After 4 whole decades of thinking that invasive treatment (stenting or bypass surgery) for a local block in an artery due to cardiovascular (CV) disease could extend life and preserve heart health in patients who also had advanced kidney disease, the world just turned upside down.
The results of the ISCHEMIA trial, reported at the American Heart Association’s scientific sessions (2019) show that the conservative management of patients with cardiovascular disease and chronic kidney disease is just as good as highly invasive – and very expensive – methods of treatment, such as cardiac bypass. In other words, treat the disease, not the sign of disease – in this case, the blocked blood vessel.
Credit: Brian A Jackson / Shutterstock
Atherosclerosis, or hardening of the arteries, is the biggest risk factor underlying CV disease. It is a systemic illness caused by inflammatory processes in the blood vessel wall. These in turn are due to high levels of lipids belonging to the LDL, VLDL, and triglyceride category, which induce changes in the smooth endothelial lining, creep between and under the endothelial cells, and eventually cause a fatty streak. This then undergoes calcification and/or slow enlargement, protrudes into the space inside the vessel, to narrow or even completely block the vessel. The large plaque, as it is now called, may also ulcerate over it surface, causing the blood in contact with its surface to clot. The clot may break off in bits, and the fragments zoom along the circulation to lodge in various smaller blood vessels. This obstructs blood flow to the organs supplied, such as the heart with coronary artery blockage, and the brain with carotid artery blockage.
Chronic kidney disease
The current trial looked at the outcomes of medical vs invasive therapy in patients with chronic kidney disease because this number is rapidly growing, due to the increase in obesity and diabetes rates. Moreover, few such patients have been included in previous trials of conservative vs invasive management of heart disease, such as the COURAGE, FAME and BARI 2D.
The trial looked at 777 patients with chronic severe kidney disease and stable moderate or severe ischemic CV disease. Half of these patients were on dialysis.
After randomizing the patients, those in the invasive arm had angiography followed by bypass or percutaneous coronary intervention (PCI). With a bypass, lengths of healthy veins are taken from another part of the patient’s body to replace blocked segments of the coronary arteries. With PCI, a balloon is used inside the blocked arteries to inflate the segment, and a stent is introduced to keep the artery patent until it heals. The surgery was followed by optimal medical treatment.
The other arm was given only appropriate medical treatment, but any patient who required invasive procedures received them.
The final outcomes showed that angiography was done in 85% of patients in the invasive arm followed by revascularization procedures in 50%, mostly by PCI. In the medical arm, 22% had angiography and 12% invasive treatment.
The scientists compared the risk of 5 outcomes related to cardiovascular health in both groups. The outcomes included myocardial infarction (MI, or heart attack), cardiovascular death (CV death), rates of hospitalization for unstable angina, hospitalization for heart failure, and cardiac arrest. There was no significant difference in the composite outcome - whether or not an initial angiography was done, followed by invasive surgery – or the patient was managed with optimal medical treatment alone. The probability that death from all causes would be reduced by even 10% following revascularization procedures was even lower than 10%, say the researchers.
For instance, the mortality or heart attack rate was approximately 36% with surgery and about 38% with medical therapy alone, in patients with stable coronary heart disease and coexisting chronic kidney disease. Individual endpoints also did not vary, nor the overall quality of life. This lack of benefit was consistently seen for all outcomes, with invasive treatment in a variety of settings. The risk for occurrence of new stroke was increased by 376%, in fact, following surgical management compared to medical management. The risk of death or a new dialysis case was also increased by 48% in the invasive treatment arm. The reason for the increased risk needs to be clarified, as it may not be related to the procedure, but is perhaps because the patients are sicker.
For patients with severe ischemia, analysis suggests that invasive treatment could be better, but for others, medical treatment is probably all that is required.
The trial changes a lot of medical thinking about coronary heart disease patients with a low level of symptoms, in short, and could transform the way cardiology is practiced today. It comes as a strong support to many smaller and weaker trials showing the same trend. Cardiologist Kim Eagle comments, “It's going to be hard in patients that are not unstable on best medical therapy to show benefit of revascularization when we're able to control the risk factors as well.”
The key point to take away is that physicians need to keep in mind the importance of treating the disease itself, by several crucial and targeted interventions – a more active lifestyle, less fatty food, a lower total carbohydrate intake, less stress, quit smoking and excessive drinking, as well as medications.
The researchers found that when these interventions were in place, even without surgical support, over 95% of older patients continued to enjoy good health after 3 years or more even though they already had CVD of significant degree at the start of the trial.
In short, getting a blockage is not an automatic death sentence. Switching to a healthy lifestyle, combined with appropriate medication, and removing risk factors such as smoking, is a much better way to live longer with stable CV disease. In case patients fail to respond to this treatment, invasive treatments may be considered in patients who fail to respond to medical therapy – who are a minority.
Of course, classical cardiologists disagree, pointing out that the trial had a defined population without known illnesses or factors that are used to identify those who will benefit from re-establishing circulation through blocked vessels. In this respect, it does not resemble a direct comparison of invasive vs medical therapy.
The researchers have focused, however, on the large population of stable patients with coronary disease for whom invasive procedures are recommended. Symptom relief in the small patient population with a high symptom level, or in those who have had a cardiac arrest or heart attack, for instance, remains to be assessed.
The findings of the trial deserve wide publicity so that they can influence and change clinical cardiology practice the world over. They also highlight the importance of running randomized clinical trial on new therapies before they firm up into accepted practice – when they are extremely hard to change. Defending the $100 million cost of the meticulously designed and executed trial, researcher Judith Hochman says, “We calculate that if asymptomatic patients didn't get PCI we would save over $500 million dollars every year.”
International Study of Comparative Health Effectiveness With Medical and Invasive Approaches–Chronic Kidney Disease - ISCHEMIA-CKD - https://www.acc.org/latest-in-cardiology/clinical-trials/2019/11/16/14/48/ischemia-ckd