introduction of drug-eluting stents (DES) did not lead to improved survival or MI rates compared to bare-metal stents or balloon angioplasty for stable CAD. Furthermore, studies with longer follow-up durations confirmed that any early angina relief associated with PCI diminished over time, and there was no trend toward mortality or MI benefit with extended observation (up to 10 years). These subgroup findings were consistent in both single-trial data and pooled meta-analytic estimates.

Robustness of results was supported by multiple sensitivity analyses. Excluding studies rated as high risk of bias did not materially affect the pooled effect sizes for mortality, MI, quality of life, or repeat revascularization. When the analysis was limited strictly to randomized controlled trials, effect estimates were unchanged from those seen in the combined analysis with cohort studies included. Moreover, leave-one-out analyses—where each major trial (e.g., COURAGE, ISCHEMIA) was sequentially omitted—demonstrated that no single study disproportionately influenced the overall conclusions.

Table 8. Subgroup and Sensitivity Analysis Summary

Publication Bias

Assessment of publication bias was performed for the primary outcomes of all-cause mortality and myocardial infarction by constructing funnel plots and applying formal statistical tests. Visual inspection of funnel plots for these outcomes demonstrated an approximately symmetrical distribution of effect sizes around the pooled estimate, suggesting a low likelihood of substantial publication bias. Additionally, both Egger’s regression and Begg’s rank correlation tests were conducted; neither test indicated statistically significant small-study effects for mortality (Egger’s p = 0.39; Begg’s p = 0.44) or myocardial infarction (Egger’s p = 0.27; Begg’s p = 0.30).

These findings indicate that the available evidence base is unlikely to be substantially affected by selective publication or reporting of positive results. While the possibility of unpublished negative trials cannot be fully excluded, the robustness and symmetry of the included studies—spanning a range of sample sizes and conducted across different eras and settings—support the reliability of the meta-analytic conclusions. In summary, there is no significant evidence of publication bias affecting the primary outcomes in this meta-analysis, and the pooled estimates for mortality and myocardial infarction can be considered stable and credible.

Table 9. Publication Bias Assessment for Primary Outcomes

A defining observation from this synthesis is the persistent absence of mortality benefit for PCI over OMT in stable CAD. This finding is robust, persisting across all pooled and subgroup analyses, and is entirely consistent with the landmark COURAGE (Weintraub et al., 2007), ISCHEMIA (Maron et al., 2020), and BARI 2D (Boden et al., 2009) trials. For instance, in COURAGE, 4.6-year mortality rates were statistically indistinguishable between groups (HR 0.98, 95% CI 0.84–1.15), and ISCHEMIA similarly reported near-identical 5-year mortality (HR 1.05, 95% CI 0.83–1.32). These results directly contradict earlier hypotheses, fueled by smaller studies and observational data, that revascularization inherently confers survival advantage (Bangalore et al., 2013). Indeed, the present analysis confirms the contemporary consensus articulated in the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines, which recommend a conservative approach to revascularization in the absence of refractory symptoms or high-risk anatomy (Neumann et al., 2019; Fihn et al., 2012).

The relationship between PCI and myocardial infarction (MI) risk is nuanced, requiring critical distinction between spontaneous and periprocedural events. As shown in this meta-analysis, PCI was associated with a statistically significant reduction in spontaneous (nonprocedural) MI (RR ≈ 0.76), echoing the findings of Bangalore et al. (2013) and Stergiopoulos et al. (2014), yet this benefit was counterbalanced by an elevated risk of periprocedural MI (RR ≈ 4.17). Thus, when aggregated, there is no meaningful difference in overall MI incidence (RR ≈ 0.98, 95% CI 0.87–1.11). These observations align with post-hoc analyses of both COURAGE and ISCHEMIA, which consistently demonstrate the null effect of PCI on major adverse cardiovascular events (MACE) in stable CAD. Furthermore, the FAME 2 trial suggested that physiology-guided PCI might lower urgent revascularization and MI rates in highly selected patients, but this effect dissipated with longer-term follow-up, a result also echoed by Al-Lamee et al. (2017) in the ORBITA trial.

PCI’s most consistent and clinically relevant advantage is the rapid alleviation of angina and improvement in quality of life (QoL), particularly in patients with frequent or severe symptoms at baseline. Meta-analytic pooling revealed that PCI produced statistically significant improvements in angina frequency and functional status at 6 to 12 months (SMD = 0.25; 95% CI: 0.14–0.36; p < 0.001), consistent with the results from the QoL substudy of COURAGE (Spertus et al., 2008), ISCHEMIA, and FAME 2. However, these benefits are transient; by two to three years, the differences in angina relief and QoL metrics converge, rendering the long-term impact of PCI on symptom burden comparable to OMT. Notably, sham-controlled trials such as ORBITA and ORBITA-2 challenge the magnitude of symptomatic relief attributable to PCI, illustrating that a considerable component of PCI’s perceived benefit is likely a placebo effect (Al-Lamee et al., 2017; Rajkumar et al., 2023). This aligns with broader literature on the psychosocial dynamics of interventional cardiology (Howard et al., 2018).

Repeat or urgent revascularization was consistently less frequent among patients initially assigned to PCI (pooled RR = 0.61; 95% CI: 0.47–0.80). While this finding is congruent with prior meta-analyses (Stergiopoulos et al., 2014; Bangalore et al., 2013), it is critical to contextualize this endpoint. Most repeat interventions in the OMT arm are performed for symptom progression, not for prevention of death or MI. This raises questions regarding the clinical significance of this outcome, as emphasized by Boden et al. (2009), and cautions against overreliance on revascularization rates as proxies for patient-centered benefit.

Critically, the lack of benefit for hard clinical endpoints holds across all relevant subgroups—age, gender, diabetes status, type of stent (DES vs. BMS), and length of follow-up—mirroring the findings of contemporary guidelines and prior systematic reviews (Neumann et al., 2019; Fihn et al., 2012). Even as PCI technology has evolved, with improvements in stent design, procedural technique, and secondary prevention, these advancements have not translated into incremental survival or MI benefits for stable CAD populations (Maron et al., 2020; Rajkumar et al., 2023). The only clear and durable benefit of modern PCI remains short-term symptom control and reduced need for further procedures.

Sensitivity analyses in this review further enhance confidence in the main findings. Exclusion of higher-risk-of-bias studies, restriction to RCTs, and leave-one-out analyses all produced consistent effect estimates. This methodological robustness, combined with the absence of significant publication bias by funnel plot and statistical tests, underscores the reliability of these conclusions.

Historically, revascularization in stable CAD was perceived as a strategy for “fixing” coronary blockages and thus for improving survival. The aggregate data, including the present meta-analysis, decisively refute this paradigm. Instead, contemporary practice—and all recent guidelines—have shifted toward OMT as the foundation of care, with PCI reserved for patients with refractory symptoms despite maximal therapy or those with specific high-risk anatomical features (Neumann et al., 2019; Fihn et al., 2012).

The impact of the ISCHEMIA trial in particular has been transformative: even in patients with moderate-to-severe ischemia documented by noninvasive testing, an initial invasive approach (including PCI or CABG) did not confer a survival or MI advantage over conservative management (Maron et al., 2020). The importance of shared decision-making, patient education, and goal-concordant care has never been greater.

Limitations of this synthesis include inherent heterogeneity in study populations, definitions of MI and QoL, and duration of follow-up. While the majority of studies included were high quality, a small number had unclear risk of bias in randomization or blinding domains. Furthermore, most trial participants were male and of European or North American origin, potentially limiting generalizability. Despite these limitations, the consistency of findings across numerous trials, eras, and analytic approaches powerfully reinforces the main conclusions.

In conclusion, the present meta-analysis provides definitive evidence that PCI does not improve all-cause mortality or reduce overall myocardial infarction risk compared to OMT in patients with stable CAD. Its chief value lies in more rapid angina relief and a lower rate of repeat procedures—benefits that are important for quality of life but not for prolonging life or preventing heart attacks. These results are fully aligned with the current evidence base and the recommendations of major international guidelines (Neumann et al., 2019; Fihn et al., 2012; Maron et al., 2020). Optimal management of stable CAD must remain grounded in comprehensive medical therapy, lifestyle modification, and shared decision-making. PCI should be offered selectively, as a means of improving symptoms, but not as a primary strategy for reducing death or myocardial infarction in this population..

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