2-1 ACCURACY OF OTTAWA ANKLE RULES TO EXCLUDE FRACTURES OF THE ANKLE AND MID-FOOT

1) Inability to bear weight and walk 4 steps immediately after the injury, or on presentation to the emergency department.
2) Bony tenderness localized to the posterior edge (and up to 6 cm above) either malleolus (four spots). Fewer than 2% of patients negative for fracture by the rules actually had fracture.
Application of the rules greatly reduces the number of X-rays taken.

2-2 A COMPARISON OF OUTCOMES WITH ANGIOTENSIN-CONVERTING-ENZYME INHIBITORS AND DIURETICS FOR HYPERTENSION IN THE ELDERLY.
      Initiation of antihypertension treatment with ACE inhibitor in older men appeared to lead to better outcomes than diuretics despite similar reductions of BP. Patients often required 2 or more drugs.
      NNT to benefit one male patient over 1 year = 270. No benefit in females.

2-3 INITIAL TREATMENT OF HYPERTENSION
      On the basis of available data, diuretics or beta-blockers remain appropriate for the initial treatment of uncomplicated hypertension.
      �In patients over age 65, morbidity and mortality from cardiovascular disease are reduced when systolic blood pressure is lowered to a level below 160 mm Hg. Whether levels below 140 mm Hg provide additional protection is unclear.� �Optimal blood pressure targets remain to be determined, particularly for elderly patients.�
      Primary care clinicians should develop a set initial drug protocol for treating long standing (ie, lifetime) illnesses which require long-term costly medication. We should aim to provide the least expensive, least toxic drugs and drug doses, which are easiest to take, and more likely to lead to compliance. The editor of Practical Pointers suggests a protocol.

2-4 THE PREVENTION AND TREATMENT OF JET LAG.
      The Cochrane Review concludes that 2 to 5 mg melatonin taken at bedtime at the new destination is effective, and may be worth repeating for the next two to four days.
      The article gives other suggestions for minimizing both travel fatigue and jet lag.

2-5 EFFECT OF IBUPROFEN ON CARDIOPROTECTIVE EFFECT OF ASPIRIN
      Ibuprofen negates the protective effect of low dose aspirin. Use another NSAID.

2-6 ADDING A TEST FOR HUMAN PAPILLOMA VIRUS DNA TO CERVICAL-CANCER SCREENING
      Virtually all squamous-cell cervical carcinomas contain one of eighteen types of human papilloma virus (HPV). The relative risk of cervical cancer associated with persistent infection with high-risk types of HPV (especially types 16 and 18) is higher than the risk of lung cancer associated with smoking.
      The discovery that continued presence of tumor-producing HPV is necessary for development of cervical cancer is revolutionizing our approaches to screening and prevention. An obvious corrrelary is that the absence of infection means that the risk of cervical cancer is negligible.

2-7 COMBINED SALMETEROL AND FLUTICASONE IN THE TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
      Combined inhaled long-acting beta agonist/corticosteroid produced better control of symptoms and lung function than the use of either component alone, with no greater risk of adverse effects.
      �This combination treatment should be considered for patients with COPD.�

2-8 ALCOHOL CONSUMPTION AND RISK OF STROKE: A Meta-analysis
      Heavy alcohol consumption increases risk of stroke. Light-to-moderate consumption protects against ischemic stroke, but not against hemorrhagic stroke.

2-9 EFFECTS OF INITIATING CARVEDILOL IN PATIENTS WITH SEVERE CHRONIC HEART FAILURE
      Benefits of beta-blocker therapy with carvedilol were evident within a few weeks in patients with advanced HF who were euvolemic. Benefits were similar to those obtained by long-term therapy.
      Initiation of treatment was well tolerated when a go-slow, go-low dose was used.

2-10 ASSOCIATION OF SERUM DIGOXIN CONCENTRATION AND OUTCOMES IN PATIENTS WITH HEART FAILURE
      Higher serum concentrations of digoxin were associated with increased mortally in patients with HF who were in normal sinus rhythm. The most effective concentration may be 0.5 to 0.8 ng/mL .

2-11 CARDIAC RESYNCHRONIZATION AND DEATH FROM PROGRESSIVE HEART FAILURE
      Recently, cardiac pacemakers have been modified to correct ventricular dyssynchrony (left bundle branch block). The new pacemakers use a left ventricular lead that ensures stimulation of the left ventricle at, or near, the time of right ventricular depolarization. Synchronization enhances cardiac function and reduces myocardial oxygen consumption. It improves exercise capacity, functional class, and quality of life.
      Use of the pacemaker was associated with a reduction in mortality from 3.5% to 1.7% over 6 months among patients with advanced HF.

2-12 PANEL INDORSES LIMITED ROLE FOR CRP TESTS
      C-reactive protein (CRP) has emerged as the leading inflammatory marker for cardiovascular disease.
      Does the test add anything to the list of risk markers now available? How should it be used?
      A guideline suggests that CRP has its greatest utility in people deemed at intermediate risk of CVD. (intermediate risk = 10% to 20% risk of developing CVD in the next 10 years as calculated from the Framingham risk score.) Physicians should assess traditional risk factors and calculate the absolute Framingham risk score before testing with CRP. http://hin.nhlbi.nih.gov/atpiii/calcualtor.asp?usertype=prof .
      CRP should not be used routinely, or as an alternative to traditional risk factor assessment. It is not known if an elevated CRP as the sole risk marker needs treatment.

1) Inability to bear weight and walk 4 steps immediately after the injury, or on presentation to the emergency department.
2) Bony tenderness localized to the posterior edge (and up to 6 cm above) either malleolus (four spots).

3) Inability to bear weight and walk 4 steps immediately after the injury, or on presentation to the emergency department.
4) Tenderness of the navicular area or base of the 5th metatarsal.

1. Systematic review of the literature included 27 relevant studies (over 15 000 patients).

1. If the patient actually has a fracture, in how many would the tests be positive (true positive test) and in how many would the tests be negative (false negative test)? (Ie, what is the sensitivity of the test?)
   Among all who had a fracture, 96.4% to 99.6% had a positive test (true positive).
   Sensitivity of the test in determining fracture = 96% to 99%.
   Only 0.4% to 3.6% of patients with fracture had a negative test (false negative). Ie, very few fractures would be missed if the patient was able to walk and had no tenderness.
2. If the patient did not have a fracture, in how many would the test be negative (true negative test)? (Ie, what is the specificity of the test?)
   Among all who did not have a fracture, the studies reported a wide range of true negative tests.
   Specificity ranged from 48% to 26%.
   The investigators were surprised at the wide variability . This would indicate that, among those who did not have a fracture, many had positive test (false positive). This could indicate a high number of unnecessary X-rays would be performed. The subtlety of palpation technique might explain some of the large variation.
3. Assuming the probability of fracture overall in the cohort of patients presenting with acute ankle injury is less than 15%, fewer than 2% of those with a negative test would have a fracture.

1. Fewer than 2% of patients negative for fracture by the rules actually had fracture.
2. The rule was developed to avoid unnecessary radiography. However, the investigators recognize that use of the test may not change clinical behavior. Clinicians aim to minimize the number of missed fractures (defensive medicine) and would therefore maximize the use of X-ray in order to avoid missing one fracture. Immediate access to X-ray may further trigger requests for X-ray.

      � An unselective policy has resulted in inestimable numbers of unnecessary exposures to radiation for little diagnostic yield. In addition to being poor medicine, such profligacy is a luxury that is no longer acceptable in any health system.�
      In some studies the rules have been 100% accurate, and reduced the number of radiographs by up to 29% without missing any clinically significant fracture.

1. Prospective, randomized, open-label trial entered over 6000 subjects with hypertension (age 65 to 84; mean = 72). All were hypertensive (mean BP = 168/91). All were receiving care in family practices. None had recent cardiovascular events.
2. Assigned by randomization to: 1) ACE inhibitor based drug therapy, or 2) diuretic based therapy. The ACE inhibitor enalapril (Vasotec; generic) and the diuretic hydrochlorothiazide (generic) were recommended as initial therapy, but the specific agent and dose was decided by the family practitioner.
3. At randomization, 83% of subjects in both groups began to receive the designated therapy. At end of study, 62% to 65% were still receiving the assigned therapy; 66% were receiving mono-therapy; up to 6% were receiving three or more drugs.
4. Outcomes: total number of cardiovascular events or death from any cause.
5. Follow-up = mean of 4 years.

1. At end of study, BP declined by 26/12 mm Hg in both groups. Declines were similar in men and women.
2. Cardiovascular events and deaths per 1000 patients years:

   ACE group	56.1
   Diuretic group	59.8

   [Hazard ratio = 0.89 favoring ACE. Absolute difference = 0.37 per 100 persons per year.
   NNT(for one year to benefit one patient) = 270
3. Among male patients, the benefits were slightly more evident (hazard ratio favoring ACE = 0.83). There was no benefit for women (hazard ratio = 1.00)
4. A similar number of strokes occurred in each group.

1. This study was confined to persons mean age 72 with hypertension (mean BP = 168/91) who were relatively healthy at baseline.
2. Over 4 years, ACE inhibitor therapy was associated with fewer deaths than diuretic therapy only in male subjects; not in females. BP reductions were the same in both groups.
3. Only 60% of subjects continued to receive the drug assigned at baseline. About 1/3 of subjects required 2 or more drugs to reach target BP.
4. The study was conducted in family practices where most elderly receive their care.

Hydrochlorothiazide 50 mg	24 cents each	Pill-cut to 25 mg	12 cents each
Amiloride 5 mg/HCTZ 50 mg	20 cents each	Pill cut to 2.5/25	10 cents each.
Captopril 25 mg	20 cents each
Captopril 50 mg	20 cents each	Pill cut to 25 mg	10 cents each.

      �For patients with essential hypertension, but without complications, it makes sense for the prescribing physician to choose a diuretic in a dose that does not cause potassium wasting, precipitate gout, or have other unwanted effects.�
      �Both ACE inhibitors and diuretics are extremely effective in improving clinical outcomes.�
      It is likely that a second drug will be needed to reach target BP. As a second drug��An ACE makes sense�.
      ACE inhibitor: for patients with co-existing conditions, common in the elderly, ACE may be a first-line drug: diabetes, heart failure (combined with a diuretic), history of myocardial infarction.
      Beta-blocker: first line for angina pectoris, heart failure, history of myocardial infarction.
      Calcium blocker: first line for angina pectoris,
      Choose a combination of drugs for which there is strong evidence of effectiveness with the type of problem found in the patient.

Hydrochlorothiazide 12.5 mg; increase to hydrochlorothiazide 25 mg
Add atenolol 25 mg; increase to 50 mg
Add captopril 12.5 mg; increase to 25 mg

Hydrochlorothiazide 12.5 mg; increase to hydrochlorothiazide 25 mg
Add atenolol 25 mg; increase to 50 mg
Add captopril 12.5 mg; increase to 25 mg
(Systolic hypertension occurs most often in the elderly. Go slow; don�t push dose.)

Diabetes; Glucose intolerance

Captopril 12.5 mg; increase to 25 mg
Add hydrochlorothiazide 12.5 mg; increase to hydrochlorothiazide 25 mg
Add atenolol 25 mg; increase to 50 mg

History of myocardial infarction

Captopril 12.5 mg; increase to 25 mg
Plus atenolol 25 mg; increase to 50 mg
Add hydrochlorothiazide 12.5 mg; increase to hydrochlorothiazide 25 mg

Heart failure and left ventricular dysfunction.

Captopril 12.5 mg; increase to 25 mg
Plus atenolol 25 mg; increase to 50 mg
Plus hydrochlorothiazide 12.5 mg; increase to hydrochlorothiazide 25 mg

Kidney disease (diabetic and non-diabetic)

Captopril 12.5 mg; increase to 25 mg
Add hydrochlorothiazide 12.5 mg; increase to hydrochlorothiazide 25 mg
Add atenolol 25 mg; increase to 50 mg

      After a flight to the west, stay awake as long as it is daylight at the new destination and try to sleep when it gets dark.
      After a flight to the east, try to be awake when it is morning in the new destination, but avoid bright light in the morning and be outdoors as much as possible in the afternoon.
      (These measures will help readjust the body�s own melatonin secretion to the new day-night time.)
      Other helpful measures include: eating modestly at the times corresponding to one�s usual mealtimes; taking comfortable exercise; seeing favorite sights at times of bright light.
      Whether alcohol or caffeine affect adaptation is not clear. It probably depends on what the individual is used to. They seem more likely to hinder than help.
      What about short-acting hypnotics? They induce sleep, but do not shift the circadian phase.
      What about melatonin?

      Taken at bedtime it shifts the phase and has hypnotic effect, but the importance of these two effects has not been established. A recent Cochrane Review found 10 randomized trials comparing melatonin with placebo in long distance travelers. Eight trials found a clear reduction in jet lag associated with melatonin. Five trials which reported global jet lag scores between zero [none] and 100 [extreme] found a mean score after placebo of 48, and after melatonin 25. One study reported that as many as one in two individuals using melatonin may benefit. It may be that not all symptoms of jet lag change at the same time and severity of symptoms may depend on the time of day they are assessed.
      Adverse effects of melatonin are rarely reported. Two contraindications are in persons with epilepsy and those taking warfarin. It is freely sold in health food stores as a �dietary supplement�. There are no standards of purity. Four of six melatonin products bought in the USA were found to contain unidentified impurities. �It seems advisable to buy it from a large reputable pharmacy chain and hope for the best.� The internet offers a grey or black market.
      The Cochrane Review concludes that 2 to 5 mg melatonin taken at bedtime at the new destination is effective, and may be worth repeating for the next two to four days together with the non-drug measures noted above.

1. Divided over 7000 patients who were discharged from the hospital with a diagnosis of cardiovascular disease (CVD) and given a prescription for: 1) low-dose aspirin alone, 2) aspirin + ibuprofen, 3) aspirin + diclofenac, or 4) aspirin + any other NSAID.
2. Outcomes: All-cause mortality and cardiovascular mortality related to each of the 4 groups.
3. Follow-up = 8 years.

1. Patients in the aspirin + ibuprofen group had a significantly higher risk of all-cause mortality and CVD mortality than those in the other groups. The increased risk was clinically significant.
2.  

   Mortality per 1000 person-years.	All-cause mortality	CVD mortality
   Aspirin alone	86	59
   Aspirin + ibuprofen	98	62

3. Adding ibuprofen to aspirin was associated with one more all-cause death every year among 83 patients, and in one more cardiovascular disease death every year among 333 patients. NNT (harm) = 83; NNT(harm) = 333
4. Risk did not differ significantly between aspirin alone and the other 2 groups. (Ie, diclofenac and other NSAIDs did not interfere with aspirin�s protective effect.)

1. This lends support to the hypothesis that ibuprofen given to patients receiving low-dose aspirin for secondary prevention of CVD may negate the protective effects of aspirin, possibly by antagonizing the cardioprotective effects of aspirin.

1. Multicenter, randomized, double-blind placebo-controlled parallel-group trial followed over 1400 out-patients with COPD. All had 1) baseline forced expiratory volume in one second (FEV₁)before bronchodilation between 25% and 70% of predicted and 2) an increase of less than 10% of predicted FEV₁ 30 min after inhaling 400 mcg salmeterol, and 3) a prebronchodilator FEV₁/forced vital capacity ratio of 70% or less. All had at least a 10 pack-years of smoking and at least one episode of an acute COPD exacerbation per year for the past 3 years, and at least one exacerbation in the year preceding the study which required treatment with oral corticosteroids, antibiotics, or both.
2. Randomized to:
         1) Salmeterol (Serevent) 50 mcg and fluticasone (Flovent) 500 mcg twice daily,
         2) Salmeterol alone
         3) Fluticasone alone, or
         4) Placebo.
3. Primary endpoint was change in FEV₁.
4. Follow-up = 12 months

1. All 3 active treatments improved lung function, symptoms, and health status. And reduced use of rescue medication and frequency of exacerbations.
2. Combination treatment improved FEV₁ significantly more than placebo or the other two drugs used alone compared with placebo:

   Combined	+ 133 mL:
   Salmeterol alone	+ 73 mL
   Fluticasone alone	+ 95 mL

   (Benefits were evident at 2 weeks and were sustained throughout treatment.)
3. The differences in FEV₁ between treatment groups was unaffected by whether the participant continued to smoke. (Indeed, only 6% to 7% of participants changed their smoking habits.)
4. Exacerbations fell by 25% in the combination group vs 20% and 19% in the other treatment groups, as compared with placebo. And requirements for oral corticosteroids fell by 39%, 29% and 34% compared with placebo.
5. Treatment effect was greatest in patients with more severe disease.
6. Combination treatment produced a clinically significant improvement in health status (by a health status score) and the greatest reduction in daily symptoms.
7. All treatments were well tolerated, with no difference in frequency of adverse events, bruising, or clinically significant fall in serum cortisol concentration.

1. Combination treatment produced clinical benefits across a range of endpoints.
2. Combination treatment produced a significantly greater improvement in FEV₁.

The patients evaluated in the study were selected for their lack of reversibility. (less than 10% improvement in FEV₁ by beta agonist). This was an attempt to exclude any subject who might have had asthma, despite recent studies which suggest that most patients with COPD have at least a limited degree of reversibility. The study therefore specifically evaluated the group least likely to show improvement.

1. Systematic search found 35 relevant observational studies.
2. Used pooled data from individual studies to determine risk of stroke according to the amount of alcohol consumed. Abstinence was used as the reference group.

1. Consumption of more than 60 g alcohol per day was associated with increased risk of total stroke, ischemic stroke, and hemorrhagic stroke. (Relative risks = 1.6, 1.4, and 2,2.)
2. Consumption of less than 12 g per day was associated with reduced risk of total stroke and ischemic stroke (RR = 0.83 and 0.80)
3. Consumption of 12 to 24 g per day was associated with a reduced risk of ischemic stroke (RR = 0.7.2 )
4. There was a non-linear association between quantity of alcohol consumed and risk of ischemic stroke. A �J shaped� curve indicated that, compared with abstinence, light to moderate consumption of alcohol reduced risk.
5. There was, however, a linear relationship between alcohol consumption and hemorrhagic stroke. (Ie, no protective effect at any level of consumption.)

1. This meta-analysis found a protective effect of light-to-moderate alcohol consumption on ischemic stroke; not on hemorrhagic stroke.
2. The authors suggest several mechanisms for the protective effect on ischemic stroke: increase in HDL-cholesterol; increased fibrinolytic activity; decreased platelet activity. (Ie, an anticoagulant effect.)
3. �Any advice regarding the consumption of alcohol should be tailored to the individual patient�s risks and potential benefits.�

1. Multicenter, randomized, double-blind, placebo-controlled trial followed over 2200 patients. All had symptoms of HF at rest or with minimal exertion. All were clinically euvolemic at baseline. Mean ejection fraction was less than 25%.
2. All were treated with a diuretic, dose adjusted to minimize the degree of volume retention. Most received an ACE inhibitor or an angiotensin II blocker. Other medications continued as usual.
3. Randomized to: 1) carvedilol 3.125 mg twice daily, or 2) placebo. Dose gradually increased (6.25 mg, 12,5 mg, and then 25) at 2-week intervals to a target dose of 25 mg twice daily. The added dose was administered only if the drugs were being well tolerated.
4. A subset of very high risk patients with left ventricular ejection fractions less than 15% and more acute symptoms, including current hospitalization, was randomized separately.
5. Followed for outcomes and withdrawals during the first 8 weeks.

1.  

   Outcomes at 8 weeks	Carvedilol (N = 1133)	Placebo (N = 1156)
   Death	19	25
   Death or hospitalization	134	153
   Death, hospitalization, or withdrawal	162	188 (NNT = 50)

2.  

   Outcomes for high risk patients	(N = 308)	(N = 316)
   Death	3	15
   Death or hospitalization	44	63
   Death, hospitalization, or withdrawal	51	76 (NNT = 12)

3. �High risk� patients (with recent or recurrent decompensation or with a very depressed left ventricular ejection fraction) received even more benefits than average risk patients.
4. At 8 weeks, 59% of the carvedilol patients were receiving 25 mg twice daily.
5. Significant differences in outcomes began to appear as early as 14 to 21 days.
6. There was no difference between placebo and carvedilol in the number of patients withdrawn due to worsening HF. (5.1% vs 4.4%)
7. Dizziness, hypotension, edema, and bradycardia were more common in the carvedilol group. The investigators did not consider these serious adverse effects.

1. During both initiation and up-titration, patients treated with carvedilol had no increase in the risk of worsening HF, pulmonary edema, cardiogenic shock, or other serious adverse cardiovascular events, including death.
2. Other adverse effects (eg, dizziness and hypotension) were mild¹ and infrequent, and not considered serious.
3. This study challenges the belief that the benefits of beta-blockade in patients with HF are delayed. The ability of carvedilol to produce beneficial effects early during the course of treatment was particularly striking among patients with recent decompensation and very low ejection fractions.
4. Benefits were evident at about day 21, a time when patients were generally receiving only 6.25 mg twice daily.
5. Note that the investigators were highly experienced in treatment of HF. Patients were followed closely. They were made clinically euvolemic at onset, and every effort was made to maintain euvolemia.

1. The DIG trial in 1997 randomized over 3700 men with HF to 1) digoxin or 2) placebo. All subjects had HF with a left ventricular ejection fraction under 45%. All were in sinus rhythm.
2. This study, a post hoc analysis of the DIG trial, divided patients who received digoxin into 3 groups according to their serum digoxin concentrations at one month: 0.5 to 0. 8 ng/mL; 0.9 to 1.1 ng/mL; and 1.2 ng/mL and above.
3. Main outcome measure = all cause mortality at a mean of 37 months follow-up.

1. Higher serum concentrations were associated with increased crude all-cause mortality during follow-up:

   0.5 to 0.8 ng/ml	30%
   0.9 to 1.1 ng/mL	39%
   1.2 ng/mL and above	48%

2. Patients with concentrations of 0.5 to 0.8 ng/ml had a 6% lower mortality than patients receiving placebo. NNT(3 years to benefit one patient) = 16.
3. Patients with higher concentrations had a 3% to 12% higher mortality than those receiving placebo.
4. The association persisted after multivariable adjustments.

1. Effectiveness of digoxin varied according to serum concentrations. Higher concentrations were associated with higher mortality.
2. The previously accepted concentrations of 1.2 ng/mL and higher maybe harmful, and the currently recommended therapeutic concentrations of approximately 1.0 ng/mL may not provide any clinical benefit compared with placebo.
3. A concentration of 0.5 to 0.8 ng/mL likely constitutes the optimal therapeutic range.
4. Higher concentrations may reflect inotropic-associated increase in oxygen consumption and arrhythmias. The association between serum levels and patient outcomes may reflect the dissociated neurohormonal and inotropic effects of digoxin observed at different concentrations. Neurohormonal modulation is believed to contribute to digoxin�s symptomatic benefits among patients with stable HF who are in sinus rhythm. In contrast, digoxin-associated harms are believed to reflect inotropic-associated increases in myocardial oxygen consumption and arrhythmogenesis as serum concentrations rise to a higher level. The findings are consistent with the hypothesis that, at lower serum concentrations, digoxin provides a neurohumoral benefit without increasing inotropic-associated risk. As serum concentrations increase, the inotropic action of digoxin begins to offset the therapeutic benefits provided by neurohumoral modulation and may account for the increased risk of higher concentrations.
5. Beta-blockers were not a part of the study, making it unclear whether the outcomes would be altered by beta-blocker therapy.
6. The data provide consideration of lower target serum concentrations in patients with stable heart failure and sinus rhythm.

1. Systematic search selected 4 randomized trials of over 1600 patients. (Ages 63 to 66) Mean left ventricular ejection fraction ranged from 21% to 23% (functional class III and IV). QRS duration was prolonged in all, the majority due to left bundle branch block. All had the new pacemakers installed.
2. The great majority of patients were receiving ACE inhibitors. Some were receiving beta-blockers.
3. Randomized to: 1) Resynchronization on , or 2) Resynchronization off.
4. Follow-up = 3 to 6 months.

1. Outcomes at 3 to 6 months:

   	Resynchronization (N = 809)	No resynchronization (N = 835)
   Death from progressive HF	14 (1.7%)	29 (3.5%)
   Non-HF deaths	26	23
   All-cause deaths	40	52

2. Absolute reduction in death from progressive HF = 1.8%; NNT(6 months to benefit one patient) = 55.
3. Hospitalizations for HF were also reduced (13% vs 17%). Absolute reduction = 4%; NNT = 25.

1. This study extends the benefits of resynchronization from the previously noted improvements in exercise capacity, functional class, and quality of life, to a benefit in length-of-life. �This finding is important because approximately one half of all deaths among patients with severe heart failure results from progressive cardiac dysfunction.�
2. The characteristics of patients in these trials are typical of about 10% of heart failure patients. The number of such individuals in the population may approximate 500 000. Economic benefits may be substantial.
3. The benefits of resynchronization are biologically plausible, given the improvement in cardiac function, and improvement in exercise capacity, functional class, and quality-of-life.
4. Long-term beta-blocker therapy is associated with a similar reduction in death from worsening HF. �Cardiac resynchronization may allow enhancement of beta-blocker therapy in patients with heart failure by prevention of bradycardia.�
5. �We found a 51% relative reduction in death from progressive heart failure among 1634 patients randomized to cardiac resynchronization vs control� �We found an encouraging . . . 23% relative reduction in all-cause mortality among patients treated with cardiac resynchronization vs controls.� ¹
6. The relatively short observation period (3 to 6 months) does not permit assessment of long-term benefits. However, uncontrolled evidence showed that resynchronization was well tolerated after 2 years.