The Trials Of Ms Americana.127
Yvette Burkhammer
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Background Whether marine omega-3 supplementation is associated with reduction in risk of cardiovascular disease (CVD) remains controversial. Methods and Results This meta-analysis included study-level data from 13 trials. The outcomes of interest included myocardial infarction, coronary heart disease (CHD) death, total CHD, total stroke, CVD death, total CVD, and major vascular events. The unadjusted rate ratios were calculated using a fixed-effect meta-analysis. A meta-regression was conducted to estimate the dose-response relationship between marine omega-3 dosage and risk of each prespecified outcome. During a mean treatment duration of 5.0 years, 3838 myocardial infarctions, 3008 CHD deaths, 8435 total CHD events, 2683 strokes, 5017 CVD deaths, 15 759 total CVD events, and 16 478 major vascular events were documented. In the analysis excluding REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), marine omega-3 supplementation was associated with significantly lower risk of myocardial infarction (rate ratio [RR] [95% CI]: 0.92 [0.86, 0.99]; P=0.020), CHD death (RR [95% CI]: 0.92 [0.86, 0.98]; P=0.014), total CHD (RR [95% CI]: 0.95 [0.91, 0.99]; P=0.008), CVD death (RR [95% CI]: 0.93 [0.88, 0.99]; P=0.013), and total CVD (RR [95% CI]: 0.97 [0.94, 0.99]; P=0.015). Inverse associations for all outcomes were strengthened after including REDUCE-IT while introducing statistically significant heterogeneity. Statistically significant linear dose-response relationships were found for total CVD and major vascular events in the analyses with and without including REDUCE-IT. Conclusions Marine omega-3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD, even after exclusion of REDUCE-IT. Risk reductions appeared to be linearly related to marine omega-3 dose.
Methods: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating β-blockers in myocardial infarction enrolling at least 100 patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion-era (> 50% undergoing reperfusion or receiving aspirin/statin) or pre-reperfusion-era trials.
Conclusions: In contemporary practice of treatment of myocardial infarction, β-blockers have no mortality benefit but reduce recurrent myocardial infarction and angina (short-term) at the expense of increase in heart failure, cardiogenic shock, and drug discontinuation. The guideline authors should reconsider the strength of recommendations for β-blockers post myocardial infarction.
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For decades, women have used hormone therapy to ease symptoms of menopause, such as hot flashes and sweating. This is called menopausal hormone therapy, and you may see it abbreviated as HT or MHT. You may also hear it described as hormone replacement therapy (HRT), postmenopausal hormone therapy (PHT), or postmenopausal hormones (PMH).
The ovaries stop releasing eggs and making the female hormones, estrogen and progesterone. In the months or years leading up to natural menopause, menstrual periods may become less frequent and irregular, and hormone levels may go up and down. This time is called perimenopause or the menopausal transition. Since periods can become less frequent during this time, it can be hard to know when they have actually stopped (and you have gone through menopause) until you look back at a later time.
There are also many progestins available, but medroxyprogesterone acetate (MPA or Provera), is often used with an estrogen to treat menopausal symptoms. Some preparations contain both an estrogen and a progestin.
Treating menopausal symptoms with estrogen and progestin together is known as estrogen-progestin therapy (EPT) or combined hormone therapy. Although estrogen alone improves the symptoms of menopause, it increases the risk of cancer of the uterus ( endometrial cancer). Adding a progestin to the estrogen lowers the risk of endometrial cancer back to normal. Because of this, EPT is given to women who still have a uterus (those who have not had a hysterectomy). EPT can be given 2 ways:
Systemic hormones can help with certain symptoms of menopause, such as hot flashes and night sweats, as well as problems linked to thinning of the lining of the vagina (such as dryness that can make sex painful). They can also help prevent and treat osteoporosis (severe bone thinning).
Hormones, most often estrogen, can also be placed in or near the place that needs treatment. This is called topical hormone therapy. If small doses are used, little of the hormone is absorbed into the bloodstream, so it has little if any effect on the rest of the body.
Many observational studies have looked at MHT and cancer risk. One example is the Million Women Study. It enrolled over a million women aged 50 to 64 in the UK, collected information about hormone use and other health and personal details, and followed the women for many years. Not all of the women in the Million Women Study took MHT. Some of the women taking MHT were on ET, some were on EPT, and some took another drug. Some of the women on ET still had their uterus.
Studies show that EPT does not increase the risk of endometrial cancer (cancer in the lining of the uterus). It is linked to a higher risk of abnormal vaginal bleeding. Because vaginal bleeding after menopause can be a symptom of endometrial cancer, this often leads to further testing.
Based on the WHI study, taking EPT is linked to a higher risk of breast cancer. The longer EPT is used, the higher the risk. The risk returns to that of a woman who never used EPT (the usual risk) within 3 years of stopping the hormones. Breast cancers in women taking EPT are more likely to be found when they are bigger and have spread beyond the breast.
Risk factors for ovarian cancer are harder to study because it is a less common cancer. Even when something increases the risk of developing ovarian cancer, the risk of actually getting this cancer is still likely to be low.
The WHI did not find a real difference in ovarian cancer risk with EPT. Although there were more cases of ovarian cancer in the women on EPT, this may have been due to chance because of the small number of women who were affected with this cancer.
However, a recent analysis combined the results of more than 50 studies, including randomized controlled trials and observational studies. This analysis found that women who took estrogen and progestin (progesterone) after menopause did have an increased risk of getting ovarian cancer. The risk was highest for women taking hormones, and decreased over time after the hormones were stopped.
In the WHI study of EPT, the results were mixed. Women who took EPT had a lower risk of getting colorectal cancer at all, but the cancers they got were more advanced (more likely to have spread to lymph nodes or distant sites) than the cancers in the women not taking hormones.
Some observational studies have found a lower risk of colorectal cancer in women taking EPT, but some did not. So far, though, observational studies have not linked EPT with a higher risk of colorectal cancer.
In women who still have a uterus, using systemic ET has been shown to increase the risk of endometrial cancer (cancer of the lining of the uterus). The risk remains higher than average even after ET is no longer used. Although most studies that showed an increased risk were of women taking estrogen as a pill, women using a patch or high-dose vaginal ring can also expect to have an increased risk of endometrial cancer.
Because of this increased cancer risk, women who have gone through menopause and who still have a uterus are given a progestin along with estrogen. Studies have shown that EPT does not increase the risk for endometrial cancer.
ET is not linked to a higher risk of breast cancer. In fact, certain groups of women taking ET, such as women who had no family history of breast cancer and those who had no history of benign breast disease, had a slightly lower risk of breast cancer.
However, a recent analysis combined the results of more than 50 studies, including randomized controlled trials and observational studies. This analysis found that women who took estrogen after menopause did have an increased risk of getting ovarian cancer. The risk was highest for women currently taking estrogen, and decreased over time after estrogen was stopped.
Observational studies have shown that women who take ET have a higher risk for ovarian cancer compared with women who take no hormones after menopause. The overall risk remains low, but it does increase the longer a woman uses ET. The risk of ovarian cancer goes down after a woman stops taking the hormone.
The decision to use estrogen, alone (ET) or with a progestin therapy (EPT), after menopause should be made by each woman and her doctor after weighing the possible risks and benefits. Things to think about include:
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