Acute Coronary Syndromes in Cancer Patients

During the last two decades, there has been a tremendous increase in cancer survival.1 As a result, the number of patients with a current or prior cancer presenting for cardiovascular care has dramatically risen.1,2 In fact, patients with a cancer diagnosis face almost twice the risk of developing an acute coronary syndrome (ACS) or other cardiovascular disease event compared to the general population.3 Recent observational data highlighted the 6-month cumulative incidence of myocardial infarction to be 2.0% among cancer patients, compared to 0.7% in age-matched cancer-free controls.4 Furthermore, just as in the general population, the majority of myocardial infarctions in cancer patients occur as non-ST elevation myocardial infarctions (NSTEMI). However, in contrast, mortality over time among all cancer patients with NSTEMI appears higher in the presence of cancer compared to the general population.5,6 The presentation of ACS is usually atypical in cancer patients, with less than one-third of cancer patients presenting with chest pain, and less than half experiencing dyspnoea, suggesting the need of higher clinical suspicion.5 Diagnosis of ACS in cancer is based on the clinical history of the patient, prior risk factors, electrocardiogram findings as well as evaluation of cardiac biomarkers over time; additionally, cardiovascular imaging is implicated in certain cases.5 The causal relationship between ACS and cancer can partially be attributed to the modifiable and non-modifiable risk factors shared between these disease states.7 Cancer is associated with a pro-inflammatory and hypercoagulable profile with increased platelet activation and aggregability, which may contribute to the observed increase in the prevalence of ACS5,8 (Figure 1). Additionally, the recent proliferation of novel cancer therapies has led to significant improvement in cancer-related mortality, but unfortunately has also resulted in an increase of cardiovascular adverse events, including ischaemia, arrhythmias, and heart failure.9 Radiation therapy has also been implicated in the development of accelerated coronary artery disease, particularly among those with chest-field exposure (e.g. breast, lung, and lymphomas) (Figure 2). Moreover, available retrospective population-based data suggest potential coronary effects even within 5-years of treatment directly proportionate to cardiac radiation dose (7.4% per grey).5,10–12 However, the effects of contemporary cardiac-sparing techniques on this risk remain unknown.13 Finally, some of this excess risk of ACS in cancer may also be due to external factors such as the effects of stress, frequent interruption of anti-thrombotic treatment, and increased surveillance in cancer patients.5 Although the case fatality rate of ACS has been steadily declining over time due to improvement in prevention, diagnosis, and care of ACS patients, the 1-year mortality can still be as high as 10%.14 Similarly, over the past decade, although the cancer death rate has declined by about 2%, it still remains one of the top killers in the world.15 Therefore, preventing and managing elevated rates of ACS in cancer is noteworthy. Unfortunately, so far, randomized controlled trials and prospective studies assessing the efficacy and safety of ACS treatment have excluded cancer patients, thus current treatment guidelines cannot be easily applied to cancer patients. However, in cancer patients with acute ischaemia, a temporary cessation of anti-cancer therapy followed by administration of parenteral anticoagulation, nitrates, and calcium channel blockers is warranted.8 Optimal medical therapy in the form of statins, angiotensin-converting enzyme inhibitor, mineralocorticoid-receptor antagonist, and β-blockade has been the next logical step while treating ACS in cancer patients.8 In fact, optimal medical therapy was shown to reduce the rate of serious cardiovascular events by 32% at 1-year in cancer patients with ACS undergoing percutaneous coronary intervention (PCI).16 Revascularization with PCI or coronary artery bypass graft (CABG) should be carried out when indicated in a process of shared decision-making with the patient and after balancing its risks and benefits in addition to the patient’s disease prognosis and treatment preferences. However, in an observational cohort of patients with metastatic cancer, PCI did not seem to provide an additional benefit to optimal medical therapy at follow-up in the NSTEMI group as opposed to the STEMI group.6 These findings support the role of shared decision-making, patient preference, and cancer-prognosis, in the determination of the efficacy of non-emergent PCI. The use of antiplatelet agents in cancer patients needs to be closely supervised because of the adverse coagulation profile associated with cancer,8 especially since the occurrence of bleeding complications in patients with ACS is associated with higher in-hospital mortality.17 Thus, the decision whether to continue, or withdraw the antiplatelet therapy should be based on the severity of bleeding after balancing its risks and benefits in addition to the patient’s clinical status.17 In spite of an increased bleeding risk, a prior study reported lower in-hospital survival in thrombocytopenic cancer patients with ACS who did not receive aspirin compared to those who received the drug with 6% vs. 90%.18 As of now, the first-choice antiplatelet drugs in ACS patients with cancer are aspirin (300/75 mg) and clopidogrel (300–600/75 mg).17 Percutaneous revascularization is indicated in the majority of ACS patients with STEMI, and in a large number of moderate and high-risk NSTEMI/unstable angina.5 However, PCI in cancer patients depends on an intact haematopoietic system for safety and cancer patients undergoing PCI have been shown to be associated with increased complications such as increased in-hospital mortality (up to three times), stent thrombosis, and increased bleeding because of adverse cardiovascular effects of anti-cancer therapy as well as an adverse haematopoietic profile seen in cancer.5 In general, an invasive functional assessment of coronary stenosis with functional flow reserve is advised before undergoing PCI as highlighted in consensus statements.19 Moreover, in patients with cancer who experience ACS, PCI with bare metal stent implantation should be considered in instances when short-term dual antiplatelet therapy is needed; however, some cancer patients might benefit from prolonged dual antiplatelet therapy. Although both invasive treatment and optimal medical therapy are underused in cancer patients with ACS, a recent study highlighted that PCI is in fact common in cancer patients.20 However, data regarding PCI outcomes in cancer patients are limited. Some ACS and cancer patients with advanced coronary artery disease may need CABG for revascularization.17 The ideal time to undergo CABG (platelet count > 50 000/μL) should be within 2–6 weeks after ACS in clinically stable patients.17 The advantages of CABG over PCI include the lack of need for dual antiplatelet therapy and absence of stent thrombosis.17,21 However, radiation therapy in cancer patients undergoing CABG could impair healing of the surgical sternal incision as well as of the mediastinum complicating the actual surgical procedure, something not seen with PCI.17 Moreover, development of deep vein thrombosis, a risk for any surgical patient, but of more concern in the cancer patient is one more problem with CABG8,17 (Figure 3). Acute coronary syndrome represents an increasingly common, high-risk dilemma faced by cardiovascular providers. The rapid influx of novel anticancer therapies, and improved cancer survival have led to new cardiovascular-related challenges faced by healthcare providers. The current limited evidence from registries and observational studies suggest that ACS among cancer patients should be managed according to the recommended guidelines for general population patients. However, current evidence focused on specific cancer types, populations, or survivors to guide these recommendation remains limited. Since prognosis has considerably improved in many cancer patients in the last decade, patient-specific assessment of risk, accounting for disease prognosis, cancer therapy-type, and close communication with oncologic providers are vital to optimal outcomes. Finally, additional prospective studies specifically focused on defining optimal treatment strategies in cancer patients with ACS are needed. *Both authors contributed equally. Conflict of interest: none declared. References are available as supplementary material at European Heart Journal online.