RESEARCH HIGHLIGHTS Spironolactone and Hyperkalemia

RESEARCH HIGHLIGHTS

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and safety of DES (with sirolimus or paclitaxel) patients with heart failure who were treated GLOSSARY and BMS. All trials provided 6–12 months' clini- with ACE inhibitors, there were 560 additional ECG Electrocardiogram cal follow-up after index PCI. Using a hierarchi- hospitalizations for hyperkalemia (95% CI 285 cal Bayesian random-effects model, the team to 754) and 73 additional inpatient deaths pooled the results, stratifying by the type of (95% CI 27 to 120) in 2001, compared with the drug and presence of carrier polymer. expected numbers. The pooled results indicated that mortality In conclusion, publication of RALES was and MI occurred at similar rates for DES and associated with a sharp increase in the spironol- BMS. Major cardiac adverse events, however, actone prescription rate, in the rate of hospi- occurred at a lower rate in the DES group than talization for hyperkalemia and in associated in the BMS patients (7.8% vs 16.4%; odds mortality. The authors suggest that clinicians ratio (OR) 0.42; 95% credible interval (CI) 0.32 should take into account other risk factors for to 0.53), as did angiographic restenosis (8.9% hyperkalemia when prescribing spironolactone, vs 29.3%; OR 0.18; 95% CI 0.06 to 0.40). and that renal function and potassium levels The authors conclude that sirolimus-eluting should be closely monitored. and polymeric-paclitaxel-eluting stents are superior to BMS in reducing the rates of angio- Original article Juurlink DN et al. (2004) Rates of hyperkalemia after publication of the randomized aldactone graphic restenosis and major cardiac adverse evaluation study. N Engl J Med 351: 543–551 events, although no clear benefit has been shown in terms of a reduction in mortality or MI rates. Prediction of outcome in Original article Babapulle MN et al. (2004) A hierarchical myocardial ischemia Bayesian meta-analysis of randomised clinical trials of drug-eluting stents. Lancet 364: 583–591 A report by Mueller and colleagues has provided new information about the prognostic value of the admission ECG in cases of myocardial ischemia. Spironolactone and hyperkalemia The study included a cohort of 1,450 consecutive patients with unstable angina/non-ST-segment The landmark Randomized Aldactone Evaluation elevation myocardial infarction (nonSTEMI), who Study (RALES), published in 1999, showed that were assessed by coronary angiography within spironolactone, a potassium-sparing diuretic, 24 h of admission. Patients were divided into improves outcomes in patients with severe three groups according to the presence of new heart failure. The drug can sometimes cause ST-segment depression (n = 136), T-wave inver- life-threatening hyperkalemia, however, when sion (n = 419) or no changes on the admission used in combination with angiotensin-convert- ECG (n = 895). Revascularization was carried out ing enzyme (ACE) inhibitors (which are also in the majority of patients (n = 1,066), most often indicated for heart failure). Although this com- by percutaneous coronary intervention (PCI) with plication was rare in RALES, it is possible that stent placement. Coronary artery bypass grafting physicians prescribe spironolactone more freely was carried out in selected patients. The primary in practice. Juurlink et al. have carried out a time- endpoint was all-cause mortality. series analysis to examine the effects of RALES Adjusting for potential confounders, the cumu- at the population level in Ontario, Canada. lative death rate at 36 months was significantly For the period 1994–2001, the investigators higher for patients with ST-segment depression linked the records of all prescription drugs (hazard ratio [HR] 2.2, 95% CI 1.1 to 4.6) than dispensed and all hospitalizations for over for patients with no ECG changes; by contrast, 1.3 million patients aged 66 years or older. They T-wave inversion was associated with a more examined trends in spironolactone-prescribing favorable outcome (HR 0.44, 95% CI 0.20 to rates, hospitalization for hyperkalemia and 0.96). Surprisingly, the prognostic value of these associated mortality. ECG changes was similar in men and women. From 1994 to 2001, there was a statisti- Mueller et al. conclude that ST-segment cally significant increase (P < 0.001) in rates of depression and T-wave inversion were impor- spironolactone prescription, hospitalization for tant prognostic factors in patients undergoing hyperkalemia and associated mortality. Among very early revascularization for unstable angina/

NOVEMBER 2004 VOL 1 NO 1 NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE 5