One of the reasons this newsletter is late is that I was anxious to report on the funeral ceremony of Senator John McCain held at the majestic National Cathedral in Washington, DC, on Saturday, September 1.  Designed by Mr. McCain himself, it was his last great contribution to our nation.  In attendance, by personal invitation, was a broad cross section of great Americans, including presidents George W. Bush, Barack Obama, and Bill Clinton, their first ladies, Laura, Michelle, and Hillary, former vice president, Joseph Biden, and former senators Bob Dole, also a wounded-in-action veteran, and his wife, Elizabeth, former secretary of state, John Kerry, and the current governor of Ohio and future president, John Kasich. Among those eulogizing the Senator were his daughter, Meghan, George Bush, Barack Obama, one of the three "amigos," former Senator Joseph Lieberman, and former secretary of state, Henry Kissinger.  All spoke of his warrior spirit and passionate dedication to the principles that have made America great, especially his absolute faith in "All men are created equal," how he despised despots and bullies, and his conviction that compromise was the key to solving problems.  As the Glee Club from the US Naval Academy sang a spirited rendition of the Battle Hymn of the Republic and Renee Fleming sang "Oh Danny Boy," tears welled up in Mrs. McCain's eyes and mine.  The scripture readings were so appropriate, especially this one from the Book of Wisdom 3:1-9, for a a naval airman who had suffered in the "Hanoi Hilton" for six years, several of them in solitary confinement, where he was tortured and brutalized:  "For if before men, indeed they be punished, yet is their hope full of immortality; chastised a little, they shall be greatly blessed, because God tried them and found them worthy of himself."   Father Edward Reese, SJ, former president of Brophy College Preparatory School in Phoenix, where McCain's navy sons, Jack and Jimmy attended high school, alluded to the senators passion for justice by quoting a poem by Gerard Manley Hopkins, SJ, entitled "As Kingfishers Catch Fire."  The poem says "The just man justices..."  Indeed!!

In the broadway musical, "Hamilton," the character George Washington, says, "Dying is easy, living is harder."  Life was hard for John McCain and he made the most of it.  Defeated in battle and in his bid to become president, he rose to the House and six terms in the Senate.  His hero was Robert Jordan, the American volunteer in Hemingway's novel,  "For Whom the Bell Tolls," who dies in a rear guard action at the hands of fascists during the Spanish Civil War. Like Jordan, McCain was a warrior who was willing to risk and sacrifice self for a cause greater than himself.  His funeral and the life it celebrated were a resounding rebuke to the partisan politics and mean spiritedness that have unfortunately gripped our country. God Bless You, John McCain!  Indeed, He already has and everyone of us who admire this authentic American Hero!

The results of two large aspirin primary prevention trials were published on August 26.  The first, known as ARRIVE, was published in THE LANCET, and the second, known as ASCEND, was published online in the New England Journal of Medicine.

Before I discuss the results, it is critical that patients understand the difference between primary and secondary prevention.  Primary prevention means you never had a cardiovascular event such as a heart attack (MI), angina, transient ischemic attack (TIA), stroke (CVA), stent, carotid plaque, peripheral vascular disease or vascular calcification.  Secondary prevention means you have one or more of these.  The importance of low dose (81-100 mg) aspirin in secondary prevention is well established and non-controversial. Aspirin inhibits aggregation of the platelets that clog vital arteries during a heart attack or stroke and is an essential medicine in patients with known cardiovascular disease unless there is a strong contraindication such as active GI bleeding.

The use of aspirin in primary prevention, on the other hand, is nuanced.  ARRIVE was conducted between July 2007 and November 2016 and enrolled 12,000 patients in seven countries at more than 500 study sites.  For the primary endpoint--time to first occurrence of cardiovascular death, myocardial infarction (heart attack/MI), unstable angina, stroke, or transient ischemic attack (TIA)--there was no significant difference between the groups assigned to aspirin versus placebo.  Overall rates of gastrointestinal bleeding were low, less than 1%, but twice as high in the aspirin group than in the placebo group, a statistically significant difference. If one stops here, you might conclude that taking aspirin for primary prevention is not a good idea.  But now comes the big AH HAH finding: among patient who actually took aspirin compared to those who did not, aspirin was associated with a 47% decreased risk of first MI, a major benefit.

As summarized on the American College of Cardiology (ACC) web site, the second study, ASCEND, compared outcomes in 15,480 diabetic patients forty years of age or older, with no known cardiovascular disease, making this a primary prevention trial.  Half received 100 mg of aspirin daily while the other half received placebo.  The median duration of follow-up was 7.4 years.  The primary efficacy outcome ( vascular death, myocardial infarction, or stroke/transient ischemic attack) occurred in 8.5% of the aspirin group compared with 9.6% of the placebo, a 12% reduction.  The primary safety outcome ( intracranial bleeding, gastrointestinal hemorrhage, or sight-threatening eye bleeding) occurred in 4.1% of the aspirin group compared with 3.2% of the placebo group, a 29% relative increase in major bleeding events compared with placebo, mainly due to GI hemorrhage.  The authors conclude that the benefit of aspirin was largely negated by excess bleeding. The ACC concluded, "the use of aspirin among diabetics with no known cardiovascular disease needs to be individualized."

The USPSTF has modified its guidance in light of these and other aspirin primary prevention trials as follows:

In adults aged 50-59 years of age with a 10-year cardiovascular risk greater than or equal to 10%, USPSTF recommends initiating low-dose aspirin for the primary prevention of cardiovascular disease and colorectal cancer in patients who are not at increased risk of bleeding, have a life expectancy of at least ten years, and are willing to take low-dose aspirin daily for at least 10 years.

In adults aged 60-69 years of age with a 10-year cardiovascular risk greater than or equal to 10%, USPSTF recommends initiating low dose aspirin for the primary prevention of cardiovascular disease and colorectal cancer in patients who are not at increased risk of bleeding, have a life expectancy of at least 10 years, and are willing to take low dose aspirin for at least ten years.

The USPSTF says data are insufficient in adults younger than 50 years of age and adults 70 and older.

The heart risk calculator used by the USPSTF can be found at  cvriskcalculator.com.  Calculate your 10-year heart risk today to help decide if you should take aspirin for primary prevention!

MY TAKE: I would rather treat a GI bleed, nose bleed, and/or bruising than a heart attack or stroke any day of the week!  Most bleeding, especially GI bleeding, is usually easily managed and patients recover completely.  Heart Attack and Stroke, on the other hand, can be fatal, and often have long lasting life-altering effects that cannot be reversed.  Keep this in mind when you are deciding whether to take a daily low dose aspirin for primary prevention. Following the advice of the USPSTF, I take one everyday.

As reported in the New England Journal of Medicine on August 26, among patients with diabetes without evidence of cardiovascular disease (primary prevention), there was no significant difference in the rate of serious vascular events between those who were assigned to receive n-3 fatty acid supplementation as compared to those who received placebo.