Now comes a new large randomized study by Mc Neil, et al, conducted in healthy adults aged 70 or older and published online in three parts in the New England Journal of Medicine on September 16.  Keep in mind that this was a primary prevention trial, meaning that the subjects had not suffered a heart attack, stroke, or TIA and had no prior history of coronary stents, diabetes, or peripheral vascular disease.  

The study enrolled community dwelling persons in Australia and the United States who did not have cardiovascular disease, dementia, or disability.  Participants were randomly assigned to receive 100 mg of aspirin or placebo. In the first part of the study, higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death, a big and disappointing surprise!

In the second part of the study, the authors tested how many patients treated with low dose aspirin or placebo suffered a major hemorrhage and how many went on to develop cardiovascular disease defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure.  Surprisingly and disappointingly, the use of low-dose aspirin resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo.

The third part of the study showed that low dose aspirin, as compared to placebo, did not reduce the likelihood of death, dementia, or persistent physical disability.

As discussed in previous newsletters, immunotherapy is having a major impact on the treatment of cancer.  Tumor cells express a molecule known as PD-L1 (programmed death ligand 1) which inactivates would-be killer T lymphocytes.  Monoclonal antibodies that block this interaction restore T cell function so they can kill cancer cells more effectively. 

Three new studies have now been published online in the New England Journal of Medicine on September 26 showing how such antibodies can be helpful in the treatment of lung cancer, the most common fatal cancer in the United States.

In the first study by Paz-Ares, et al.,  patients with previously untreated metastatic squamous Non Small Cell Lung Cancer (NSCLC) with at least 50 percent of the tumor cells expressing PD-L1 were randomized to chemotherapy alone or chemotherapy supplemented with an anti-PD-L1 monoclonal antibody known as pembrolizumab® .  The median overall survival was 15.9 months in the combination group versus 11.3 months in the chemotherapy alone group, a modest but highly statistically significant difference.

The second study, conducted by Horn, et al., was similar in design and compared another anti-PD-L1 monoclonal antibody, atezolizumab® in combination with chemotherapy to chemotherapy alone in patients with extensive Small Cell Lung Cancer (SCLC), a much less common and more aggressive form of lung cancer.  The median overall survival was 12.3 months in the combination group versus 10.3 months in the chemotherapy alone group, a modest but highly statistically significant difference.

In the third and most important of the three studies, patients with stage III, unresectable non-small cell lung cancer (NSCLC) who were previously stable after treatment with radiation and chemotherapy (" chemoradiotherapy") were randomized to receive yet another anti-PD-L1 monoclonal antibody known as durvalumab® or placebo.  The 24-month survival was 66.3 percent in the durvalu mab ®  group, as compared with 55.6 percent in the placebo group.  Median progression free survival was 17.2 months in the durvalumab ®  group and 5.6 months in the placebo group.  The median time to death or distant metastasis was 28.3 months in the durvalumab ®  group and 16.2 months in the placebo group. 15.4 per cent and 9.8 percent of patients discontinued the trial regimen because of adverse side effects in the treatment and placebo groups, respectively.

For cancers that have largely defied medical therapy, these are encouraging results and demonstrate, yet again, that combining modalities is the best way to tame and ultimately defeat cancer.  Living with cancer has become a reality.  We owe a debt of gratitude to the patients who agreed to participate in these important trials, not knowing if they would be in the treatment or placebo arms of the trial.

Severe valvular heart disease is usually treated surgically but not all patients with severe valvular heart disease are healthy enough to undergo open heart surgery.  Bioengineers, working closely with cardiologists and surgeons, have therefore devised technologies to repair valves using catheters.  The best current example is known as TAVR which stands for Transcatheter Aortic Valve Replacement.  In TAVR, a collapsed stent carrying a pig aortic valve is placed across the patient's stenotic aortic valve with a  catheter and then abruptly opened, thereby replacing the patient's aortic valve with a pig valve in a single deployment.  This technique is now practiced at Jersey Shore University Medical Center and other major cardiac centers and has enjoyed considerable success.

Now comes catheter technology to repair leaky mitral valves in patients where dilatation of the left ventricle pulls the anterior and posterior leaflets of the mitral valve apart ("secondary mitral regurgitation").  Using catheters, a clip is placed across the mitral leaflets creating a double orifice valve.  As published online in the New England Journal of Medicine on September 23 by Stone, et al., of Columbia University Medical Center, in patients with heart failure and moderate to severe mitral regurgitation who remained symptomatic despite the use of maximal doses of guide-line directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization (35.8 percent vs. 67.9 per cent) and lower all-cause mortality  (29.1 per cent vs. 46.1 percent) after 24 months as compared to medical therapy alone.  The complication rate was low.