SERMO Cardiologists will be covering the 2016 American College of Cardiology Scientific Sessions. We’ll be sharing some of their posts here on the SERMO blog – for more coverage, sign into SERMO.
American College of Cardiology 2016, Chicago. Salim Yusuf, McMaster University and collegues presented the Data on the HOPE – 3 trial . (Effects of Combined Lipid and BP-Lowering on Cardiovascular Disease in a Moderate Risk Global Primary Prevention Population) The bottow line was that Resuvastatin + Candasartan/Hctz at low doses improved morbidity and mortality most in hypertensive pateints but also in those with boarderline hypertension, irregardless of their LDL. Only resuvastatin helped if your blood pressure was normal.
I braved an unusual April snow storm in cold chicago to bring you this update! The Hope trials are a Series of 2 x 2 factorial trials that have been Run by Dr. Yousef from Canada for a number of years. You may remember the early trials showed that taking vitamin E is worthless, and that taking Ramapril helps prevent death and MI in patients who even have normal starting blood pressure.
This trial showed that Lowering cholesterol with statins significantly reduced adverse cardiovascular events in people with average cholesterol and blood pressure levels. They enrolled patients all their patients outside of the USA and showed that in these intermediate cardiovas risk for heart disease benefitted from blood pressure-lowering medications, only if they had higher blood pressure levels! ( Surprise). They also showed taking resuvastatin benefitted all these patients at intermediate cardiovascular risk, regardless of their LDL.
Previous studies have focused on the impacts of cholesterol and blood pressure-lowering drugs for people with high cholesterol, high CRP, Hypertension, renal disease, or other high risk conditions. This trial, HOPE-3, looked at outcomes of preventative treatment with cholesterol and blood pressure-lowering drugs in a large intermediate CV risk population. .
The HOPE -3 Trial included12,705 people in 21 countries ( but not the USA). All participants had at least one known cardiovascular risk factor: dyslipidemia, smoking, an elevated waist-to-hip ratio, family history of heart disease, but none had been diagnosed with cardiovascular disease. The trial was designed to focus on preventing cardiovascular disease before it starts. The trial enrolled men over 55 and women over 60, with 46% of particpants being women. No strict blood pressure or LDL criteria for enrollement. It was a 2 x 2 factorial trial with four groups: placebo, Resuvastatin 10 mg, Candesartan 16mg/Hctz 12.5, or both Resuvastatin and Candesartan.
At enrollment the blood pressure was average 128/82 with LDL 128. 87% of patients had an elevated waist to hip ratio ( they were fat). In just looking at blood pressure lowering. The average blood lowering was 6 mmHg systolic and 3 mm diastolic for the 16 mg Candesartan +12.5 mg Hydrochlorotiazide. Outcomes were tracked for a median of 5.6 years.
It is no surprise to learn that taking the Antihypertensive, benefitted the patients who had hypertension. In the total trial, fixed dose Candesartan/HCTZ did not reach statistical significance. But if your blood pressure was over 143 mmHG, there was a very beneficial effect in reducing morbidity and mortality by taking anti hypertensive alone.
10 mg resuvastatin lowered LDL an average of 34.6 mg/dl and decreased Death, MI and stroke in all the patients who recieved it. (We knew that Statins worked over 15 years ago.) What this trial showed was that there was an additive benefit to taking the Resuvastain and Candesartan/hctz. The patients who benefitted most were those with Hypertension. There was a 45% redicution in MI for the combo therapy. Most of the Effect was from the Resuvastatin In low blood pressure patients it was the Resuvastatin alone that gave a benefit.
Cardiovasculardeath, heart attack or stroke occurred in 3.5 percent of patients receiving both drugs and in 5 percent of patients receiving only placebo.
The benefits of statins were similar in all ethnic groups, and regardless of the baseline LDL levels. This extends our knowledge from the Jupiter trial, and suggesting that a person’s starting cholesterol levels are not important in determining whether the person will benefit from statins. These findings suggest that many people who have average cholesterol and blood pressure levels and are at average risk for heart disease—and not just those with extremely high cholesterol or blood pressure levels—can benefit from statins. The treatment was also remarkably safe; although some patients reported muscle weakness or pain,these effects were generally alleviated by stopping the statins or reducing the dose.
This Trial teaches us that our hypertensive patients have systemic vascular disease irregardless of their cholesterol numbers. The lead investigator, Dr. Salim Yousef Said, “Most of hypertension guidelines right now focus on what agents to use and what blood pressure to aim for, and there has been very little emphasis on the importance of statins in treating patients with hypertension, Our approach, which used a combination of moderate doses of two blood pressure lowering-drugs plusa statin,appears to producethe biggest ‘bang,’interms of reducing events,with few side effects.”
The trial did not show a benefit to given Candesartan/HCTZ to patients with normal cholesterol. In discussing the “poly pill” concept, Dr. yousef stated, “there may be more than one poly pill necessary. One for the diabetic and one for the hypertensive.” “This trial is a baby step in the creation of the poly pill.” During the question and answer, it was noted that use of aspirin was not invesitgated and that it’s use may have effected the endpoint of death, MI and stroke.
It was noted that this trial used simple identifiable risk factors, and showed that there is benifit from a simple treatment. The patients were brought back for follow up each 6 months during the 5 years of the trial and did not have a lot of complications from the therapy. One limitation of the study is that, while it tracked patients for more than five years, that is not a long time. Participants will be tracked for an additional three to five years. The researchers will continue to conduct additional analyses examining the effects oncognitive decline, erectile dysfunction and vision.
Upon presentation of this Trial – three papers were published concurrently in the online NEJM on April 2, 2016.