12-1 MAJOR OUTCOMES IN HIGH-RISK HYPERTENSIVE PATIENTS RANDOMIZED TO ANGIOTENSIN-CONVERTING ENZYME INHIBITOR OR CALCIUM CHANNEL BLOCKER VS DIURETIC
      “Thiazide-type diuretics should be considered first for pharmacologic therapy in patients with hypertension.” They are unsurpassed in lowering BP, in reducing clinical events, and in tolerability. They are much less costly.
      Since a large proportion of participants required more than one drug to control their BP, it is reasonable to infer that a diuretic should be included in all multidrug regimens.

12-2 A COMPARISON OF RATE CONTROL AND RHYTHM CONTROL IN PATIENTS WITH ATRIAL FIBRILLATION
      None of the presumed benefits of rhythm control by cardioversion were confirmed by this study.
      The strategy of restoring and maintaining sinus rhythm had no clear advantage over the strategy of controlling ventricular rate, and allowing the AF to continue.
      Patients in the cardioversion group were significantly more likely to be hospitalized and have adverse drug effects. This has some cost considerations.
      Rate control (with drugs alone) should be considered a primary approach to therapy and rhythm control (by attempted cardioversion &/or drugs), may be abandoned early if it is not fully satisfactory.
      Management of AF by conversion to sinus rhythm by drugs &/or electric shock offered no survival advantage over ventricular rate control by drugs.

12-3 THE METABOLIC SYNDROME AND TOTAL AND CARDIOVASCULAR DISEASE MORTALITY IN MIDDLE-AGED MEN
      Middle-aged men with the MET-S had an increased cardiovascular and overall mortality even in the absence of baseline diabetes and CVD. Early identification, treatment, and prevention of the MET-S presents a major challenge.
      “The importance of the metabolic syndrome from a clinical and public health perspective may be greatest in it earliest stages, before development of CVD or diabetes.”
      Modest lifestyle interventions can improve components of the MET-S.

12-4 HOT FLUSHES
      Hormone replacement therapy remains the most effective therapy by far. But some women are now reluctant to take them.
      Selective serotonin reuptake inhibitors (SSRIs) are somewhat effective, but a poor second choice.

12-5 SIGNIFICANT DIFFERENTIAL EFFECTS OF ALENDRONATE, ESTROGEN, OR COMBINATION THERAPY ON THE RATE OF BONE LOSS AFTER DISCONTINUATION OF TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS.
      At one year, accelerated bone loss was seen after withdrawal of estrogen., but not after withdrawal of alendronate or combined estrogen/alendronate therapy.
      Combined alendronate/HRT is likely more beneficial than either alone.
      Therapy to preserve BMD must be continued indefinitely.

12-6 BODY MASS INDEX AND THE RISK OF STROKE IN MEN
      Overweight and obese men were at increasing risk of stroke. The risk appeared to be independent of hypertension, diabetes, and cholesterol levels.
      Increased risk of stroke is another hazard of obesity.

12-7 SCREENING FOR PROSTATE CANCER: AN UPDATE OF THE EVIDENCE FOR THE U.S. PREVENTIVE SERVICES TASK FORCE
      Screening can detect PC earlier. A major problem is the heterogeneity of PC. The large discrepancy between PC diagnosis and deaths indicates that some, and probably most, PC detected by screening is clinically unimportant. Because precise evidence regarding the prognosis of various types of PC is lacking, the types of PC that will cause clinical symptoms and death, and that can be treated better if detected early, are not defined. The most appropriate targets of screening are not known. “Since research has not yet clearly defined the characteristics of clinically important prostate cancer, we do not know what the specific target of screening should be.”
      “The efficacy of screening for prostate cancer remains uncertain.”
      “The USPTF concludes that evidence is insufficient to determine whether the benefits outweigh the harms for a screened population.”

12-8 CORTICOSTEROID THERAPY FOR PATIENTS WITH ACUTE EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE.
      Short courses of systemic corticosteroids in acute exacerbations of COPD improve spirometric and clinical outcomes.

12-9 THYROID-HORMONE SUPPRESSIVE THERAPY IN BENIGN THYROID NODULES –IS IT EFFECTIVE?
      Despite the wide use of thyroid hormones in the treatment of thyroid nodules, there is still lack of evidence to generally justify thyroid suppression as a therapy. “It is not known If thyroid-hormone treatment is effective in controlling the size of thyroid nodules, or safe, particularly if suppression of thyroid-stimulating hormone is long-term.”

12-10 EFFECTS OF SUBCLINICAL THYROID DYSFUNCTION ON THE HEART.
      “Subclinical thyroid dysfunction is not a compensated biochemical state.” Timely treatment could help prevent cardiovascular involvement.” (Eg, judicious thyroxine replacement for high TSH states and beta-blockers for low TSH states.)

12-11 ANTIBIOTICS FOR ACUTE PURULENT RHINITIS
      Guidelines suggest that antibiotics are ineffective. This may not be true. However, the modest benefit for this condition, which is rarely life-threatening, may warrant constraint on their use because of side effects, cost, development of antibiotic resistance, and promotion of use of heath services. Perhaps they should consider delayed prescriptions in an attempt to meet demand from patients while maintaining evidence based integrity.

12-12 LOW DOSE MIFEPRISTONE AND TWO REGIMENS OF LEVONORGESTREL FOR EMERGENCY CONTRACEPTION
      Single-dose mifepristone, single-dose levonorgestrel and two-dose levonorgestrel were very efficacious and prevented a high percentage of pregnancies. There was no difference in efficacy.
      A single dose of levonorgestrel can be substituted for the two-dose regimen.
      Efficacy extends, but diminishes, for up to 5 days.

1. Multicenter, randomized, double-blind clinical trial entered over 33 000 participants age 55 and older (mean = 67). All had hypertension and at least one other CHD risk factor:
         Hypertension – stage 1(140-159/90-99) or stage 2 (160-179/100-109). “Severe” hypertension excluded. Almost all were taking antihypertension drugs. Mean BP of untreated patients at baseline = 156/90
         Other risk factors: previous myocardial infarction (MI) or stroke, left ventricular hypertrophy, type 2 diabetes, current cigarette smoking, high density cholesterol under 35 mg/dL, documented other CVD.
2. Randomized to:

   A.	Chlorthalidone (Generic) 12.5 to 25 mg daily
   B.	Amlodipine (Generic; Norvasc) 2.5 to 10 mg daily
   C.	Lisinopril (Generic; Prinivil; Zestril) 10 to 40 mg daily.

   (A 4th drug, the alpha-blocker, doxazocin (Cardura), was included in the original study. This arm of the study was terminated early because of an excess incidence of heart failure.)
3. Addition of a 2nd or 3rd drug was permitted. About 40% in each group was taking a step 2 or a step 3 drug at sometime during the observation period.
4. Followed-up frequently for 3+ years to 8 years (mean = 5 years).
5. Primary outcome = fatal CHD or non-fatal MI

1. At 5 years:

   	Chlorthalidone	Amlodipine	Lisinopril
   Systolic BP (mean mm Hg)	134	135	136
   Diastolic BP (mean mm Hg)	75	75	75
   Achieved BP goal (<140/90)	68%	66%	61%
   Cholesterol (mg/dL at 4 y)	197	196	195

         (Many were taking lipid-lowering drugs.)

   Potassium (< 3.5 mEq/L at 4 y)	9%	2%	1%
   Fasting glucose (mean mg/dL)	126	124	122
   Diabetes (FBS > 126)	12%	10%	8%

         (Given the large sample size, almost all differences in follow-up BP and biochemical measurements were statistically significant.)
2. Amlodipine vs chlorthalidone: Secondary outcomes were similar. However, the amlodipine group had a higher risk of heart failure. (10.2% vs 7.7%; absolute difference = 2.5%)
3. Lisinopril vs chlorthalidone: Higher 6-year rates of combined CVD (33.3% vs 30.9%); stroke 6.3% vs 5.6%) and heart failure (8.7% vs 7.7%). [Absolute differences 0.7% to 2.4%.]

1. Neither the di-hydropyridine calcium blocker amlodipine, nor the ACE inhibitor lisinopril, was superior to the thiazide diuretic chlorthalidone in preventing major coronary events or in increasing survival.
2. Chlorthalidone was superior to amlodipine in preventing HF.
3. Chlorthalidone was superior to lisinopril in preventing HF and aggregate cardiovascular events.
4. The chlorthalidone group had better drug tolerance and BP control.
5. The lower incidence of HF in the chlorthalidone group is consistent with previous reports.
6. No significant differences in end-stage renal disease, glomerular filtration rate, or increase in creatinine levels were noted for the lisinopril vs chlorthalidone comparisons.
7. Benefits of chlorthalidone vs the other drugs were evident despite the higher levels of cholesterol, insulin resistance, and hypokalemia.
8. In black (vs non-black patients), greater benefits were observed for combined CVD and stroke, along with a similar trend for HF. Chlorthalidone resulted in greater BP lowering in blacks.
9. A great number of patients required more than one drug.

1. Randomized trial compared the two treatment strategies in over 4000 patients (mean age 70) with a history of AF. The great majority had a qualifying episode of AF within the previous 6 weeks, most lasting over 2 days.
   The majority had recurrent AF. Some were in normal sinus rhythm at start of therapy.
2. The majority had hypertension. Many had a history of coronary disease. Left atrium was enlarged in 2/3, and left ventricular function was depressed in 26%.
3. Criteria for enrollment included the likelihood that AF would cause illness or death; long-term treatment for AF was warranted; and anticoagulant therapy was not contraindicated.
4. Randomized to:

   A.	Cardioversion attempt group (Rhythm control): The drug selected to attempt reversion to sinus rhythm was chosen by the treating physician. (Mainly amiodarone and sotalol.) Electrical cardioversion could be attempted as necessary. (Often attempted more than once.) Anticoagulation was continued in most.
   B.	Ventricular rate control group (Rate control; no attempt to convert): Drugs included beta-blockers, calcium-channel blockers, digoxin, or a combination. A combination was commonly used. Goal was heart rate no higher than 80 at rest, and no higher than 110 on a 6-minute walk. Anticoagulation was continued indefinitely.

5. Primary endpoint = death. Follow-up mean = 3.5 years.

1. Ventricular rate control group:

   Reverted to normal sinus rhythm at 5 years	35%
   (Many reverted to normal sinus rhythm while receiving rate control drugs without any attempt at cardioversion,)
   Crossed over to cardioversion attempts	12%
   Adequate rate control	80%
   Death at 5 years	21%
   Stroke (annual rate)	1%
   Hospitalizations	73%

2. Cardioversion group (Rhythm control):

   Sinus rhythm at 5 years	63%
   Crossed over to ventricular rate control	38%
   (About 1/3 failed cardioversion and were then treated with rate control.)
   Death at 5 years	24%
   Stroke (annual rate)	1%
   Hospitalizations	80%

3. In both groups, most strokes occurred in patients in whom warfarin had been stopped, or when INR became subtherapeutic.
4. Adverse events: Pulmonary events, gastrointestinal events, bradycardia, prolongation of QT interval, and “other” events prompting discontinuation of a drug were significantly more frequent in the cardioversion attempt group.

1. None of the presumed benefits of rhythm control by cardioversion were confirmed by this study. The strategy of restoring and maintaining sinus rhythm had no clear advantage over the strategy of controlling ventricular rate, and allowing the AF to continue.
2. All comparisons of subgroups according to the prespecified covariates either showed non-significant differences, or a greater benefit from ventricular rate control.
3. The cross-over rate was greater among persons originally assigned to cardioversion. Drugs aimed at converting AF to normal sinus rhythm and at sustaining normal sinus rhythm frequently fail.
4. The risk of stroke (the most serious clinical consequence of AF) was low in both groups. The majority occurred in patients who had stopped anticoagulation or in those who failed to maintain a therapeutic INR.
5. Patients in the cardioversion group were significantly more likely to be hospitalized and have adverse drug effects. This has cost considerations. The adverse effects of amiodarone, the most commonly used drug, might reasonably be expected to increase with longer use.
6. “Rate control should be considered a primary approach to therapy, and rhythm control, if used, may be abandoned early if it is not fully satisfactory.”
7. Anticoagulation should be continued even if the patient converts to sinus rhythm.

Rate control group -- received drugs to slow and control ventricular rate. No further attempts at cardioversion.
Rhythm control group -- underwent serial cardioversions and received anti-arrhythmic drugs.
Oral anticoagulation was given to both groups.

1. Population-based prospective cohort study entered over 1200 Finish men, age 42 – 60 (mean = 51) at baseline.
   None had known CVD, cancer or diabetes.
2. Determined prevalence of MET-S at baseline.
   (I abstracted data only on those defined by the NCEP definition. RTJ)
3. Determined mortality. Followed for 11 years.

1. Prevalence of MET-S ranged from 8% to 14% depending on the definition.
2. 109 deaths occurred: 46 due to CVD, 27 of which were due to coronary heart disease (CHD).
3. Men with the MET-S as defined by NCEP were 3 times more likely to die of CHD after adjustments for traditional cardiovascular risk factors.
4. Estimated overall survival at 14 years:
   90% for those without the MET-S
   79% of those with the MET-S
5. The investigators calculated the effect of other risk factors when added to those of the MET-S. Factors such as smoking, elevated LDL-cholesterol, and elevated systolic BP increased risk.

1. The increased mortality found in persons with the MET-S was independent of other important and potentially confounding risk factors.
2. The association persisted even when persons with impaired fasting glycemia were excluded. (Fasting blood glucose 100- 110 mg/dL.)
3. The prevalence of MET-S in this cohort was likely lower than will be found in the USA. It is likely that prevalence of the MET-S will increase and its disease burden will increase.
4. MET-S is associated with an increased mortality for men with MET-S even in its earlier phases, before development of CVD or diabetes.
5. Modest lifestyle interventions can have a major impact in decreasing the risk for diabetes in glucose-intolerant individuals. Physical activity, weight loss and proper diet favorably affect components of the MET-S.
6. Early identification, treatment, and prevention of the MET-S presents a major challenge.
7. “The importance of the metabolic syndrome from a clinical and public health perspective may be greatest in it earliest stages, before development of CVD or diabetes.”

1. Double-blind randomized trial entered 244 postmenopausal women (mean age = 64). All were post-hysterectomy. All had osteoporosis. (BMD at lumbar spine over 2.0 standard deviations below peak bone mass in young adults.)
2. Randomized to:
       Alendronate 10 mg daily
       Conjugated estrogen 0.625 mg daily
       Both
       Placebo
3. All took supplementary calcium.
4. After 2 years, many taking active drugs were switched to placebo. Some continued on the original drug for the 3rd year.
5. Measured BMD at 2 years and at 3 years.

1. Between-treatment differences at 3 years:

   	Lumbar spine	Total hip
   Alendronate 2y then placebo for 1 y vs placebo/placebo	+7.0%	+4.0%
   Estrogen for 2 y then placebo for 1 y vs placebo/placebo	+2.9%	+2.1%
   Alendronate + estrogen for 2 y then placebo for 1 y vs placebo/placebo	+9.5%	+3.9%
   Alendronate + estrogen for 3 y vs placebo for 3 y	+11.2%	+6.5%

   (Ie, some additional evidence that combination therapy is better than either drug alone. Also that patients who take estrogen for 2 years and then discontinue lose BMD more rapidly than those who use alendronate and then discontinue.)
2. All drugs were well tolerated.
3. No difference in clinical outcomes. (Short time period and relatively few patients.)

1. Women who took estrogen for 2 years and then discontinued lost significant amounts of BMD during the year after discontinuation. Bone loss after discontinuation of estrogen was accelerated.
2. Women who took alendronate (or alendronate + estrogen) for 2 years and then discontinued, maintained the increases in BMD.
3. Women who took alendronate + estrogen for 3 years had even greater increases in BMD.
4. The Framingham study reported that women who took estrogen during the 2 years before the study had a 66% reduction in hip fracture. The association may be only for current estrogen users. When estrogen is discontinued, BMD decreases and the protective effect is lost.

1. A prospective cohort study (The Physicians Health Study) entered over 21 000 US male physicians (mean age = 53) None had previous cardiovascular disease.
2. Mean BMI = 24.9. 57% had a “normal” weight according to WHO criteria (BMI < 25); 38% were overweight (BMI 25-30); 5% were obese (BMI > 30)
3. Determined incidence of stroke (ischemic and hemorrhagic). Evaluated association of BMI with risk of stroke.
4. Follow-up = 13 years.

1. Over the follow-up period, 747 strokes were documented: 631 ischemic, 104 hemorrhagic, 12 undefined.
2. Association with BMI:
       Mean systolic and diastolic BP and prevalence of hypertension increased with increasing BMI.
       Current smoking highest in the obese.
       Regular exercise decreased with increasing BMI.
       Leanest consumed more alcohol.
3. Age and multiple-adjusted relative risks of stroke:

   BMI	< 23	23-25	25-27	27-30	> 30
   Total stroke	1.00 (referent)	1.09	1.32	1.51	2.00
   Ischemic stroke	1.00	1.07	1.33	1.54	1.95
   Hemorrhagic	1.00	1.30	1.45	1.50	2.25

   (Compared with BMI < 23, those with BMI > 30 twice the risk of stroke.)
4. When BMI was evaluated as a continuous variable, each unit increase in BMI was associated with a 6% rise in adjusted relative risk of stroke.
5. Additional adjustments for hypertension, diabetes, and hypercholesterolemia only slightly attenuated the risks for total and ischemic strokes,.

1. Increasing BMI was associated with a steady increase in risks of total, ischemic, and hemorrhagic stroke.
2. Although concomitant hypertension and diabetes accounted for much of the increase in total and ischemic stroke, a significant increase in risk associated with increased BMI remained after adjustment for these potential biases.
3. What might the mechanism be for this independent association? Some have proposed higher levels of prothrombotic factors and increased levels of C-reactive protein
4. BMI is an imperfect measure of obesity. Abnormal regional adiposity (abdominal) may further increase risk for stroke.
5. Increased BMI is a modifiable factor.

Screening can detect PC earlier. A major problem is the heterogeneity of PC. The large discrepancy between PC diagnosis and deaths indicates that some, and probably most, PC detected by screening is clinically unimportant. Because precise evidence regarding the prognosis of various types of PC is lacking, the types of PC that will cause clinical symptoms and death, and that can be treated better if detected early, are not defined. The most appropriate targets of screening are not known.
“The efficacy of screening for prostate cancer remains uncertain.”

1. Systematic search retrieved 8 studies that met criteria for inclusion. These clinical trials were randomized and placebo-controlled. They considered effects of systemic corticosteroids in patients with acute exacerbations as well as any adverse effects.
2. Corticosteroids included methylprednisolone, prednisolone, prednisone, and hydrocortisone, given by mouth or I.V. for various times.

1. Five of the 8 studies found significant improvements in forced expiratory volume at 1 second (FEV1) of over 20%.
2. Two studies found improvement in clinically relevant outcomes.
3. One study did not find significant improvement in spirometric measures.

1. Study design factors may lead to underestimation or overestimation of steroid effect. These stem from the definition and identification of COPD and the quality and validity of outcome measures.
2. Differentiation from asthma is based on finding minimal reversible airflow obstruction. The gold standard for diagnosis of COPD is an objective measure of lung function. In the absence of spirometry, the diagnosis is usually based on historical and physical findings.
3. Most COPD exacerbations are due to worsening airflow obstruction caused by respiratory tract infections.
4. It is possible that some patients with asthma or asthma combined with COPD were included in the studies. Nevertheless, the overall implications of the reported trials remains valid. “Patients who present to their physicians with symptoms of a COPD exacerbation are likely to benefit immediately from systemic corticosteroid therapy regardless of whether their true diagnosis is COPD or asthma.”
5. In patients with an exacerbation, corticosteroid therapy modestly reduces treatment failures and duration of hospitalization, and improves FEV1. Benefit is apparent within one day and lasts for at least 5 days of therapy. \
6. The total steroid dose given to “average” patients with exacerbations probably does not carry a significantly increased risk of bone loss.

Most benign nodules exhibit a favorable prognosis.
They slowly increase in size over years.
No convincing evidence that growth may be halted by suppressive therapy.

1. Conducted a systematic review of available data on effects of subclinical hypo- and hyper-thyroidism on the cardiovascular system.
2. Subclinical hypo-thyroidism:

   A.	Definition: High thyroid stimulating hormone (TSH) with normal free thyroxine (FT4) and normal free triiodothyronine (FT3). It is associated with under-replacement of exogenous thyroxine in patients with overt hypothyroidism; a number of drugs; and thyroiditis. It is common. It predisposes to overt hypothyroidism.
   B.	Cardiac manifestations: A number of abnormalities have been described in small studies. Patients may have impaired left ventricular diastolic function at rest and systolic dysfunction on effort. This may result in poor physical exercise capacity. Some studies reported the pre-ejection period and the interval from Q wave to pulse arrival at the brachial artery were prolonged. Low aortic acceleration (index of left ventricular function) reverted to normal with thyroxine therapy. Longer peak filling rate, normalized after thyroxine therapy. (Not all studies have been duplicated; controversy persists)
   C.	Coronary artery disease: A recent study reported restoration of euthyroidism in patients with subclinical hypothyroidism reduced both total and LDL-cholesterol levels, lipoprotein(a), and homocysteine levels. (All beneficial changes.) The large Rotterdam epidemiological study reported subclinical hypothyroidism is associated with greater prevalence of aortic atherosclerosis, and myocardial infarction in elderly women.
   D.	“Subclinical hypothyroidism should be considered a mild form of thyroid failure . . . that is associated with initial signs of cardiovascular hypothyroidism.”
   E.	Benefits of thyroxine treatment include improved lipid profiles, possible lowered risk of atherosclerosis and coronary artery disease, prevention of cardiac morphologic and functional abnormalities, prevention of progression to overt hypothyroidism, a modest symptom benefit, and prevention of goiter in some patients.       The thyroxine dose must be lower than in those with overt disease. Dosage must be monitored to achieve optimal replacement dose. Aim for TSH of 1.0 to 2.0 mU/L. Start with 12.5 ug in the elderly and 25 ug in younger patients.       An interesting observation: changes in cardiovascular measures can also be found in subclinical hypothyroid patients with TSH values less than 10 mU/L. “Persistent clinical hypothyroidism with TSH values which are stable above 4.0 should be treated, particularly if associated with thyroid antibodies.

3. Subclinical hyper-thyroidism:

   A.	Definition: Low TSH (< 0.1 mU/L or undetectable) with normal FT4 and FT3. It may be due to endogenous or exogenous factors.      1) Endogenous: This may be due to early Graves disease, multinodular goiter, and an autonomously functioning thyroid nodule)      2) Exogenous: usually due to overtreatment with thyroxine. The most common cause of subclinical hyperthyroidism is thyroxine therapy. Appropriate dosage to maintain normal TSH levels is necessary to avoid adverse cardiovascular effects of mild hormone excess or deficiency.
   B.	Various cardiac abnormalities have been described: shorter isovolumetric contraction time and pre-ejection period; increased heart rate; increased number of atrial premature beats; increased left ventricular mass; impaired left ventricular diastolic function (impaired relaxation); reduced exercise performance; reduced peak workload and peak oxygen uptake; increased peak aortic flow; increased left ventricular mass; and an increase in prevalence of atrial fibrillation.
   C.	Subclinical hyperthyroidism is also associated with an increased mortality, especially from cardiovascular disease.

4. Despite the high prevalence of subclinical thyroid dysfunction in the general population, treatment of this condition is controversial. This review concluded that minimal “persistent” changes in thyroid hormone levels cause significant changes in the heart.
5. “Subclinical thyroid dysfunction is not a compensated biochemical state.” Timely treatment could help prevent cardiovascular involvement.” (Eg, judicious thyroxine replacement for high TSH states; beta-blockers or low-dose anti-thyroid drugs for low TSH states..)

1. Randomized, double blind multi-country trial entered over 4000 women. All were healthy and had regular menses. All requested EC within 120 hours of one unprotected coitus. All had a normal menstrual cycle before the current cycle. A sensitive test ruled out pregnancy. None wished to continue a pregnancy should EC fail.
2. Randomized to:
       A. 10 mg single dose mifepristone.
       B. 1.5 mg single dose of levonorgestrel.
       C. Two doses of 0.75 mg levonorgestrel 12 hours apart.
3. Primary outcome = unintended pregnancy.

1. Pregnancy rates and prevented pregnancy:

   	Number	Pregnancies	Expected pregnancies
   Mifepristone	1359	21 (1.55%)	108
   One dose levonorgestrel	1356	20 (1.47%)	111
   Two dose levonorgestrel	1356	24 (1.77%)	106

2. Delay in treatment after intercourse:
       1 – 3 days –79% to 82% of expected pregnancies prevented.
       4 – 5 days – 60% to 63% of expected pregnancies prevented.
          (This extends the protective period to 5 days, although efficacy diminishes with time.)
3. Adverse effects: Nausea occurred in 15% and vomiting in 1% of groups; diarrhea in 3% to 5%.     (No significant difference between groups.) Fatigue, dizziness headache, lower abdominal pain, and breast tenderness reported in up to 15% with no differences between groups. Lower abdominal pain occurred in 31% of the levonorgestrel groups and in 19% of the mifepristone group. Delay in menses occurred in 9% of mifepristone group, slightly more frequent than the other 2 groups. Bleeding within the first week occurred in 19% of the mifepristone group and in 31% of the levonorgestrel groups.
4. Many more women in developed countries reported side effects than in developing counties. (This is certainly a provocative comment. RTJ)

1. There was no significant difference in efficacy between the 3 regimens.
2. Mifepristone delays ovulation. This results in a longer cycle and later return of menses. A delay in menses adds to anxiety. There is a continued risk of pregnancy if women have unprotected coitus after mifepristone as compared with levonorgestrel.
3. The levonorgestrel dose need not be split. A single dose simplifies treatment and does not increase side effects.
4. Although efficacy declines, EC still prevented a high percentage of pregnancies for up to 5 days.